Endothelial cell metabolism: A novel player in atherosclerosis? Basic principles and therapeutic opportunities

Atherosclerosis

Volumn 253, Issue , 2016, Pages 247-257

  Pircher, Andreas ^a,b   Treps, Lucas ^a,b   Bodrug, Natalia ^a,b,c   Carmeliet, Peter ^a,b  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Angiogenesis; Atherosclerosis; Endothelial cell; Endothelial cell metabolism; Glycolysis

Indexed keywords

AMINO ACID; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FATTY ACID; LIPOPROTEIN; MEVALONIC ACID; REACTIVE OXYGEN METABOLITE; SPHINGOLIPID; UBIDECARENONE;

AMINO ACID METABOLISM; ANGIOGENESIS; ATHEROSCLEROSIS; BLOOD FLOW; CELL METABOLISM; DISEASE COURSE; ENDOTHELIUM CELL; FATTY ACID METABOLISM; GLYCOLYSIS; HUMAN; INTESTINE FLORA; NONHUMAN; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; REVIEW; ANIMAL; BLOOD FLOW VELOCITY; METABOLISM; MOUSE; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY;

AMINO ACIDS; ANIMALS; ATHEROSCLEROSIS; BLOOD FLOW VELOCITY; ENDOTHELIAL CELLS; FATTY ACIDS; GASTROINTESTINAL MICROBIOME; GLYCOLYSIS; HUMANS; MICE; NEOVASCULARIZATION, PATHOLOGIC;

EID: 84992070913     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2016.08.011     Document Type: Review

References (152)

1. [1] Mozaffarian, D., Benjamin, E.J., Go, A.S., et al. Heart disease and stroke statistics-2016 update: a report from the american heart association. Circulation 133 (2016), e38–e360.
2. [2] Gimbrone, M.A. Jr., Garcia-Cardena, G., Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ. Res. 118 (2016), 620–636.
3. [3] Libby, P., Bornfeldt, K.E., Tall, A.R., Atherosclerosis: successes, surprises, and future challenges. Circ. Res. 118 (2016), 531–534.
4. [4] De Bock, K., Georgiadou, M., Carmeliet, P., Role of endothelial cell metabolism in vessel sprouting. Cell metab. 18 (2013), 634–647.
5. [5] Buchwald, P., A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets. Theor. Biol. Med. Model, 8, 2011, 20.
6. [6] Locasale, J.W., Cantley, L.C., Metabolic flux and the regulation of mammalian cell growth. Cell metab. 14 (2011), 443–451.
7. [7] Vander Heiden, M.G., Cantley, L.C., Thompson, C.B., Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324 (2009), 1029–1033.
8. [8] Krutzfeldt, A., Spahr, R., Mertens, S., et al. Metabolism of exogenous substrates by coronary endothelial cells in culture. J. Mol. Cell Cardiol. 22 (1990), 1393–1404.
9. [9] De Bock, K., Georgiadou, M., Schoors, S., et al. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154 (2013), 651–663.
10. [10] Schoors, S., De Bock, K., Cantelmo, A.R., et al. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis. Cell metab. 19 (2014), 37–48.
11. [11] Peters, K., Kamp, G., Berz, A., et al. Changes in human endothelial cell energy metabolic capacities during in vitro cultivation. The role of “aerobic glycolysis” and proliferation. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol., Biochem. Pharmacol. 24 (2009), 483–492.
12. [12] Dobrina, A., Rossi, F., Metabolic properties of freshly isolated bovine endothelial cells. Biochim. Biophys. Acta 762 (1983), 295–301.
13. [13] Love, D.C., Hanover, J.A., The hexosamine signaling pathway: deciphering the “O-GlcNAc code”. Sci. STKE, re13, 2005.
14. [14] Koo, A., Dewey, C.F. Jr., Garcia-Cardena, G., Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells. Am. J. Physiol. Cell Physiol. 304 (2013), C137–C146.
