Hyperhomocysteinemia attenuates angiogenesis through reduction of HIF-1α and PGC-1α levels in muscle fibers during hindlimb ischemia

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 306, Issue 8, 2014, Pages

  Veeranki, Sudhakar ^a   Givvimani, Srikanth ^a   Pushpakumar, Sathnur ^a   Tyagi, Suresh C ^a  

^a University of Louisville School of Medicine   (United States)

Author keywords

Akt; Angiogenesis; Atrogin 1; CD31; Hyperhomocysteinemia; Hypoxia inducible factor; Ischemia; Leptin; Muscle ring finger 1; Peroxisome proliferator activated receptor coactivator 1 ; Skeletal muscle; Vascular endothelial growth factor

Indexed keywords

HYPOXIA INDUCIBLE FACTOR 1ALPHA; LEPTIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; UBIQUITIN PROTEIN LIGASE; VASCULOTROPIN;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; HINDLIMB ISCHEMIA; HYPERHOMOCYSTEINEMIA; LIMB ISCHEMIA; MALE; MOUSE; MUSCLE ATROPHY; MUSCLE CELL; MUSCLE FUNCTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; TISSUE PERFUSION;

AKT; ANGIOGENESIS; ATROGIN-1; CD31; HYPERHOMOCYSTEINEMIA; HYPOXIA-INDUCIBLE FACTOR; ISCHEMIA; LEPTIN; MUSCLE RING FINGER-1; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-Γ COACTIVATOR-1Α; SKELETAL MUSCLE; VASCULAR ENDOTHELIAL GROWTH FACTOR;

ANIMALS; BEHAVIOR, ANIMAL; CYSTATHIONINE BETA-SYNTHASE; FEMORAL ARTERY; GENE EXPRESSION; HINDLIMB; HYPERHOMOCYSTEINEMIA; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; ISCHEMIA; LIGATION; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MUSCLE PROTEINS; MUSCLE, SKELETAL; NEOVASCULARIZATION, PHYSIOLOGIC; PROTO-ONCOGENE PROTEINS C-AKT; RNA, MESSENGER; SKP CULLIN F-BOX PROTEIN LIGASES; SWIMMING; TRANSCRIPTION FACTORS; UBIQUITIN-PROTEIN LIGASES; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84900818850     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00003.2014     Document Type: Article

References (55)

