Skip to main content
SpringerLink
Log in

Vascular Remodeling: Homocysteine and Diabetes

  • Chapter
  • First Online:
Book cover Mechanisms of Vascular Defects in Diabetes Mellitus

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 17))

  • 1331 Accesses

Abstract

Remodeling of the vascular wall contributes to hypertension in humans owing to changes in vessel diameter and thickening of intimal and medial layers of the vascular wall promoting total peripheral resistance. This chapter describes the mechanisms that contribute to the pathogenesis of arterial remodeling. It also highlights endothelial dysfunction observed in arteries of hypertensive subjects and role of elevated homocysteine in facilitating peripheral vascular remodeling. The chapter also describes metabolism of homocysteine and how it functions as an independent risk factor of atherothrombotic complications of vascular disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Schiffrin EL (2015) Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension. Clin Invest Med 38(6):E394–E402

    Article  PubMed  Google Scholar 

  2. van Varik BJ, Rennenberg RJ, Reutelingsperger CP, Kroon AA, de Leeuw PW, Schurgers LJ (2012) Mechanisms of arterial remodeling: lessons from genetic diseases. Front Genet 3:290. doi:10.3389/fgene.2012.00290

    PubMed  PubMed Central  Google Scholar 

  3. van den Akker J, Schoorl MJ, Bakker EN, Vanbavel E (2010) Small artery remodeling: current concepts and questions. J Vasc Res 47(3):183–202. doi:10.1159/000255962

    Article  PubMed  Google Scholar 

  4. Iyemere VP, Proudfoot D, Weissberg PL, Shanahan CM (2006) Vascular smooth muscle cell phenotypic plasticity and the regulation of vascular calcification. J Intern Med 260(3):192–210. doi:10.1111/j.1365-2796.2006.01692.x

    Article  CAS  PubMed  Google Scholar 

  5. van Eys GJ, Niessen PM, Rensen SS (2007) Smoothelin in vascular smooth muscle cells. Trends Cardiovasc Med 17(1):26–30. doi:10.1016/j.tcm.2006.11.001

    Article  PubMed  Google Scholar 

  6. Willis AI, Pierre-Paul D, Sumpio BE, Gahtan V (2004) Vascular smooth muscle cell migration: current research and clinical implications. Vasc Endovasc Surg 38(1):11–23

    Article  CAS  Google Scholar 

  7. Shanahan CM, Cary NR, Metcalfe JC, Weissberg PL (1994) High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. J Clin Invest 93(6):2393–2402. doi:10.1172/JCI117246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Xu J, Shi GP (2014) Vascular wall extracellular matrix proteins and vascular diseases. Biochim Biophys Acta 1842(11):2106–2119. doi:10.1016/j.bbadis.2014.07.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nichols WW (2005) Clinical measurement of arterial stiffness obtained from noninvasive pressure waveforms. Am J Hypertens 18(1 Pt 2):3S–10S. doi:10.1016/j.amjhyper.2004.10.009

    Article  PubMed  Google Scholar 

  10. Intengan HD, Schiffrin EL (2000) Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants. Hypertension 36(3):312–318

    Article  CAS  PubMed  Google Scholar 

  11. Intengan HD, Schiffrin EL (2001) Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension 38(3 Pt 2):581–587

    Article  CAS  PubMed  Google Scholar 

  12. Csiszar A, Lehoux S, Ungvari Z (2009) Hemodynamic forces, vascular oxidative stress, and regulation of BMP-2/4 expression. Antioxid Redox Signal 11(7):1683–1697. doi:10.1089/ARS.2008.2401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Urschel K, Cicha I, Daniel WG, Garlichs CD (2012) Shear stress patterns affect the secreted chemokine profile in endothelial cells. Clin Hemorheol Microcirc 50(1–2):143–152. doi:10.3233/CH-2011-1450

    PubMed  Google Scholar 

  14. Endemann DH, Schiffrin EL (2004) Endothelial dysfunction. J Am Soc Nephrol 15(8):1983–1992. doi:10.1097/01.ASN.0000132474.50966.DA

    Article  CAS  PubMed  Google Scholar 

  15. Familtseva A, Kalani A, Chaturvedi P, Tyagi N, Metreveli N, Tyagi SC (2014) Mitochondrial mitophagy in mesenteric artery remodeling in hyperhomocysteinemia. Physiol Reports 2(4):e00283. doi:10.14814/phy2.283

    Article  Google Scholar 

  16. Mazza A, Cuppini S, Schiavon L, Zuin M, Ravenni R, Balbi G, Montemurro D, Opocher G, Pelizzo MR, Colletti PM, Rubello D (2014) Hyperhomocysteinemia is an independent predictor of sub-clinical carotid vascular damage in subjects with grade-1 hypertension. Endocrine 46(2):340–346. doi:10.1007/s12020-013-0063-3