15. [15] Patra, K.C., Hay, N., The pentose phosphate pathway and cancer. Trends Biochem. Sci. 39 (2014), 347–354.
16. [16] Locasale, J.W., Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat. Rev. Cancer 13 (2013), 572–583.
17. [17] Zhang, Z., Apse, K., Pang, J., et al. High glucose inhibits glucose-6-phosphate dehydrogenase via cAMP in aortic endothelial cells. J. Biol. Chem. 275 (2000), 40042–40047.
18. [18] Kruger, N.J., von Schaewen, A., The oxidative pentose phosphate pathway: structure and organisation. Curr. Opin. Plant Biol. 6 (2003), 236–246.
19. [19] Schoors, S., Bruning, U., Missiaen, R., et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature 520 (2015), 192–197.
20. [20] Harjes, U., Bridges, E., McIntyre, A., et al. Fatty acid-binding protein 4, a point of convergence for angiogenic and metabolic signaling pathways in endothelial cells. J. Biol. Chem. 289 (2014), 23168–23176.
21. [21] Wei, X., Schneider, J.G., Shenouda, S.M., et al. De novo lipogenesis maintains vascular homeostasis through endothelial nitric-oxide synthase (eNOS) palmitoylation. J. Biol. Chem. 286 (2011), 2933–2945.
22. [22] Andrew, P.J., Mayer, B., Enzymatic function of nitric oxide synthases. Cardiovasc Res. 43 (1999), 521–531.
23. [23] Davignon, J., Ganz, P., Role of endothelial dysfunction in atherosclerosis. Circulation 109 (2004), 27–32.
24. [24] Kopincova, J., Puzserova, A., Bernatova, I., L-NAME in the cardiovascular system – nitric oxide synthase activator?. Pharmacol. Rep. 64 (2012), 511–520.
25. [25] DeBerardinis, R.J., Cheng, T., Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29 (2010), 313–324.
26. [26] Wilhelm, K., Happel, K., Eelen, G., et al. FOXO1 couples metabolic activity and growth state in the vascular endothelium. Nature 529 (2016), 216–220.
27. [27] Guzik, T.J., Mussa, S., Gastaldi, D., et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105 (2002), 1656–1662.
28. [28] Battault, S., Singh, F., Gayrard, S., et al. Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling. Hypertens. Res. Off. J. Jpn. Soc. Hypertens. 39 (2016), 70–78.
29. [29] Bendall, J.K., Douglas, G., McNeill, E., et al. Tetrahydrobiopterin in cardiovascular health and disease. Antioxid. Redox Signal 20 (2014), 3040–3077.
30. [30] Inoguchi, T., Tsubouchi, H., Etoh, T., et al. A possible target of antioxidative therapy for diabetic vascular complications-vascular NAD(P)H oxidase. Curr. Med. Chem. 10 (2003), 1759–1764.
31. [31] Bedard, K., Krause, K.H., The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol. Rev. 87 (2007), 245–313.
32. [32] Guzik, T.J., Harrison, D.G., Vascular NADPH oxidases as drug targets for novel antioxidant strategies. Drug Discov. Today 11 (2006), 524–533.
33. [33] Baum, C., Johannsen, S.S., Zeller, T., et al. ADMA and arginine derivatives in relation to non-invasive vascular function in the general population. Atherosclerosis 244 (2016), 149–156.
34. [34] Boger, R.H., Asymmetric dimethylarginine: understanding the physiology, genetics, and clinical relevance of this novel biomarker. Proceedings of the 4th International Symposium on ADMA, Pharmacological Research: the Official Journal of the Italian Pharmacological Society, 60, 2009, 447.
35. [35] Lerman, A., Burnett, J.C. Jr., Higano, S.T., et al. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 97 (1998), 2123–2128.
36. [36] Boger, R.H., Bode-Boger, S.M., Szuba, A., et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 98 (1998), 1842–1847.