1. Andras A, Stansby G, Hansrani M. Homocysteine lowering interventions for peripheral arterial disease and bypass grafts. Cochrane Database Syst Rev 7: CD003285, 2013.
2. Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala SM, Baek KH, Rosenzweig A, Spiegelman BM. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α. Nature 451: 1008-1012, 2008.
3. Beard RS Jr, Bearden SE. Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research. Am J Physiol Heart Circ Physiol 300: H13-H26, 2011.
4. Birot OJ, Koulmann N, Peinnequin A, Bigard XA. Exercise-induced expression of vascular endothelial growth factor mRNA in rat skeletal muscle is dependent on fibre type. J Physiol 552: 213-221, 2003.
5. Bosch-Marce M, Pola R, Wecker AB, Silver M, Weber A, Luedemann C, Curry C, Murayama T, Kearney M, Yoon YS, Malinow MR, Asahara T, Isner JM, Losordo DW. Hyperhomocyst(e)inemia impairs angiogenesis in a murine model of limb ischemia. Vasc Med 10: 15-22, 2005.
6. Conde E, Alegre L, Blanco-Sanchez I, Saenz-Morales D, Aguado-Fraile E, Ponte B, Ramos E, Saiz A, Jimenez C, Ordonez A, Lopez-Cabrera M, del Peso L, de Landazuri MO, Liano F, Selgas R, Sanchez-Tomero JA, Garcia-Bermejo ML. Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival. PLoS One 7: e33258, 2012.
7. Duan J, Murohara T, Ikeda H, Sasaki K, Shintani S, Akita T, Shimada T, Imaizumi T. Hyperhomocysteinemia impairs angiogenesis in response to hindlimb ischemia. Arterioscler Thromb Vasc Biol 20: 2579-2585, 2000.
8. Frey SP, Jansen H, Raschke MJ, Meffert RH, Ochman S. VEGF improves skeletal muscle regeneration after acute trauma and reconstruction of the limb in a rabbit model. Clin Orthop Relat Res 470: 3607-3614, 2012.
9. Gaugler M, Brown A, Merrell E, DiSanto-Rose M, Rathmacher JA, Reynolds TH. PKB signaling and atrogene expression in skeletal muscle of aged mice. J Appl Physiol 111: 192-199, 2011.
10. Gibson JB, Carson NA, Neill DW. Pathological findings in homocystinuria. J Clin Pathol 17: 427-437, 1964.
11. Givvimani S, Munjal C, Tyagi N, Sen U, Metreveli N, Tyagi SC. Mitochondrial division/mitophagy inhibitor (Mdivi) ameliorates pressure overload induced heart failure. PLoS One 7: e32388, 2012.
12. Givvimani S, Sen U, Tyagi N, Munjal C, Tyagi SC. X-ray imaging of differential vascular density in MMP-9-/-, PAR-1-/+, hyperhomocysteinemic (CBS-/+) and diabetic (Ins2-/+) mice. Arch Physiol Biochem 117: 1-7, 2011.
13. Grosfeld A, Andre J, Hauguel-De Mouzon S, Berra E, Pouyssegur J, Guerre-Millo M. Hypoxia-inducible factor 1 transactivates the human leptin gene promoter. J Biol Chem 277: 42953-42957, 2002.
14. Harada H, Itasaka S, Kizaka-Kondoh S, Shibuya K, Morinibu A, Shinomiya K, Hiraoka M. The Akt/mTOR pathway assures the synthesis of HIF-1α protein in a glucose-and reoxygenation-dependent manner in irradiated tumors. J Biol Chem 284: 5332-5342, 2009.
15. Hiasa K, Ishibashi M, Ohtani K, Inoue S, Zhao Q, Kitamoto S, Sata M, Ichiki T, Takeshita A, Egashira K. Gene transfer of stromal cellderived factor-1α enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation 109: 2454-2461, 2004.
16. Hirota K, Semenza GL. Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev Oncol Hematol 59: 15-26, 2006.
17. Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation 101: 1506-1511, 2000.
18. Hudson CC, Liu M, Chiang GG, Otterness DM, Loomis DC, Kaper F, Giaccia AJ, Abraham RT. Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol Cell Biol 22: 7004-7014, 2002.
19. Ishii I, Akahoshi N, Yamada H, Nakano S, Izumi T, Suematsu M. Cystathionine γ-lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. J Biol Chem 285: 26358-26368, 2010.
