Role of miRNA in the regulatory mechanisms of estrogens in cardiovascular ageing

Oxidative Medicine and Cellular Longevity

Volumn 2018, Issue , 2018, Pages

  Pérez Cremades, Daniel ^a   Mompeón, Ana ^a   Vidal Gómez, Xavier ^a   Hermenegildo, Carlos ^a   Novella, Susana ^a  

^a UNIVERSITY OF VALENCIA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CARDIOLOGY; DISEASES; HORMONES; MAMMALS; RNA; TRANSCRIPTION;

CARDIO-VASCULAR DISEASE; CARDIOVASCULAR FUNCTION; DEVELOPED COUNTRIES; ESTROGEN RECEPTOR; PROTEIN-CODING GENES; REGULATORY MECHANISM; TRANSCRIPTIONAL LEVELS; VASCULAR EFFECTS;

GENE EXPRESSION REGULATION;

ESTROGEN; MICRORNA; MICRORNA 106; MICRORNA 125; MICRORNA 126; MICRORNA 143; MICRORNA 144; MICRORNA 145; MICRORNA 146A; MICRORNA 203; MICRORNA 21; MICRORNA 22; MICRORNA 221; MICRORNA 222; MICRORNA 23A; MICRORNA 30; MICRORNA 34; UNCLASSIFIED DRUG;

AGE; AGING; CARDIOVASCULAR DISEASE; CARDIOVASCULAR FUNCTION; ESTROGEN ACTIVITY; FEMALE; GENE EXPRESSION; HUMAN; NONHUMAN; REGULATORY MECHANISM; REVIEW; SEX DIFFERENCE; ANIMAL; BIOSYNTHESIS; GENE EXPRESSION REGULATION; METABOLISM; PATHOLOGY;

AGING; DISEASES; GENES; HEALTH; HORMONES; MAMMALS; NUCLEIC ACIDS;

AGING; ANIMALS; CARDIOVASCULAR DISEASES; ESTROGENS; GENE EXPRESSION REGULATION; HUMANS; MICRORNAS;

EID: 85060382366     PISSN: 19420900     EISSN: 19420994     Source Type: Journal    
DOI: 10.1155/2018/6082387     Document Type: Review

References (202)

1. C. S. Hayward, R. P. Kelly, and P. Collins, “The roles of gender, the menopause and hormone replacement on cardiovascular function,” Cardiovascular Research, vol. 46, no. 1, pp. 28–49, 2000.
2. M. E. Mendelsohn and R. H. Karas, “The protective effects of estrogen on the cardiovascular system,” The New England Journal of Medicine, vol. 340, no. 23, pp. 1801–1811, 1999.
3. T. S. Mikkola, M. Gissler, M. Merikukka, P. Tuomikoski, and O. Ylikorkala, “Sex differences in age-related cardiovascular mortality,” PLoS One, vol. 8, no. 5, article e63347, 2013.
4. C. Vitale, M. E. Mendelsohn, and G. M. C. Rosano, “Gender differences in the cardiovascular effect of sex hormones,” Nature Reviews. Cardiology, vol. 6, no. 8, pp. 532–542, 2009.
5. V. M. Miller and S. P. Duckles, “Vascular actions of estrogens: functional implications,” Pharmacological Reviews, vol. 60, no. 2, pp. 210–241, 2008.
6. J. A. Simon, J. Hsia, J. A. Cauley et al., “Postmenopausal hormone therapy and risk of stroke: the Heart and Estrogen-Progestin Replacement Study (HERS),” Circulation, vol. 103, no. 5, pp. 638–642, 2001.
7. J. E. Rossouw, R. L. Prentice, J. E. Manson et al., “Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause,” JAMA, vol. 297, no. 13, pp. 1465–1477, 2007.
8. T. B. Clarkson, G. C. Melendez, and S. E. Appt, “Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future,” Menopause, vol. 20, no. 3, pp. 342–353, 2013.
9. C. López-Otín, M. A. Blasco, L. Partridge, M. Serrano, and G. Kroemer, “The hallmarks of aging,” Cell, vol. 153, no. 6, pp. 1194–1217, 2013.
10. J. M. Ordovás and C. E. Smith, “Epigenetics and cardiovascular disease,” Nature Reviews. Cardiology, vol. 7, no. 9, pp. 510–519, 2010.
11. W. S. Post, P. J. Goldschmidt-Clermont, C. C. Wilhide et al., “Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system,” Cardiovascular Research, vol. 43, no. 4, pp. 985–991, 1999.
12. J. Kim, J. Y. Kim, K. S. Song et al., “Epigenetic changes in estrogen receptor β gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence,” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1772, no. 1, pp. 72–80, 2007.
13. D. S. Bendale, P. A. Karpe, R. Chhabra, S. P. Shete, H. Shah, and K. Tikoo, “17-β Oestradiol prevents cardiovascular dysfunction in post-menopausal metabolic syndrome by affecting SIRT1/AMPK/H3 acetylation,” British Journal of Pharmacology, vol. 170, no. 4, pp. 779–795, 2013.
14. D. P. Bartel, “MicroRNAs: genomics, biogenesis, mechanism, and function,” Cell, vol. 116, no. 2, pp. 281–297, 2004.
15. C. Catalanotto, C. Cogoni, and G. Zardo, “MicroRNA in control of gene expression: an overview of nuclear functions,” International Journal of Molecular Sciences, vol. 17, no. 10, p. 1712, 2016.
16. H. Zhu and G.-C. Fan, “Extracellular/circulating microRNAs and their potential role in cardiovascular disease,” American Journal of Cardiovascular Disease, vol. 1, no. 2, pp. 138–149, 2011.
17. S. Lee, E. Choi, M.-J. Cha, A.-J. Park, C. Yoon, and K.C. Hwang, “Impact of miRNAs on cardiovascular aging,” Journal of Geriatric Cardiology, vol. 12, no. 5, pp. 569–574, 2015.
18. C. de Lucia, K. Komici, G. Borghetti et al., “microRNA in cardiovascular aging and age-related cardiovascular diseases,” Frontiers in Medicine, vol. 4, p. 74, 2017.
19. WHO, “Global Health Observatory (GHO) data (World Health Organization),” 2016, http://www.who.int/gho/mortality_burden_disease/causes_death/top_10/en/.