37. [37] Chan, J.R., Boger, R.H., Bode-Boger, S.M., et al. Asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans. Arterioscler. Thromb. Vasc. Biol. 20 (2000), 1040–1046.
38. [38] Betz, B., Moller-Ehrlich, K., Kress, T., et al. Increased symmetrical dimethylarginine in ischemic acute kidney injury as a causative factor of renal L-arginine deficiency. Transl. Res. 162 (2013), 67–76.
39. [39] Feliers, D., Lee, D.Y., Gorin, Y., et al. Symmetric dimethylarginine alters endothelial nitric oxide activity in glomerular endothelial cells. Cell Signal 27 (2015), 1–5.
40. [40] Siegerink, B., Maas, R., Vossen, C.Y., et al. Asymmetric and symmetric dimethylarginine and risk of secondary cardiovascular disease events and mortality in patients with stable coronary heart disease: the KAROLA follow-up study. Clin. Res. Cardiol. 102 (2013), 193–202.
41. [41] Ozaki, M., Kawashima, S., Yamashita, T., et al. Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice. J. Clin. Invest 110 (2002), 331–340.
42. [42] Laursen, J.B., Somers, M., Kurz, S., et al. Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation 103 (2001), 1282–1288.
43. [43] Desai, C.K., Huang, J., Lokhandwala, A., et al. The role of vitamin supplementation in the prevention of cardiovascular disease events. Clin. Cardiol. 37 (2014), 576–581.
44. [44] Hickey, S.E., Curry, C.J., Toriello, H.V., ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet. Med. 15 (2013), 153–156.
45. [45] Kelly, P.J., Rosand, J., Kistler, J.P., et al. Homocysteine, MTHFR 677C–>T polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology 59 (2002), 529–536.
46. [46] Klerk, M., Verhoef, P., Clarke, R., et al. MTHFR 677C–>T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 288 (2002), 2023–2031.
47. [47] Damico, R., Zulueta, J.J., Hassoun, P.M., Pulmonary endothelial cell NOX. Am. J. Respir. Cell Mol. Biol. 47 (2012), 129–139.
48. [48] Drummond, G.R., Sobey, C.G., Endothelial NADPH oxidases: which NOX to target in vascular disease?. Trends Endocrinol. Metab. 25 (2014), 452–463.
49. [49] Oak, J.H., Cai, H., Attenuation of angiotensin II signaling recouples eNOS and inhibits nonendothelial NOX activity in diabetic mice. Diabetes 56 (2007), 118–126.
50. [50] Menden, H., Welak, S., Cossette, S., et al. Lipopolysaccharide (LPS)-mediated angiopoietin-2-dependent autocrine angiogenesis is regulated by NADPH oxidase 2 (Nox2) in human pulmonary microvascular endothelial cells. J. Biol. Chem. 290 (2015), 5449–5461.
51. [51] Diebold, I., Petry, A., Sabrane, K., et al. The HIF1 target gene NOX2 promotes angiogenesis through urotensin-II. J. Cell Sci. 125 (2012), 956–964.
52. [52] Inoguchi, T., Li, P., Umeda, F., et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C–dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49 (2000), 1939–1945.
53. [53] Shao, B., Bayraktutan, U., Hyperglycaemia promotes human brain microvascular endothelial cell apoptosis via induction of protein kinase C-ssI and prooxidant enzyme NADPH oxidase. Redox Biol. 2 (2014), 694–701.
54. [54] Gorlach, A., Brandes, R.P., Nguyen, K., et al. A gp91phox containing NADPH oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall. Circ. Res. 87 (2000), 26–32.
55. [55] Hwang, J., Ing, M.H., Salazar, A., et al. Pulsatile versus oscillatory shear stress regulates NADPH oxidase subunit expression: implication for native LDL oxidation. Circ. Res. 93 (2003), 1225–1232.