20. Jager S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proc Natl Acad Sci USA 104: 12017-12022, 2007.
21. Kado DM, Bucur A, Selhub J, Rowe JW, Seeman T. Homocysteine levels and decline in physical function: MacArthur Studies of Successful Aging. Am J Med 113: 537-542, 2002.
22. Kalra BR, Ghose S, Sood NN. Homocystinuria with bilateral absolute glaucoma. Ind J Ophthalmol 33: 195-197, 1985.
23. Karkkainen AM, Kotimaa A, Huusko J, Kholova I, Heinonen SE, Stefanska A, Dijkstra MH, Purhonen H, Hamalainen E, Makinen PI, Turunen MP, Yla-Herttuala S. Vascular endothelial growth factor-D transgenic mice show enhanced blood capillary density, improved postischemic muscle regeneration, and increased susceptibility to tumor formation. Blood 113: 4468-4475, 2009.
24. Khandanpour N, Loke YK, Meyer FJ, Jennings B, Armon MP. Homocysteine and peripheral arterial disease: systematic review and meta-analysis. Eur J Vasc Endovasc Surg 38: 316-322, 2009.
25. Lee I, Lee H, Kim JM, Chae EH, Kim SJ, Chang N. Short-term hyperhomocysteinemia-induced oxidative stress activates retinal glial cells and increases vascular endothelial growth factor expression in rat retina. Biosci Biotechnol Biochem 71: 1203-1210, 2007.
26. Limbourg A, Korff T, Napp LC, Schaper W, Drexler H, Limbourg FP. Evaluation of postnatal arteriogenesis and angiogenesis in a mouse model of hind-limb ischemia. Nat Prot 4: 1737-1746, 2009.
27. Machens HG, Grzybowski S, Bucsky B, Spanholtz T, Niedworok C, Maichle A, Stockelhuber B, Condurache A, Liu F, Egana JT, Kaun M, Mailander P, Aach T. A technique to detect and to quantify fasciocutaneous blood vessels in small laboratory animals ex vivo. J Surg Res 131: 91-96, 2006.
28. Maeda M, Yamamoto I, Fujio Y, Azuma J. Homocysteine induces vascular endothelial growth factor expression in differentiated THP-1 macrophages. Biochim Biophys Acta 1623: 41-46, 2003.
29. Maron BA, Loscalzo J. The treatment of hyperhomocysteinemia. Annu Rev Med 60: 39-54, 2009.
30. McClung JM, McCord TJ, Keum S, Johnson S, Annex BH, Marchuk DA, Kontos CD. Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice. Am J Pathol 180: 2156-2169, 2012.
31. Miller A, Mujumdar V, Shek E, Guillot J, Angelo M, Palmer L, Tyagi SC. Hyperhomocyst(e)inemia induces multiorgan damage. Heart Vessels 15: 135-143, 2000.
32. Niiyama H, Huang NF, Rollins MD, Cooke JP. Murine model of hindlimb ischemia. J Vis Exp: 1035, 2009.
33. Olfert IM, Howlett RA, Tang K, Dalton ND, Gu Y, Peterson KL, Wagner PD, Breen EC. Muscle-specific VEGF deficiency greatly reduces exercise endurance in mice. J Physiol 587: 1755-1767, 2009.
34. Pajusola K, Kunnapuu J, Vuorikoski S, Soronen J, Andre H, Pereira T, Korpisalo P, Yla-Herttuala S, Poellinger L, Alitalo K. Stabilized HIF-1α is superior to VEGF for angiogenesis in skeletal muscle via adeno-associated virus gene transfer. FASEB J 19: 1365-1367, 2005.
35. Park HY, Kwon HM, Lim HJ, Hong BK, Lee JY, Park BE, Jang Y, Cho SY, Kim HS. Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro. Exp Mol Med 33: 95-102, 2001.
36. Raschke S, Eckardt K, Bjorklund Holven K, Jensen J, Eckel J. Identification and validation of novel contraction-regulated myokines released from primary human skeletal muscle cells. PLoS One 8: e62008, 2013.
37. Richardson RS, Wagner H, Mudaliar SR, Henry R, Noyszewski EA, Wagner PD. Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise. Am J Physiol Heart Circ Physiol 277: H2247-H2252, 1999.
38. Richardson RS, Wagner H, Mudaliar SR, Saucedo E, Henry R, Wagner PD. Exercise adaptation attenuates VEGF gene expression in human skeletal muscle. Am J Physiol Heart Circ Physiol 279: H772-H778, 2000.
39. Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117: 399-412, 2004.
40. Sarkar K, Fox-Talbot K, Steenbergen C, Bosch-Marce M, Semenza GL. Adenoviral transfer of HIF-1α enhances vascular responses to critical limb ischemia in diabetic mice. Proc Natl Acad Sci USA 106: 18769-18774, 2009.
41. Semenza GL. Pulmonary vascular responses to chronic hypoxia mediated by hypoxia-inducible factor 1. Proc Am Thorac Soc 2: 68-70, 2005.
42. Sen U, Sathnur PB, Kundu S, Givvimani S, Coley DM, Mishra PK, Qipshidze N, Tyagi N, Metreveli N, Tyagi SC. Increased endogenous H2S generation by CBS, CSE, and 3MST gene therapy improves ex vivo renovascular relaxation in hyperhomocysteinemia. Am J Physiol Cell Physiol 303: C41-C51, 2012.
43. Springer ML, Ozawa CR, Banfi A, Kraft PE, Ip TK, Brazelton TR, Blau HM. Localized arteriole formation directly adjacent to the site of VEGF-induced angiogenesis in muscle. Mol Ther 7: 441-449, 2003.
44. Stroka DM, Burkhardt T, Desbaillets I, Wenger RH, Neil DA, Bauer C, Gassmann M, Candinas D. HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia. FASEB J 15: 2445-2453, 2001.
45. Tadaishi M, Miura S, Kai Y, Kano Y, Oishi Y, Ezaki O. Skeletal muscle-specific expression of PGC-1α-β, an exercise-responsive isoform, increases exercise capacity and peak oxygen uptake. PLoS One 6: e28290, 2011.
46. Tuomisto TT, Rissanen TT, Vajanto I, Korkeela A, Rutanen J, Yla-Herttuala S. HIF-VEGF-VEGFR-2, TNF-α and IGF pathways are upregulated in critical human skeletal muscle ischemia as studied with DNA array. Atherosclerosis 174: 111-120, 2004.
47. Tyagi N, Qipshidze N, Sen U, Rodriguez W, Ovechkin A, Tyagi SC. Cystathionine β synthase gene dose dependent vascular remodeling in murine model of hyperhomocysteinemia. Int J Physiol Pathophysiol Pharmacol 3: 210-222, 2011.
48. Veeranki S, Tyagi SC. Defective homocysteine metabolism: potential implications for skeletal muscle malfunction. Int J Mol Sci 14: 15074-15091, 2013.
49. Wagner PD, Olfert IM, Tang K, Breen EC. Muscle-targeted deletion of VEGF and exercise capacity in mice. Respir Physiol Neurobiol 151: 159-166, 2006.
50. Watanabe M, Osada J, Aratani Y, Kluckman K, Reddick R, Malinow MR, Maeda N. Mice deficient in cystathionine β-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci USA 92: 1585-1589, 1995.
51. Wong YY, Almeida OP, McCaul KA, Yeap BB, Hankey GJ, Flicker L. Homocysteine, frailty, and all-cause mortality in older men: the health in men study. J Gerontol A Biol Sci Med Sci 68: 590-598, 2013.
52. Yan TT, Li Q, Zhang XH, Wu WK, Sun J, Li L, Zhang Q, Tan HM. Homocysteine impaired endothelial function through compromised vascular endothelial growth factor/Akt/endothelial nitric oxide synthase signalling. Clin Exp Pharmacol Physiol 37: 1071-1077, 2010.
53. Yap S, Naughten ER, Wilcken B, Wilcken DE, Boers GH. Vascular complications of severe hyperhomocysteinemia in patients with homocystinuria due to cystathionine beta-synthase deficiency: effects of homocysteine-lowering therapy. Semin Thromb Hemost 26: 335-340, 2000.
54. Zhu L, Wang Q, Zhang L, Fang Z, Zhao F, Lv Z, Gu Z, Zhang J, Wang J, Zen K, Xiang Y, Wang D, Zhang CY. Hypoxia induces PGC-1α expression and mitochondrial biogenesis in the myocardium of TOF patients. Cell Res 20: 676-687, 2010.
55. Zwetsloot KA, Westerkamp LM, Holmes BF, Gavin TP. AMPK regulates basal skeletal muscle capillarization and VEGF expression, but is not necessary for the angiogenic response to exercise. J Physiol 586: 6021-6035, 2008.