20. R. A. Khalil, “Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease,” Biochemical Pharmacology, vol. 86, no. 12, pp. 1627–1642, 2013.
21. C. M. Klinge, “Estrogen receptor interaction with estrogen response elements,” Nucleic Acids Research, vol. 29, no. 14, pp. 2905–2919, 2001.
22. R. O’Lone, K. Knorr, I. Z. Jaffe et al., “Estrogen receptors α and β mediate distinct pathways of vascular gene expression, including genes involved in mitochondrial electron transport and generation of reactive oxygen species,” Molecular Endocrinology, vol. 21, no. 6, pp. 1281–1296, 2007.
23. M. K. Lindberg, S. Moverare, S. Skrtic et al., “Estrogen receptor (ER)-β reduces ERα-regulated gene transcription, supporting a “ying yang” relationship between ERα and ERβ in mice,” Molecular Endocrinology, vol. 17, no. 2, pp. 203–208, 2003.
24. S. Tsutsumi, X. Zhang, K. Takata et al., “Differential regulation of the inducible nitric oxide synthase gene by estrogen receptors 1 and 2,” The Journal of Endocrinology, vol. 199, no. 2, pp. 267–273, 2008.
25. T. Lahm, P. R. Crisostomo, T. A. Markel et al., “Selective estrogen receptor-α and estrogen receptor-β agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism,” American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 295, no. 5, pp. R1486–R1493, 2008.
26. P. A. Arias-Loza, K. Hu, C. Dienesch et al., “Both estrogen receptor subtypes, α and β, attenuate cardiovascular remodeling in aldosterone salt-treated rats,” Hypertension, vol. 50, no. 2, pp. 432–438, 2007.
27. E. Murphy and C. Steenbergen, “Estrogen regulation of protein expression and signaling pathways in the heart,” Biology of Sex Differences, vol. 5, no. 1, p. 6, 2014.
28. G. Pare, Á. Krust, R. H. Karas et al., “Estrogen receptor-α mediates the protective effects of estrogen against vascular injury,” Circulation Research, vol. 90, no. 10, pp. 1087–1092, 2002.
29. J.-F. Arnal, F. Lenfant, R. Metivier et al., “Membrane and nuclear estrogen receptor alpha actions: from tissue specificity to medical implications,” Physiological Reviews, vol. 97, no. 3, pp. 1045–1087, 2017.
30. C. M. Revankar, D. F. Cimino, L. A. Sklar, J. B. Arterburn, and E. R. Prossnitz, “A transmembrane intracellular estrogen receptor mediates rapid cell signaling,” Science, vol. 307, no. 5715, pp. 1625–1630, 2005.
31. T. Kondo, M. Hirose, and K. Kageyama, “Roles of oxidative stress and redox regulation in atherosclerosis,” Journal of Atherosclerosis and Thrombosis, vol. 16, no. 5, pp. 532–538, 2009.
32. M. Barton, “Cholesterol and atherosclerosis: modulation by oestrogen,” Current Opinion in Lipidology, vol. 24, no. 3, pp. 214–220, 2013.
33. V. Miller and S. Mulvagh, “Sex steroids and endothelial function: translating basic science to clinical practice,” Trends in Pharmacological Sciences, vol. 28, no. 6, pp. 263–270, 2007.
34. K. L. Chambliss and P. W. Shaul, “Estrogen modulation of endothelial nitric oxide synthase,” Endocrine Reviews, vol. 23, no. 5, pp. 665–686, 2002.
35. E. Monsalve, P. Oviedo, M. Garciaperez, J. Tarin, A. Cano, and C. Hermenegildo, “Estradiol counteracts oxidized LDL-induced asymmetric dimethylarginine production by cultured human endothelial cells,” Cardiovascular Research, vol. 73, no. 1, pp. 66–72, 2007.
36. S. Novella, A. Laguna-Fernández, M. Lázaro-Franco et al., “Estradiol, acting through estrogen receptor alpha, restores dimethylarginine dimethylaminohydrolase activity and nitric oxide production in oxLDL-treated human arterial endothelial cells,” Molecular and Cellular Endocrinology, vol. 365, no. 1, pp. 11–16, 2013.
37. A. Sobrino, P. J. Oviedo, S. Novella et al., “Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-α,” Journal of Molecular Endocrinology, vol. 44, no. 4, pp. 237–246, 2010.
38. R. K. Dubey, E. K. Jackson, P. J. Keller, B. Imthurn, and M. Rosselli, “Estradiol metabolites inhibit endothelin synthesis by an estrogen receptor-independent mechanism,” Hypertension, vol. 37, no. 2, pp. 640–644, 2001.
39. S. H. Juan, J. J. Chen, C. H. Chen et al., “17β-estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells,” American Journal of Physiology. Heart and Circulatory Physiology, vol. 287, no. 3, pp. H1254–H1261, 2004.
40. A. Suzuki, K. Mizuno, Y. Ino et al., “Effects of 17β-estradiol and progesterone on growth-factor-induced proliferation and migration in human female aortic smooth muscle cells in vitro,” Cardiovascular Research, vol. 32, no. 3, pp. 516–523, 1996.
41. A. Mügge, M. Riedel, M. Barton, M. Kuhn, and P. R. Lichtlen, “Endothelium independent relaxation of human coronary arteries by 17β-oestradiol in vitro,” Cardiovascular Research, vol. 27, no. 11, pp. 1939–1942, 1993.
42. 2+ entry mechanisms of coronary vasoconstriction,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 4, pp. 1034–1040, 1999.
43. + channels in human coronary artery smooth muscle cells,” Cardiovascular Research, vol. 53, no. 3, pp. 650–661, 2002.
44. J. Hiroki, H. Shimokawa, Y. Mukai, T. Ichiki, and A. Takeshita, “Divergent effects of estrogen and nicotine on Rho-kinase expression in human coronary vascular smooth muscle cells,” Biochemical and Biophysical Research Communications, vol. 326, no. 1, pp. 154–159, 2004.
45. C. A. Kanashiro and R. A. Khalil, “Gender-related distinctions in protein kinase C activity in rat vascular smooth muscle,” American Journal of Physiology. Cell Physiology, vol. 280, no. 1, pp. C34–C45, 2001.