56. [56] Siu, K.L., Gao, L., Cai, H., Differential roles of protein complexes NOX1-NOXO1 and NOX2-p47phox in mediating endothelial redox responses to oscillatory and unidirectional laminar shear stress. J. Biol. Chem. 291 (2016), 8653–8662.
57. [57] Zhou, X., Chen, M., Zeng, X., et al. Resveratrol regulates mitochondrial reactive oxygen species homeostasis through Sirt3 signaling pathway in human vascular endothelial cells. Cell Death Dis., 5, 2014, e1576.
58. [58] Xie, L., Feng, H., Li, S., et al. SIRT3 mediates the antioxidant effect of hydrogen sulfide in endothelial cells. Antioxid. Redox Signal 24 (2016), 329–343.
59. [59] Liu, G., Cao, M., Xu, Y., et al. SIRT3 protects endothelial cells from high glucose-induced cytotoxicity. Int. J. Clin. Exp. Pathol. 8 (2015), 353–360.
60. [60] Agarwal, B., Campen, M.J., Channell, M.M., et al. Resveratrol for primary prevention of atherosclerosis: clinical trial evidence for improved gene expression in vascular endothelium. Int. J. Cardiol. 166 (2013), 246–248.
61. [61] Gray, S.P., Di Marco, E., Kennedy, K., et al. Reactive oxygen species can provide atheroprotection via NOX4-dependent inhibition of inflammation and vascular remodeling. Arterioscler. Thromb. Vasc. Biol. 36 (2016), 295–307.
62. [62] Sivitz, W.I., Yorek, M.A., Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid. Redox Signal 12 (2010), 537–577.
63. [63] Griendling, K.K., Sorescu, D., Lassegue, B., et al. Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler. Thromb. Vasc. Biol. 20 (2000), 2175–2183.
64. [64] Du, X., Matsumura, T., Edelstein, D., et al. Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J. Clin. Invest 112 (2003), 1049–1057.
65. [65] Musicki, B., Kramer, M.F., Becker, R.E., et al. Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 11870–11875.
66. [66] Du, X.L., Edelstein, D., Dimmeler, S., et al. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J. Clin. Invest 108 (2001), 1341–1348.
67. [67] Goldin, A., Beckman, J.A., Schmidt, A.M., et al. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114 (2006), 597–605.
68. [68] Inoguchi, T., Battan, R., Handler, E., et al. Preferential elevation of protein kinase C isoform beta II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. Proc. Natl. Acad. Sci. U. S. A. 89 (1992), 11059–11063.
69. [69] Leopold, J.A., Walker, J., Scribner, A.W., et al. Glucose-6-phosphate dehydrogenase modulates vascular endothelial growth factor-mediated angiogenesis. J. Biol. Chem. 278 (2003), 32100–32106.
70. [70] Zhang, H., Forman, H.J., Glutathione synthesis and its role in redox signaling. Semin. Cell Dev. Biol. 23 (2012), 722–728.
71. [71] Park, J.B., Nagar, H., Choi, S., et al. IDH2 deficiency impairs mitochondrial function in endothelial cells and endothelium-dependent vasomotor function. Free Radic. Biol. Med. 94 (2016), 36–46.
72. [72] Boger, R.H., Sydow, K., Borlak, J., et al. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ. Res. 87 (2000), 99–105.
73. [73] Fang, L., Choi, S.H., Baek, J.S., et al. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature 498 (2013), 118–122.
74. [74] Ohkawara, H., Ishibashi, T., Saitoh, S., et al. Preventive effects of pravastatin on thrombin-triggered vascular responses via Akt/eNOS and RhoA/Rac1 pathways in vivo. Cardiovasc Res. 88 (2010), 492–501.
75. [75] Laufs, U., La Fata, V., Plutzky, J., et al. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97 (1998), 1129–1135.
76. [76] Mugoni, V., Postel, R., Catanzaro, V., et al. Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis. Cell 152 (2013), 504–518.