    Article  CAS  PubMed  Google Scholar 

  17. Nelson J, Wu Y, Jiang X, Berretta R, Houser S, Choi E, Wang J, Huang J, Yang X, Wang H (2015) Hyperhomocysteinemia suppresses bone marrow CD34+/VEGF receptor 2+ cells and inhibits progenitor cell mobilization and homing to injured vasculature-a role of beta1-integrin in progenitor cell migration and adhesion. FASEB J 29(7):3085–3099. doi:10.1096/fj.14-267989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Saha S, Chakraborty PK, Xiong X, Dwivedi SK, Mustafi SB, Leigh NR, Ramchandran R, Mukherjee P, Bhattacharya R (2016) Cystathionine beta-synthase regulates endothelial function via protein S-sulfhydration. FASEB J 30(1):441–456. doi:10.1096/fj.15-278648

    Article  CAS  PubMed  Google Scholar 

  19. Hankey GJ, Eikelboom JW (1999) Homocysteine and vascular disease. Lancet 354(9176):407–413. doi:10.1016/S0140-6736(98)11058-9

    Article  CAS  PubMed  Google Scholar 

  20. Sen U, Pushpakumar SB, Amin MA, Tyagi SC (2014) Homocysteine in renovascular complications: hydrogen sulfide is a modulator and plausible anaerobic ATP generator. Nitric Oxide 41:27–37. doi:10.1016/j.niox.2014.06.006

    Article  CAS  PubMed  Google Scholar 

  21. Szegedi SS, Castro CC, Koutmos M, Garrow TA (2008) Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-homocysteine methyltransferase. J Biol Chem 283(14):8939–8945. doi:10.1074/jbc.M710449200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Garrow TA (1996) Purification, kinetic properties, and cDNA cloning of mammalian betaine-homocysteine methyltransferase. J Biol Chem 271(37):22831–22838

    Article  CAS  PubMed  Google Scholar 

  23. Zhang W, He H, Wang H, Wang S, Li X, Liu Y, Jiang H, Jiang H, Yan Y, Wang Y, Liu X (2013) Activation of transsulfuration pathway by salvianolic acid a treatment: a homocysteine-lowering approach with beneficial effects on redox homeostasis in high-fat diet-induced hyperlipidemic rats. Nutr Metab 10(1):68. doi:10.1186/1743-7075-10-68

    Article  Google Scholar 

  24. Holst-Schumacher I, Monge-Rojas R, Cambronero-Gutierrez P, Brenes G (2005) Genetic, dietary, and other lifestyle determinants of serum homocysteine levels in young adults in Costa Rica. Revista panamericana de salud publica = Pan Am J Pub Health 17(4):263–270

    Article  Google Scholar 

  25. Yang B, Fan S, Zhi X, Wang Y, Wang Y, Zheng Q, Sun G (2015) Prevalence of hyperhomocysteinemia in China: a systematic review and meta-analysis. Forum Nutr 7(1):74–90. doi:10.3390/nu7010074

    Google Scholar 

  26. Jacques PF, Rosenberg IH, Rogers G, Selhub J, Bowman BA, Gunter EW, Wright JD, Johnson CL (1999) Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr 69(3):482–489

    CAS  PubMed  Google Scholar 

  27. Selhub J (2006) The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr 136(6 Suppl):1726S–1730S

    CAS  PubMed  Google Scholar 

  28. Giltay EJ, Hoogeveen EK, Elbers JM, Gooren LJ, Asscheman H, Stehouwer CD (1998) Effects of sex steroids on plasma total homocysteine levels: a study in transsexual males and females. J Clin Endocrinol Metab 83(2):550–553. doi:10.1210/jcem.83.2.4574

    Article  CAS  PubMed  Google Scholar 

  29. Mijatovic V, Kenemans P, Jakobs C, van Baal WM, Peters-Muller ER, van der Mooren MJ (1998) A randomized controlled study of the effects of 17beta-estradiol-dydrogesterone on plasma homocysteine in postmenopausal women. Obstet Gynecol 91(3):432–436

    Article  CAS  PubMed  Google Scholar 

  30. de Bree A, Verschuren WM, Blom HJ, Kromhout D (2001) Lifestyle factors and plasma homocysteine concentrations in a general population sample. Am J Epidemiol 154(2):150–154

    Article  PubMed  Google Scholar 

  31. Shmeleva VM, Kapustin SI, Papayan LP, Sobczynska-Malefora A, Harrington DJ, Savidge GF (2003) Prevalence of hyperhomocysteinemia and the MTHFR C677T polymorphism in patients with arterial and venous thrombosis from North Western Russia. Thromb Res 111(6):351–356

    Article  CAS  PubMed  Google Scholar 

  32. Vermaak WJ, Ubbink JB, Barnard HC, Potgieter GM, van Jaarsveld H, Groenewald AJ (1990) Vitamin B-6 nutrition status and cigarette smoking. Am J Clin Nutr 51(6):1058–1061

    CAS  PubMed  Google Scholar 

  33. Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, Andria G, Boers GH, Bromberg IL, Cerone R et al (1985) The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 37(1):1–31