46. K. Komukai, S. Mochizuki, and M. Yoshimura, “Gender and the renin–angiotensin–aldosterone system,” Fundamental & Clinical Pharmacology, vol. 24, no. 6, pp. 687–698, 2010.
47. A. Mompeón, M. Lázaro-Franco, C. Bueno-Betí et al., “Estradiol, acting through ERα, induces endothelial non-classic renin-angiotensin system increasing angiotensin 1–7 production,” Molecular and Cellular Endocrinology, vol. 422, pp. 1–8, 2016.
48. 1 receptor gene expression in vitro and in vivo,” Circulation, vol. 97, no. 22, pp. 2197–2201, 1998.
49. A. Sobrino, S. Vallejo, S. Novella et al., “Mas receptor is involved in the estrogen-receptor induced nitric oxide-dependent vasorelaxation,” Biochemical Pharmacology, vol. 129, pp. 67–72, 2017.
50. R. H. Straub, “The complex role of estrogens in inflammation,” Endocrine Reviews, vol. 28, no. 5, pp. 521–574, 2007.
51. Á. Álvarez, C. Hermenegildo, A. C. Issekutz, J. V. Esplugues, and M. J. Sanz, “Estrogens inhibit angiotensin II-induced leukocyte-endothelial cell interactions in vivo via rapid endothelial nitric oxide synthase and cyclooxygenase activation,” Circulation Research, vol. 91, no. 12, pp. 1142–1150, 2002.
52. M. Abu-Taha, C. Rius, C. Hermenegildo et al., “Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losartan,” Journal of Immunology, vol. 183, no. 2, pp. 1393–1402, 2009.
53. A. P. Miller, W. Feng, D. Xing et al., “Estrogen modulates inflammatory mediator expression and neutrophil chemotaxis in injured arteries,” Circulation, vol. 110, no. 12, pp. 1664–1669, 2004.
54. D. Xing, A. Miller, L. Novak, R. Rocha, Y. F. Chen, and S. Oparil, “Estradiol and progestins differentially modulate leukocyte infiltration after vascular injury,” Circulation, vol. 109, no. 2, pp. 234–241, 2004.
55. A. H. Wagner, M. R. Schroeter, and M. Hecker, “17β-estra-diol inhibition of NADPH oxidase expression in human endothelial cells,” The FASEB Journal, vol. 15, no. 12, pp. 2121–2130, 2001.
56. K. Strehlow, S. Rotter, S. Wassmann et al., “Modulation of antioxidant enzyme expression and function by estrogen,” Circulation Research, vol. 93, no. 2, pp. 170–177, 2003.
57. Z. Liu, Y. Gou, H. Zhang et al., “Estradiol improves cardiovascular function through up-regulation of SOD2 on vascular wall,” Redox Biology, vol. 3, pp. 88–99, 2014.
58. J. A. McCrohon, S. Nakhla, W. Jessup, K. K. Stanley, and D. S. Celermajer, “Estrogen and progesterone reduce lipid accumulation in human monocyte-derived macrophages: a sex-specific effect,” Circulation, vol. 100, no. 23, pp. 2319–2325, 1999.
59. H. Wang, Y. Liu, L. Zhu et al., “17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway,” International Journal of Molecular Medicine, vol. 33, no. 3, pp. 550–558, 2014.
60. B. A. Walsh, A. E. Mullick, R. L. Walzem, and J. C. Rutledge, “17β-estradiol reduces tumor necrosis factor-α-mediated LDL accumulation in the artery wall,” Journal of Lipid Research, vol. 40, no. 3, pp. 387–396, 1999.
61. N. Townsend, L. Wilson, P. Bhatnagar, K. Wickramasinghe, M. Rayner, and M. Nichols, “Cardiovascular disease in Europe: epidemiological update 2016,” European Heart Journal, vol. 37, no. 42, pp. 3232–3245, 2016.
62. A. A. Merz and S. Cheng, “Sex differences in cardiovascular ageing,” Heart, vol. 102, no. 11, pp. 825–831, 2016.
63. R. A. Lobo, “Hormone-replacement therapy: current thinking,” Nature Reviews. Endocrinology, vol. 13, no. 4, pp. 220–231, 2017.
64. J. D. Erusalimsky, “Vascular endothelial senescence: from mechanisms to pathophysiology,” Journal of Applied Physiology, vol. 106, no. 1, pp. 326–332, 2009.
65. J. O. Fajemiroye, L. C. Cunha, R. Saavedra-Rodríguez et al., “Aging-induced biological changes and cardiovascular diseases,” BioMed Research International, vol. 2018, Article ID 7156435, 14 pages, 2018.
66. K. L. Moreau and K. L. Hildreth, “Vascular aging across the menopause transition in healthy women,” Advances in Vascular Medicine, vol. 2014, Article ID 204390, 12 pages, 2014.
67. C. J. Nicholson, M. Sweeney, S. C. Robson, and M. J. Taggart, “Estrogenic vascular effects are diminished by chronological aging,” Scientific Reports, vol. 7, no. 1, article 12153, 2017.
68. M. D. Herrera, C. Mingorance, R. Rodríguez-Rodríguez, and M. Alvarez de Sotomayor, “Endothelial dysfunction and aging: an update,” Ageing Research Reviews, vol. 9, no. 2, pp. 142–152, 2010.
69. L. Rodríguez-Mañas, M. el-Assar, S. Vallejo et al., “Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation,” Aging Cell, vol. 8, no. 3, pp. 226–238, 2009.
70. S. Novella, A. P. Dantas, G. Segarra et al., “Gathering of aging and estrogen withdrawal in vascular dysfunction of senescent accelerated mice,” Experimental Gerontology, vol. 45, no. 11, pp. 868–874, 2010.
71. S. Novella, A. P. Dantas, G. Segarra et al., “Aging-related endothelial dysfunction in the aorta from female senescence-accelerated mice is associated with decreased nitric oxide synthase expression,” Experimental Gerontology, vol. 48, no. 11, pp. 1329–1337, 2013.
72. S. B. A. Cau, F. S. Carneiro, and R. C. Tostes, “Differential modulation of nitric oxide synthases in aging: therapeutic opportunities,” Frontiers in Physiology, vol. 3, p. 218, 2012.