77. [77] Tsai, K.L., Huang, Y.H., Kao, C.L., et al. A novel mechanism of coenzyme Q10 protects against human endothelial cells from oxidative stress-induced injury by modulating NO-related pathways. J. Nutr. Biochem. 23 (2012), 458–468.
78. [78] Chew, G.T., Watts, G.F., Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the ‘recoupling hypothesis’. QJM 97 (2004), 537–548.
79. [79] Vaklavas, C., Chatzizisis, Y.S., Ziakas, A., et al. Molecular basis of statin-associated myopathy. Atherosclerosis 202 (2009), 18–28.
80. [80] Antonopoulos, A.S., Margaritis, M., Shirodaria, C., et al. Translating the effects of statins: from redox regulation to suppression of vascular wall inflammation. Thromb. Haemost. 108 (2012), 840–848.
81. [81] Kratzer, A., Giral, H., Landmesser, U., High-density lipoproteins as modulators of endothelial cell functions: alterations in patients with coronary artery disease. Cardiovasc Res. 103 (2014), 350–361.
82. [82] Skalen, K., Gustafsson, M., Rydberg, E.K., et al. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature 417 (2002), 750–754.
83. [83] Stocker, R., Keaney, J.F. Jr., Role of oxidative modifications in atherosclerosis. Physiol. Rev. 84 (2004), 1381–1478.
84. [84] Goyal, T., Mitra, S., Khaidakov, M., et al. Current concepts of the role of oxidized LDL receptors in atherosclerosis. Curr. Atheroscler. Rep. 14 (2012), 150–159.
85. [85] Xu, S., Ogura, S., Chen, J., et al. LOX-1 in atherosclerosis: biological functions and pharmacological modifiers. Cell Mol. Life Sci. 70 (2013), 2859–2872.
86. [86] Sawamura, T., Kume, N., Aoyama, T., et al. An endothelial receptor for oxidized low-density lipoprotein. Nature 386 (1997), 73–77.
87. [87] Mehta, J.L., Li, D.Y., Chen, H.J., et al. Inhibition of LOX-1 by statins may relate to upregulation of eNOS. Biochem. Biophys. Res. Commun. 289 (2001), 857–861.
88. [88] Sugimoto, K., Ishibashi, T., Sawamura, T., et al. LOX-1-MT1-MMP axis is crucial for RhoA and Rac1 activation induced by oxidized low-density lipoprotein in endothelial cells. Cardiovasc Res. 84 (2009), 127–136.
89. [89] Xu, X., Gao, X., Potter, B.J., et al. Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice. Arterioscler. Thromb. Vasc. Biol. 27 (2007), 871–877.
90. [90] Trabetti, E., Biscuola, M., Cavallari, U., et al. On the association of the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction or coronary artery disease. Eur. J. Hum. Genet. 14 (2006), 127–130.
91. [91] Ballinger, S.W., Patterson, C., Knight-Lozano, C.A., et al. Mitochondrial integrity and function in atherogenesis. Circulation 106 (2002), 544–549.
92. [92] Ryoo, S., Lemmon, C.A., Soucy, K.G., et al. Oxidized low-density lipoprotein-dependent endothelial arginase II activation contributes to impaired nitric oxide signaling. Circ. Res. 99 (2006), 951–960.
93. [93] Edsfeldt, A., Duner, P., Stahlman, M., et al. Sphingolipids contribute to human atherosclerotic plaque inflammation. Arterioscler. Thromb. Vasc. Biol. 36 (2016), 1132–1140.
94. [94] Jeong, T., Schissel, S.L., Tabas, I., et al. Increased sphingomyelin content of plasma lipoproteins in apolipoprotein E knockout mice reflects combined production and catabolic defects and enhances reactivity with mammalian sphingomyelinase. J. Clin. Invest 101 (1998), 905–912.