73. Y.-I. Yoshida, S. Eda, and M. Masada, “Alterations of tetrahydrobiopterin biosynthesis and pteridine levels in mouse tissues during growth and aging,” Brain and Development, vol. 22, pp. 45–49, 2000.
74. Y. Xiong, L. W. Yuan, H. W. Deng, Y. J. Li, and B. M. Chen, “Elevated serum endogenous inhibitor of nitric oxide synthase and endothelial dysfunction in aged rats,” Clinical and Experimental Pharmacology & Physiology, vol. 28, no. 10, pp. 842–847, 2001.
75. 2 in aorta from female senescence-accelerated mice,” Age, vol. 35, no. 1, pp. 117–128, 2013.
76. V. B. O’Donnell and B. A. Freeman, “Interactions between nitric oxide and lipid oxidation pathways,” Circulation Research, vol. 88, no. 1, pp. 12–21, 2001.
77. M. El Assar, J. Angulo, and L. Rodríguez-Mañas, “Oxidative stress and vascular inflammation in aging,” Free Radical Biology & Medicine, vol. 65, pp. 380–401, 2013.
78. L. S. Kang, B. Chen, R. A. Reyes et al., “Aging and estrogen alter endothelial reactivity to reactive oxygen species in coronary arterioles,” American Journal of Physiology. Heart and Circulatory Physiology, vol. 300, no. 6, pp. H2105–H2115, 2011.
79. X. Vidal-Gomez, S. Novella, I. Perez-Monzo et al., “Decreased bioavailability of nitric oxide in aorta from ovariectomized senescent mice. Role of cyclooxygenase,” Experimental Gerontology, vol. 76, pp. 1–8, 2016.
80. B. A. Monk and S. J. George, “The effect of ageing on vascular smooth muscle cell behaviour - a mini-review,” Gerontology, vol. 61, no. 5, pp. 416–426, 2015.
81. B. P. McGrath, Y.-L. Liang, H. Teede, L. M. Shiel, J. D. Cameron, and A. Dart, “Age-related deterioration in arterial structure and function in postmenopausal women,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 7, pp. 1149–1156, 1998.
82. Y. Zhang, K. G. Stewart, and S. T. Davidge, “Estrogen replacement reduces age-associated remodeling in rat mesenteric arteries,” Hypertension, vol. 36, no. 6, pp. 970–974, 2000.
83. K. C. Lewandowski, J. Komorowski, D. P. Mikhalidis et al., “Effects of hormone replacement therapy type and route of administration on plasma matrix metalloproteinases and their tissue inhibitors in postmenopausal women,” The Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 8, pp. 3123–3130, 2006.
84. P. Lacolley, V. Regnault, and A. P. Avolio, “Smooth muscle cell and arterial aging: basic and clinical aspects,” Cardiovascular Research, vol. 114, no. 4, pp. 513–528, 2018.
85. H. Qiu, B. Tian, R. G. Resuello et al., “Sex-specific regulation of gene expression in the aging monkey aorta,” Physiological Genomics, vol. 29, no. 2, pp. 169–180, 2007.
86. T. Mori, J. Durand, Y.-F. Chen, J. A. Thompson, S. Bakir, and S. Oparil, “Effects of short-term estrogen treatment on the neointimal response to balloon injury of rat carotid artery,” The American Journal of Cardiology, vol. 85, no. 10, pp. 1276–1279, 2000.
87. C. Franceschi, P. Garagnani, G. Vitale, M. Capri, and S. Salvioli, “Inflammaging and ‘Garb-aging’,” Trends in Endocrinology & Metabolism, vol. 28, no. 3, pp. 199–212, 2017.
88. A. Csiszar, M. Wang, E. G. Lakatta, and Z. Ungvari, “Inflammation and endothelial dysfunction during aging: role of NF-κB,” Journal of Applied Physiology, vol. 105, no. 4, pp. 1333–1341, 2008.
89. S. Novella, M. Heras, C. Hermenegildo, and A. P. Dantas, “Effects of estrogen on vascular inflammation: a matter of timing,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 8, pp. 2035–2042, 2012.
90. M. R. Bowling, D. Xing, A. Kapadia et al., “Estrogen effects on vascular inflammation are age dependent: role of estrogen receptors,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 34, no. 7, pp. 1477–1485, 2014.
91. L. Novensà, S. Novella, P. Medina et al., “Aging negatively affects estrogens-mediated effects on nitric oxide bioavailability by shifting ERα/ERβ balance in female mice,” PLoS One, vol. 6, no. 9, article e25335, 2011.
92. Y. S. Rao, N. N. Mott, Y. Wang, W. C. J. Chung, and T. R. Pak, “MicroRNAs in the aging female brain: a putative mechanism for age-specific estrogen effects,” Endocrinology, vol. 154, no. 8, pp. 2795–2806, 2013.
93. D. Guo, Y. Ye, J. Qi et al., “Age and sex differences in microRNAs expression during the process of thymus aging,” Acta Biochimica et Biophysica Sinica, vol. 49, no. 5, pp. 409–419, 2017.
94. J. C. Kwekel, V. Vijay, V. G. Desai, C. L. Moland, and J. C. Fuscoe, “Age and sex differences in kidney microRNA expression during the life span of F344 rats,” Biology of Sex Differences, vol. 6, no. 1, p. 1, 2015.
95. G. Cizeron-Clairac, F. Lallemand, S. Vacher, R. Lidereau, I. Bieche, and C. Callens, “MiR-190b, the highest upregulated miRNA in ERα-positive compared to ERα-negative breast tumors, a new biomarker in breast cancers?,” BMC Cancer, vol. 15, no. 1, p. 499, 2015.
96. S. T. Bailey, T. Westerling, and M. Brown, “Loss of estrogen-regulated microRNA expression increases HER2 signaling and is prognostic of poor outcome in luminal breast cancer,” Cancer Research, vol. 75, no. 2, pp. 436–445, 2015.
97. J. Zhao, G. A. Imbrie, W. E. Baur et al., “Estrogen receptor-mediated regulation of microRNA inhibits proliferation of vascular smooth muscle cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 2, pp. 257–265, 2013.
98. X. Vidal-Gómez, D. Pérez-Cremades, A. Mompeón, A. P. Dantas, S. Novella, and C. Hermenegildo, “microRNA as crucial regulators of gene expression in estradiol-treated human endothelial cells,” Cellular Physiology and Biochemistry, vol. 45, no. 5, pp. 1878–1892, 2018.
99. R. Song, S. Ro, J. D. Michaels, C. Park, J. R. McCarrey, and W. Yan, “Many X-linked microRNAs escape meiotic sex chromosome inactivation,” Nature Genetics, vol. 41, no. 4, pp. 488–493, 2009.
100. B. R. Migeon, “The role of x inactivation and cellular mosaicism in women’s health and sex-specific diseases,” JAMA, vol. 295, no. 12, pp. 1428–1433, 2006.
101. B. W. Florijn, R. Bijkerk, E. P. van der Veer, and A. J. van Zonneveld, “Gender and cardiovascular disease: are sex-biased microRNA networks a driving force behind heart failure with preserved ejection fraction in women?,” Cardiovascular Research, vol. 114, no. 2, pp. 210–225, 2018.
102. V. N. Kim, J. Han, and M. C. Siomi, “Biogenesis of small RNAs in animals,” Nature Reviews. Molecular Cell Biology, vol. 10, no. 2, pp. 126–139, 2009.
103. C. Borrás, E. Serna, J. Gambini, M. Inglés, and J. Vina, “Centenarians maintain miRNA biogenesis pathway while it is impaired in octogenarians,” Mechanisms of Ageing and Development, vol. 168, pp. 54–57, 2017.
104. Z. Ungvari, Z. Tucsek, D. Sosnowska et al., “Aging-induced dysregulation of Dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells,” The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. 68, no. 8, pp. 877–891, 2013.
105. W. J. Yang, D. D. Yang, S. Na, G. E. Sandusky, Q. Zhang, and G. Zhao, “Dicer is required for embryonic angiogenesis during mouse development,” The Journal of Biological Chemistry, vol. 280, no. 10, pp. 9330–9335, 2005.
106. Y. Suarez, C. Fernandez-Hernando, J. S. Pober, and W. C. Sessa, “Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells,” Circulation Research, vol. 100, no. 8, pp. 1164–1173, 2007.
107. A. Kuehbacher, C. Urbich, A. M. Zeiher, and S. Dimmeler, “Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis,” Circulation Research, vol. 101, no. 1, pp. 59–68, 2007.
108. A. Gupta, E. Caffrey, G. Callagy, and S. Gupta, “Oestrogen-dependent regulation of miRNA biogenesis: many ways to skin the cat,” Biochemical Society Transactions, vol. 40, no. 4, pp. 752–758, 2012.
109. C. Cheng, X. Fu, P. Alves, and M. Gerstein, “mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer,” Genome Biology, vol. 10, no. 9, p. R90, 2009.
110. P. Bhat-Nakshatri, G. Wang, N. R. Collins et al., “Estradiol-regulated microRNAs control estradiol response in breast cancer cells,” Nucleic Acids Research, vol. 37, no. 14, pp. 4850–4861, 2009.
111. O. Paris, L. Ferraro, O. M. V. Grober et al., “Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer,” Oncogene, vol. 31, no. 38, pp. 4196–4206, 2012.
112. W. B. Nothnick, C. Healy, and X. Hong, “Steroidal regulation of uterine miRNAs is associated with modulation of the miRNA biogenesis components Exportin-5 and Dicer1,” Endocrine, vol. 37, no. 2, pp. 265–273, 2010.
113. D. Pérez-Cremades, A. Mompeón, X. Vidal-Gómez, C. Hermenegildo, and S. Novella, “miRNA as a new regulatory mechanism of estrogen vascular action,” International Journal of Biological Sciences, vol. 19, no. 2, p. 473, 2018.
114. J. H. An, J. H. Ohn, J. A. Song et al., “Changes of microRNA profile and microRNA-mRNA regulatory network in bones of ovariectomized mice,” Journal of Bone and Mineral Research, vol. 29, no. 3, pp. 644–656, 2014.
115. J. Chen, K. Li, Q. Pang et al., “Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis,” Scientific Reports, vol. 6, no. 1, article 36347, 2016.
116. F. Olivieri, M. Ahtiainen, R. Lazzarini et al., “Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-223 expressions: a study on postmenopausal monozygotic twin pairs,” Aging Cell, vol. 13, no. 5, pp. 850–861, 2014.
117. R. Kangas, C. Morsiani, G. Pizza et al., “Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement,” Oncotarget, vol. 9, no. 2, pp. 2279–2294, 2018.
118. P. Vrtacnik, B. Ostanek, S. Mencej-Bedrac, and J. Marc, “The many faces of estrogen signaling,” Biochemical Medicine, vol. 24, no. 3, pp. 329–342, 2014.
119. Y.-M. Park, C. Erickson, D. Bessesen, R. E. Van Pelt, and K. Cox-York, “Age- and menopause-related differences in subcutaneous adipose tissue estrogen receptor mRNA expression,” Steroids, vol. 121, pp. 17–21, 2017.
120. H. Yamatani, K. Takahashi, T. Yoshida, T. Soga, and H. Kurachi, “Differences in the fatty acid metabolism of visceral adipose tissue in postmenopausal women,” Menopause, vol. 21, no. 2, pp. 170–176, 2014.
121. R. Kangas, E. Pollanen, M. R. Rippo et al., “Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy–a study with monozygotic twin pairs,” Mechanisms of Ageing and Development, vol. 143-144, pp. 1–8, 2014.
122. R. Kangas, T. Tormakangas, V. Fey et al., “Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy,” Scientific Reports, vol. 7, no. 1, article 42702, 2017.
123. J. E. Fish, M. M. Santoro, S. U. Morton et al., “miR-126 regulates angiogenic signaling and vascular integrity,” Developmental Cell, vol. 15, no. 2, pp. 272–284, 2008.
124. S. Wang, A. B. Aurora, B. A. Johnson et al., “The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis,” Developmental Cell, vol. 15, no. 2, pp. 261–271, 2008.
125. T. A. Harris, M. Yamakuchi, M. Ferlito, J. T. Mendell, and C. J. Lowenstein, “MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 5, pp. 1516–1521, 2008.