95. [95] Chun, L., Junlin, Z., Aimin, W., et al. Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats. Diabetes Res. Clin. Pract. 93 (2011), 77–85.
96. [96] Zhang, Y., Pan, Y., Bian, Z., et al. Ceramide production mediates aldosterone-induced human umbilical vein endothelial cell (HUVEC) damages. PLoS One, 11, 2016, e0146944.
97. [97] Goldberg, I.J., Bornfeldt, K.E., Lipids and the endothelium: bidirectional interactions. Curr. Atheroscler. Rep., 15, 2013, 365.
98. [98] Rosenson, R.S., Brewer, H.B. Jr., Ansell, B.J., et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat. Rev. Cardiol. 13 (2016), 48–60.
99. [99] Yuhanna, I.S., Zhu, Y., Cox, B.E., et al. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat. Med. 7 (2001), 853–857.
100. [100] Besler, C., Heinrich, K., Rohrer, L., et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J. Clin. Invest 121 (2011), 2693–2708.
101. [101] Sattler, K.J., Elbasan, S., Keul, P., et al. Sphingosine 1-phosphate levels in plasma and HDL are altered in coronary artery disease. Basic Res. Cardiol. 105 (2010), 821–832.
102. [102] Sattler, K., Lehmann, I., Graler, M., et al. HDL-bound sphingosine 1-phosphate (S1P) predicts the severity of coronary artery atherosclerosis. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 34 (2014), 172–184.
103. [103] Poti, F., Simoni, M., Nofer, J.R., Atheroprotective role of high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P). Cardiovasc Res. 103 (2014), 395–404.
104. [104] Tabas, I., Garcia-Cardena, G., Owens, G.K., Recent insights into the cellular biology of atherosclerosis. J. Cell Biol. 209 (2015), 13–22.
105. [105] Parmar, K.M., Larman, H.B., Dai, G., et al. Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J. Clin. Invest 116 (2006), 49–58.
106. [106] de Bruin, R.G., van der Veer, E.P., Prins, J., et al. The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and beta-catenin protein expression. Sci. Rep., 6, 2016, 21643.
107. [107] Boon, R.A., Leyen, T.A., Fontijn, R.D., et al. KLF2-induced actin shear fibers control both alignment to flow and JNK signaling in vascular endothelium. Blood 115 (2010), 2533–2542.
108. [108] Novodvorsky, P., Chico, T.J., The role of the transcription factor KLF2 in vascular development and disease. Prog. Mol. Biol. Transl. Sci. 124 (2014), 155–188.
109. [109] Kumar, A., Kumar, S., Vikram, A., et al. Histone and DNA methylation-mediated epigenetic downregulation of endothelial Kruppel-like factor 2 by low-density lipoprotein cholesterol. Arterioscler. Thromb. Vasc. Biol. 33 (2013), 1936–1942.
110. [110] Loyer, X., Potteaux, S., Vion, A.C., et al. Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ. Res. 114 (2014), 434–443.
111. [111] Chen, Z., Wen, L., Martin, M., et al. Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a. Circulation 131 (2015), 805–814.
112. [112] Doddaballapur, A., Michalik, K.M., Manavski, Y., et al. Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3. Arterioscler. Thromb. Vasc. Biol. 35 (2015), 137–145.
113. [113] Dane, M.J., van den Berg, B.M., Lee, D.H., et al. A microscopic view on the renal endothelial glycocalyx. Am. J. Physiol. Ren. Physiol. 308 (2015), F956–F966.
114. [114] Tarbell, J.M., Cancel, L.M., The glycocalyx and its significance in human medicine. J. Intern Med. 280 (2016), 97–113.
115. [115] Ebong, E.E., Lopez-Quintero, S.V., Rizzo, V., et al. Shear-induced endothelial NOS activation and remodeling via heparan sulfate, glypican-1, and syndecan-1. Integr. Biol. Quant. Biosci. Nano Macro 6 (2014), 338–347.
116. [116] Kolarova, H., Ambruzova, B., Svihalkova Sindlerova, L., et al. Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediat. Inflamm., 2014, 2014, 694312.
117. [117] Becker, B.F., Jacob, M., Leipert, S., et al. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br. J. Clin. Pharmacol. 80 (2015), 389–402.
118. [118] Pahwa, R., Nallasamy, P., Jialal, I., Toll-like receptors 2 and 4 mediate hyperglycemia induced macrovascular aortic endothelial cell inflammation and perturbation of the endothelial glycocalyx. J. Diabetes Complicat. 30 (2016), 563–572.
119. [119] Singh, A., Ramnath, R.D., Foster, R.R., et al. Reactive oxygen species modulate the barrier function of the human glomerular endothelial glycocalyx. PLoS One, 8, 2013, e55852.
120. [120] Kumagai, R., Lu, X., Kassab, G.S., Role of glycocalyx in flow-induced production of nitric oxide and reactive oxygen species. Free Radic. Biol. Med. 47 (2009), 600–607.
121. [121] Miranda, C.H., de Carvalho Borges, M., Schmidt, A., et al. Evaluation of the endothelial glycocalyx damage in patients with acute coronary syndrome. Atherosclerosis 247 (2016), 184–188.
122. [122] Dicker, K.T., Gurski, L.A., Pradhan-Bhatt, S., et al. Hyaluronan: a simple polysaccharide with diverse biological functions. Acta Biomater. 10 (2014), 1558–1570.
123. [123] Vigetti, D., Viola, M., Karousou, E., et al. Metabolic control of hyaluronan synthases. Matrix Biol. 35 (2014), 8–13.
124. [124] Kanthi, Y., Hyman, M.C., Liao, H., et al. Flow-dependent expression of ectonucleotide tri(di)phosphohydrolase-1 and suppression of atherosclerosis. J. Clin. Invest 125 (2015), 3027–3036.
125. [125] Wu, C., Huang, R.T., Kuo, C.H., et al. Mechanosensitive PPAP2B regulates endothelial responses to atherorelevant hemodynamic forces. Circ. Res. 117 (2015), e41–53.
126. [126] Schunkert, H., Konig, I.R., Kathiresan, S., et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat. Genet. 43 (2011), 333–338.
127. [127] Pushpakumar, S., Kundu, S., Sen, U., Endothelial dysfunction: the link between homocysteine and hydrogen sulfide. Curr. Med. Chem. 21 (2014), 3662–3672.
128. [128] Wang, R., Szabo, C., Ichinose, F., et al. The role of H2S bioavailability in endothelial dysfunction. Trends Pharmacol. Sci. 36 (2015), 568–578.
129. [129] Coletta, C., Modis, K., Szczesny, B., et al. Regulation of vascular tone, angiogenesis and cellular bioenergetics by the 3-mercaptopyruvate sulfurtransferase/H2S pathway: functional impairment by hyperglycemia and restoration by DL-alpha-lipoic acid. Mol. Med. 21 (2015), 1–14.
130. [130] Xu, S., Liu, Z., Liu, P., Targeting hydrogen sulfide as a promising therapeutic strategy for atherosclerosis. Int. J. Cardiol. 172 (2014), 313–317.
131. [131] Mani, S., Untereiner, A., Wu, L., et al. Hydrogen sulfide and the pathogenesis of atherosclerosis. Antioxid. Redox Signal 20 (2014), 805–817.
132. [132] Qi, L., Qi, Q., Prudente, S., et al. Association between a genetic variant related to glutamic acid metabolism and coronary heart disease in individuals with type 2 diabetes. JAMA 310 (2013), 821–828.
133. [133] Lomivorotov, V.V., Efremov, S.M., Shmirev, V.A., et al. Glutamine is cardioprotective in patients with ischemic heart disease following cardiopulmonary bypass. Heart Surg. Forum. 14 (2011), E384–E388.