126. J. Zhou, Y. S. Li, P. Nguyen et al., “Regulation of vascular smooth muscle cell turnover by endothelial cell-secreted microRNA-126: role of shear stress,” Circulation Research, vol. 113, no. 1, pp. 40–51, 2013.
127. P. Li, J. Wei, X. Li et al., “17β-estradiol enhances vascular endothelial Ets-1/miR-126-3p expression: the possible mechanism for attenuation of atherosclerosis,” The Journal of Clinical Endocrinology and Metabolism, vol. 102, no. 2, pp. 594–603, 2017.
128. R. Dai, R. A. Phillips, Y. Zhang, D. Khan, O. Crasta, and S. A. Ahmed, “Suppression of LPS-induced interferon-γ and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation,” Blood, vol. 112, no. 12, pp. 4591–4597, 2008.
129. F. Jansen, T. Stumpf, S. Proebsting et al., “Intercellular transfer of miR-126-3p by endothelial microparticles reduces vascular smooth muscle cell proliferation and limits neointima formation by inhibiting LRP6,” Journal of Molecular and Cellular Cardiology, vol. 104, pp. 43–52, 2017.
130. D. A. Chistiakov, A. N. Orekhov, and Y. V. Bobryshev, “The role of miR-126 in embryonic angiogenesis, adult vascular homeostasis, and vascular repair and its alterations in atherosclerotic disease,” Journal of Molecular and Cellular Cardiology, vol. 97, pp. 47–55, 2016.
131. Y. Fukushima, M. Nakanishi, H. Nonogi, Y. Goto, and N. Iwai, “Assessment of plasma miRNAs in congestive heart failure,” Circulation Journal, vol. 75, no. 2, pp. 336–340, 2011.
132. H. Li, X. Zhao, Y. Z. Liu et al., “Plasma microRNA-126-5p is associated with the complexity and severity of coronary artery disease in patients with stable angina pectoris,” Cellular Physiology and Biochemistry, vol. 39, no. 3, pp. 837–846, 2016.
133. A. ElSharawy, A. Keller, F. Flachsbart et al., “Genome-wide miRNA signatures of human longevity,” Aging Cell, vol. 11, no. 4, pp. 607–616, 2012.
134. F. Olivieri, M. Bonafè, L. Spazzafumo et al., “Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells,” Aging, vol. 6, no. 9, pp. 771–786, 2014.
135. A. M. Queirós, C. Eschen, D. Fliegner et al., “Sex- and estrogen-dependent regulation of a miRNA network in the healthy and hypertrophied heart,” International Journal of Cardiology, vol. 169, no. 5, pp. 331–338, 2013.
136. M. Hackl, S. Brunner, K. Fortschegger et al., “miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging,” Aging Cell, vol. 9, no. 2, pp. 291–296, 2010.
137. H. Zhang, H. Yang, C. Zhang et al., “Investigation of microRNA expression in human serum during the aging process,” The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. 70, no. 1, pp. 102–109, 2015.
138. J. Zhang, S.-F. Li, H. Chen, and J.-X. Song, “MiR-106b-5p inhibits tumor necrosis factor-α-induced apoptosis by targeting phosphatase and tensin homolog deleted on chromosome 10 in vascular endothelial cells,” Chinese Medical Journal, vol. 129, no. 12, pp. 1406–1412, 2016.
139. Z. Liu, D. Yang, P. Xie et al., “MiR-106b and MiR-15b modulate apoptosis and angiogenesis in myocardial infarction,” Cellular Physiology and Biochemistry, vol. 29, no. 5-6, pp. 851–862, 2012.
140. E. M. Noh, Y. R. Lee, K. O. Chay et al., “Estrogen receptor α induces down-regulation of PTEN through PI3-kinase activation in breast cancer cells,” Molecular Medicine Reports, vol. 4, no. 2, pp. 215–219, 2011.
141. J. A. Smith, R. Zhang, A. K. Varma, A. Das, S. K. Ray, and N. L. Banik, “Estrogen partially down-regulates PTEN to prevent apoptosis in VSC4.1 motoneurons following exposure to IFN-γ,” Brain Research, vol. 1301, pp. 163–170, 2009.
142. C. Rippe, M. Blimline, K. A. Magerko et al., “MicroRNA changes in human arterial endothelial cells with senescence: relation to apoptosis, eNOS and inflammation,” Experimental Gerontology, vol. 47, no. 1, pp. 45–51, 2012.
143. A. M. Evangelista, A. M. Deschamps, D. Liu, N. Raghavachari, and E. Murphy, “miR-222 contributes to sex-dimorphic cardiac eNOS expression via ets-1,” Physiological Genomics, vol. 45, no. 12, pp. 493–498, 2013.
144. B. Ostadal and P. Ostadal, “Sex-based differences in cardiac ischaemic injury and protection: therapeutic implications,” British Journal of Pharmacology, vol. 171, no. 3, pp. 541–554, 2014.
145. G. Di Leva, P. Gasparini, C. Piovan et al., “MicroRNA cluster 221-222 and estrogen receptor α interactions in breast cancer,” Journal of the National Cancer Institute, vol. 102, no. 10, pp. 706–721, 2010.
146. X. Liu, Y. Cheng, S. Zhang, Y. Lin, J. Yang, and C. Zhang, “A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia,” Circulation Research, vol. 104, no. 4, pp. 476–487, 2009.
147. K. R. Cordes, N. T. Sheehy, M. P. White et al., “miR-145 and miR-143 regulate smooth muscle cell fate decisions,” Nature, vol. 460, pp. 705–710, 2009.
148. T. Boettger, N. Beetz, S. Kostin et al., “Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster,” The Journal of Clinical Investigation, vol. 119, no. 9, pp. 2634–2647, 2009.
149. E. Hergenreider, S. Heydt, K. Tréguer et al., “Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs,” Nature Cell Biology, vol. 14, no. 3, pp. 249–256, 2012.
150. L. Deng, F. J. Blanco, H. Stevens et al., “MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension,” Circulation Research, vol. 117, no. 10, pp. 870–883, 2015.
151. J. Faccini, J.-B. Ruidavets, P. Cordelier et al., “Circulating miR-155, miR-145 and let-7c as diagnostic biomarkers of the coronary artery disease,” Scientific Reports, vol. 7, no. 1, article 42916, 2017.
152. S. Kuokkanen, B. Chen, L. Ojalvo, L. Benard, N. Santoro, and J. W. Pollard, “Genomic profiling of microRNAs and messenger RNAs reveals hormonal regulation in microRNA expression in human endometrium,” Biology of Reproduction, vol. 82, no. 4, pp. 791–801, 2010.
153. N. Mellios, M. Galdzicka, E. Ginns et al., “Gender-specific reduction of estrogen-sensitive small RNA, miR-30b, in subjects with schizophrenia,” Schizophrenia Bulletin, vol. 38, no. 3, pp. 433–443, 2012.
154. 2+ /calmodulin-dependent protein kinase IIδ (CaMKIIδ),” Scientific Reports, vol. 6, no. 1, article 26166, 2016.
155. Y. Huang, J. Chen, Y. Zhou et al., “Circulating miR-30 is related to carotid artery atherosclerosis,” Clinical and Experimental Hypertension, vol. 38, no. 5, pp. 489–494, 2016.
156. C. Jentzsch, S. Leierseder, X. Loyer et al., “A phenotypic screen to identify hypertrophy-modulating microRNAs in primary cardiomyocytes,” Journal of Molecular and Cellular Cardiology, vol. 52, no. 1, pp. 13–20, 2012.
157. W. Pan, Y. Zhong, C. Cheng et al., “MiR-30-regulated autophagy mediates angiotensin II-induced myocardial hypertrophy,” PLoS One, vol. 8, no. 1, article e53950, 2013.
158. Y. Shen, Z. Shen, L. Miao et al., “miRNA-30 family inhibition protects against cardiac ischemic injury by regulating cystathionine-γ-lyase expression,” Antioxidants & Redox Signaling, vol. 22, no. 3, pp. 224–240, 2015.
159. G. Bridge, R. Monteiro, S. Henderson et al., “The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis,” Blood, vol. 120, no. 25, pp. 5063–5072, 2012.
160. S. Demolli, C. Doebele, A. Doddaballapur et al., “MicroRNA-30 mediates anti-inflammatory effects of shear stress and KLF2 via repression of angiopoietin 2,” Journal of Molecular and Cellular Cardiology, vol. 88, pp. 111–119, 2015.
161. F. Li, Q. Chen, X. Song, L. Zhou, and J. Zhang, “MiR-30b is involved in the homocysteine-induced apoptosis in human coronary artery endothelial cells by regulating the expression of caspase 3,” International Journal of Molecular Sciences, vol. 16, no. 8, pp. 17682–17695, 2015.
162. D. Xing, S. Nozell, Y.-F. Chen, F. Hage, and S. Oparil, “Estrogen and mechanisms of vascular protection,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 3, pp. 289–295, 2009.
163. C. Bang, J. A. N. Fiedler, and T. Thum, “Cardiovascular importance of the microRNA-23/27/24 family,” Microcirculation, vol. 19, no. 3, pp. 208–214, 2012.
164. H. Dellago, B. Preschitz-Kammerhofer, L. Terlecki-Zaniewicz et al., “High levels of oncomiR-21 contribute to the senescence-induced growth arrest in normal human cells and its knock-down increases the replicative lifespan,” Aging Cell, vol. 12, no. 3, pp. 446–458, 2013.
165. Z. Luo, X. Feng, H. Wang et al., “Mir-23a induces telomere dysfunction and cellular senescence by inhibiting TRF2 expression,” Aging Cell, vol. 14, no. 3, pp. 391–399, 2015.
166. N. Wang, L.-Y. Sun, S.-C. Zhang et al., “MicroRNA-23a participates in estrogen deficiency induced gap junction remodeling of rats by targeting GJA1,” International Journal of Biological Sciences, vol. 11, no. 4, pp. 390–403, 2015.
167. B. M. P. Gowd and P. D. Thompson, “Effect of female sex on cardiac arrhythmias,” Cardiology in Review, vol. 20, no. 6, pp. 297–303, 2012.
168. K. Wang, Z.-Q. Lin, B. Long, J.-H. Li, J. Zhou, and P.-F. Li, “Cardiac hypertrophy is positively regulated by microRNA miR-23a,” The Journal of Biological Chemistry, vol. 287, no. 1, pp. 589–599, 2011.
169. L.-Y. Sun, N. Wang, T. Ban et al., “MicroRNA-23a mediates mitochondrial compromise in estrogen deficiency-induced concentric remodeling via targeting PGC-1α,” Journal of Molecular and Cellular Cardiology, vol. 75, pp. 1–11, 2014.
170. L. Goedeke, N. Rotllan, C. M. Ramírez et al., “miR-27b inhibits LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels in mice,” Atherosclerosis, vol. 243, no. 2, pp. 499–509, 2015.
171. S. Dolz, D. Górriz, J. I. Tembl et al., “Circulating microRNAs as novel biomarkers of stenosis progression in asymptomatic carotid stenosis,” Stroke, vol. 48, no. 1, pp. 10–16, 2017.
172. J. Lin, L. Wang, J. Gao, and S. Zhu, “MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells,” Experimental and Therapeutic Medicine, vol. 14, no. 3, pp. 2702–2708, 2017.
173. C. J. Nicholson, F. Seta, S. Lee, and K. G. Morgan, “MicroRNA-203 mimics age-related aortic smooth muscle dysfunction of cytoskeletal pathways,” Journal of Cellular and Molecular Medicine, vol. 21, no. 1, pp. 81–95, 2017.
174. H. Li, J. Zhou, X. Wei et al., “miR-144 and targets, c-fos and cyclooxygenase-2 (COX2), modulate synthesis of PGE2 in the amnion during pregnancy and labor,” Scientific Reports, vol. 6, no. 1, article 27914, 2016.
175. X. Wang, H. Zhu, X. Zhang et al., “Loss of the miR-144/451 cluster impairs ischaemic preconditioning-mediated cardioprotection by targeting Rac-1,” Cardiovascular Research, vol. 94, no. 2, pp. 379–390, 2012.
176. A. Csiszar, T. Gautam, D. Sosnowska et al., “Caloric restriction confers persistent anti-oxidative, pro-angiogenic, and anti-inflammatory effects and promotes anti-aging miRNA expression profile in cerebromicrovascular endothelial cells of aged rats,” American Journal of Physiology. Heart and Circulatory Physiology, vol. 307, no. 3, pp. H292–H306, 2014.