134. [134] Sufit, A., Weitzel, L.B., Hamiel, C., et al. Pharmacologically dosed oral glutamine reduces myocardial injury in patients undergoing cardiac surgery: a randomized pilot feasibility trial. JPEN J. Parenter. Enter. Nutr. 36 (2012), 556–561.
135. [135] Lu, Z., Li, Y., Jin, J., et al. GPR40/FFA1 and neutral sphingomyelinase are involved in palmitate-boosted inflammatory response of microvascular endothelial cells to LPS. Atherosclerosis 240 (2015), 163–173.
136. [136] Toral, M., Romero, M., Jimenez, R., et al. Carnitine palmitoyltransferase-1 up-regulation by PPAR-beta/delta prevents lipid-induced endothelial dysfunction. Clin. Sci. Lond 129 (2015), 823–837.
137. [137] Harjes, U., Kalucka, J., Carmeliet, P., Targeting fatty acid metabolism in cancer and endothelial cells. Crit. Rev. Oncol. Hematol. 97 (2016), 15–21.
138. [138] Tang, W.H., Hazen, S.L., The contributory role of gut microbiota in cardiovascular disease. J. Clin. Invest 124 (2014), 4204–4211.
139. [139] Wang, Z., Roberts, A.B., Buffa, J.A., et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163 (2015), 1585–1595.
140. [140] Seldin, M.M., Meng, Y., Qi, H., et al. Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-kappaB. J. Am. Heart Assoc., 2016, 5.
141. [141] Meijers, B.K., Evenepoel, P., The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol. Dial. Transpl. 26 (2011), 759–761.
142. [142] Meijers, B.K., Van Kerckhoven, S., Verbeke, K., et al. The uremic retention solute p-cresyl sulfate and markers of endothelial damage. Am. J. Kidney Dis. 54 (2009), 891–901.
143. [143] Meijers, B.K., Claes, K., Bammens, B., et al. p-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin. J. Am. Soc. Nephrol. 5 (2010), 1182–1189.
144. [144] Jing, Y.J., Ni, J.W., Ding, F.H., et al. p-Cresyl sulfate is associated with carotid arteriosclerosis in hemodialysis patients and promotes atherogenesis in apoE-/- mice. Kidney Int. 89 (2016), 439–449.
145. [145] Koppe, L., Pillon, N.J., Vella, R.E., et al. p-Cresyl sulfate promotes insulin resistance associated with CKD. J. Am. Soc. Nephrol. 24 (2013), 88–99.
146. [146] Dou, L., Jourde-Chiche, N., Faure, V., et al. The uremic solute indoxyl sulfate induces oxidative stress in endothelial cells. J. Thromb. Haemost. 5 (2007), 1302–1308.
147. [147] Dou, L., Sallee, M., Cerini, C., et al. The cardiovascular effect of the uremic solute indole-3 acetic acid. J. Am. Soc. Nephrol. 26 (2015), 876–887.
148. [148] Yu, M., Kim, Y.J., Kang, D.H., Indoxyl sulfate-induced endothelial dysfunction in patients with chronic kidney disease via an induction of oxidative stress. Clin. J. Am. Soc. Nephrol. 6 (2011), 30–39.
149. [149] Yin, M., Loyer, X., Boulanger, C.M., Extracellular vesicles as new pharmacological targets to treat atherosclerosis. Eur. J. Pharmacol. 763 (2015), 90–103.
150. [150] Jansen, F., Yang, X., Franklin, B.S., et al. High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation. Cardiovasc Res. 98 (2013), 94–106.
151. [151] Jansen, F., Yang, X., Hoelscher, M., et al. Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles. Circulation 128 (2013), 2026–2038.
152. [152] Pirro, M., Schillaci, G., Paltriccia, R., et al. Increased ratio of CD31+/CD42- microparticles to endothelial progenitors as a novel marker of atherosclerosis in hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 26 (2006), 2530–2535.