177. C. M. Ramírez, N. Rotllan, A. V. Vlassov et al., “Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144,” Circulation Research, vol. 112, no. 12, pp. 1592–1601, 2013.
178. M. P. Corcoran, A. H. Lichtenstein, M. Meydani, A. Dillard, E. J. Schaefer, and S. Lamon-Fava, “The effect of 17β-estradiol on cholesterol content in human macrophages is influenced by the lipoprotein milieu,” Journal of Molecular Endocrinology, vol. 47, no. 1, pp. 109–117, 2011.
179. H. S. Cheng, N. Sivachandran, A. Lau et al., “MicroRNA-146 represses endothelial activation by inhibiting proinflammatory pathways,” EMBO Molecular Medicine, vol. 5, no. 7, pp. 1017–1034, 2013.
180. F. Olivieri, R. Lazzarini, R. Recchioni et al., “MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling,” Age, vol. 35, no. 4, pp. 1157–1172, 2013.
181. M. Vasa-Nicotera, H. Chen, P. Tucci et al., “miR-146a is modulated in human endothelial cell with aging,” Atherosclerosis, vol. 217, no. 2, pp. 326–330, 2011.
182. X. Zhang, G. Azhar, and J. Y. Wei, “The expression of microRNA and microRNA clusters in the aging heart,” PLoS One, vol. 7, no. 4, article e34688, 2012.
183. F. Olivieri, L. Spazzafumo, G. Santini et al., “Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging,” Mechanisms of Ageing and Development, vol. 133, no. 11-12, pp. 675–685, 2012.
184. Y. Zhang, Y. J. Liu, T. Liu, H. Zhang, and S. J. Yang, “Plasma microRNA-21 is a potential diagnostic biomarker of acute myocardial infarction,” European Review for Medical and Pharmacological Sciences, vol. 20, no. 2, pp. 323–329, 2016.
185. T. Thum, C. Gross, J. Fiedler et al., “MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts,” Nature, vol. 456, no. 7224, pp. 980–984, 2008.
186. J. Zhou, K. C. Wang, W. Wu et al., “MicroRNA-21 targets peroxisome proliferators-activated receptor-α in an autoregulatory loop to modulate flow-induced endothelial inflammation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 25, pp. 10355–10360, 2011.
187. R. Ji, Y. Cheng, J. Yue et al., “MicroRNA expression signature and antisense-mediated depletion reveal an essential role of microRNA in vascular neointimal lesion formation,” Circulation Research, vol. 100, no. 11, pp. 1579–1588, 2007.
188. N. S. Wickramasinghe, T. T. Manavalan, S. M. Dougherty, K. A. Riggs, Y. Li, and C. M. Klinge, “Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells,” Nucleic Acids Research, vol. 37, no. 8, pp. 2584–2595, 2009.
189. A. Luchner, U. Bröckel, M. Muscholl et al., “Gender-specific differences of cardiac remodeling in subjects with left ventricular dysfunction: a population-based study,” Cardiovascular Research, vol. 53, no. 3, pp. 720–727, 2002.
190. R. A. Boon, K. Iekushi, S. Lechner et al., “MicroRNA-34a regulates cardiac ageing and function,” Nature, vol. 495, no. 7439, pp. 107–110, 2013.
191. T. Ito, S. Yagi, and M. Yamakuchi, “MicroRNA-34a regulation of endothelial senescence,” Biochemical and Biophysical Research Communications, vol. 398, no. 4, pp. 735–740, 2010.
192. I. Badi, I. Burba, C. Ruggeri et al., “MicroRNA-34a induces vascular smooth muscle cells senescence by SIRT1 downregulation and promotes the expression of age-associated proinflammatory secretory factors,” The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. 70, no. 11, pp. 1304–1311, 2015.
193. B. C. Bernardo, X. M. Gao, C. E. Winbanks et al., “Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 43, pp. 17615–17620, 2012.
194. S. Nanni, A. Aiello, A. Re et al., “Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer,” PLoS One, vol. 8, no. 5, article e62522, 2013.
195. B. C. Bernardo, J. Y. Y. Ooi, A. Matsumoto et al., “Sex differences in response to miRNA-34a therapy in mouse models of cardiac disease: identification of sex-, disease- and treatment-regulated miRNAs,” The Journal of Physiology, vol. 594, no. 20, pp. 5959–5974, 2016.
196. V. Jazbutyte, J. Fiedler, S. Kneitz et al., “MicroRNA-22 increases senescence and activates cardiac fibroblasts in the aging heart,” Age, vol. 35, no. 3, pp. 747–762, 2013.
197. S. K. Gupta, A. Foinquinos, S. Thum et al., “Preclinical development of a microRNA-based therapy for elderly patients with myocardial infarction,” Journal of the American College of Cardiology, vol. 68, no. 14, pp. 1557–1571, 2016.
198. L. Wang, Z. P. Tang, W. Zhao et al., “MiR-22/Sp-1 links estrogens with the up-regulation of cystathionine γ-lyase in myocardium, which contributes to estrogenic cardioprotection against oxidative stress,” Endocrinology, vol. 156, no. 6, pp. 2124–2137, 2015.
199. J. Schweisgut, C. Schutt, S. Wust et al., “Sex-specific, reciprocal regulation of ERα and miR-22 controls muscle lipid metabolism in male mice,” The EMBO Journal, vol. 36, no. 9, pp. 1199–1214, 2017.
200. S. Banerjee, H. Cui, N. Xie et al., “miR-125a-5p regulates differential activation of macrophages and inflammation,” The Journal of Biological Chemistry, vol. 288, no. 49, pp. 35428–35436, 2013.
201. A. J. Murphy, P. M. Guyre, and P. A. Pioli, “Estradiol suppresses NF-κB activation through coordinated regulation of let-7a and miR-125b in primary human macrophages,” Journal of Immunology, vol. 184, no. 9, pp. 5029–5037, 2010.
202. P. Che, J. Liu, Z. Shan et al., “miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1 downregulation,” Aging Cell, vol. 13, no. 5, pp. 926–934, 2014.