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Kraus JP (1998) Biochemistry and molecular genetics of cystathionine beta-synthase deficiency. Eur J Pediatr 157(Suppl 2):S50–S53

    Article  CAS  PubMed  Google Scholar 

  35. Ogier de Baulny H, Gerard M, Saudubray JM, Zittoun J (1998) Remethylation defects: guidelines for clinical diagnosis and treatment. Eur J Pediatr 157(Suppl 2):S77–S83

    Article  PubMed  Google Scholar 

  36. Kang SS, Zhou J, Wong PW, Kowalisyn J, Strokosch G (1988) Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 43(4):414–421

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113. doi:10.1038/ng0595-111

    Article  CAS  PubMed  Google Scholar 

  38. Kang SS, Wong PW, Norusis M (1987) Homocysteinemia due to folate deficiency. Metab Clin Exp 36(5):458–462

    Article  CAS  PubMed  Google Scholar 

  39. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270(22):2693–2698

    Article  CAS  PubMed  Google Scholar 

  40. Bostom AG, Lathrop L (1997) Hyperhomocysteinemia in end-stage renal disease: prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int 52(1):10–20

    Article  CAS  PubMed  Google Scholar 

  41. Robertson J, Iemolo F, Stabler SP, Allen RH, Spence JD (2005) Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products. Can Med Assoc J = journal de l'Association medicale canadienne 172(12):1569–1573. doi:10.1503/cmaj.045055

    Article  Google Scholar 

  42. Sengwayo D, Moraba M, Motaung S (2013) Association of homocysteinaemia with hyperglycaemia, dyslipidaemia, hypertension and obesity. Cardiovasc J Afr 24(7):265–269. doi:10.5830/CVJA-2013-059

    Article  PubMed  PubMed Central  Google Scholar 

  43. Derouiche F, Bole-Feysot C, Naimi D, Coeffier M (2014) Hyperhomocysteinemia-induced oxidative stress differentially alters proteasome composition and activities in heart and aorta. Biochem Biophys Res Commun 452(3):740–745. doi:10.1016/j.bbrc.2014.08.141

    Article  CAS  PubMed  Google Scholar 

  44. Lai WK, Kan MY (2015) Homocysteine-Induced Endothelial Dysfunction. Ann Nutr Metab 67(1):1–12. doi:10.1159/000437098

    Article  CAS  PubMed  Google Scholar 

  45. Lussana F, Betti S, D'Angelo A, De Stefano V, Fedi S, Ferrazzi P, Legnani C, Marcucci R, Palareti G, Rota LL, Sampietro F, Squizzato A, Prisco D, Cattaneo M (2013) Evaluation of the prevalence of severe hyperhomocysteinemia in adult patients with thrombosis who underwent screening for thrombophilia. Thromb Res 132(6):681–684. doi:10.1016/j.thromres.2013.09.038

    Article  CAS  PubMed  Google Scholar 

  46. Splaver A, Lamas GA, Hennekens CH (2004) Homocysteine and cardiovascular disease: biological mechanisms, observational epidemiology, and the need for randomized trials. Am Heart J 148(1):34–40. doi:10.1016/j.ahj.2004.02.004

    Article  CAS  PubMed  Google Scholar 

  47. Karatela RA, Sainani GS (2009) Plasma homocysteine in obese, overweight and normal weight hypertensives and normotensives. Indian Heart J 61(2):156–159

    PubMed  Google Scholar 

  48. Li Z, Guo X, Chen S, Zheng L, Yang H, Sun G, Yu S, Li W, Zhou L, Wang J, Hu W, Sun Y (2015) Hyperhomocysteinemia independently associated with the risk of hypertension: a cross-sectional study from rural China. J Hum Hypertens. doi:10.1038/jhh.2015.75

  49. Lim U, Cassano PA (2002) Homocysteine and blood pressure in the third National Health and nutrition examination survey, 1988-1994. Am J Epidemiol 156(12):1105–1113

    Article  PubMed  Google Scholar 

  50. Sen U, Tyagi SC (2010) Homocysteine and hypertension in diabetes: does PPARgamma have a regulatory role? PPAR Res 2010:806538. doi:10.1155/2010/806538

    Article  PubMed  PubMed Central  Google Scholar 

  51. Stehouwer CD, van Guldener C (2003) Does homocysteine cause hypertension? Clin Chem Lab Med 41(11):1408–1411. doi:10.1515/CCLM.2003.216

    Article  CAS  PubMed  Google Scholar 

  52. Tsai JC, Kuo HT, Chiu YW, Hwang SJ, Chuang HY, Chang JM, Chen HC, Lai YH (2005) Correlation of plasma homocysteine level with arterial stiffness and pulse pressure in hemodialysis patients. Atherosclerosis 182(1):121–127. doi:10.1016/j.atherosclerosis.2005.01.038

    Article  CAS  PubMed  Google Scholar 

  53. White WM, Turner ST, Bailey KR, Mosley TH Jr, Kardia SL, Wiste HJ, Kullo IJ, Garovic VD (2013) Hypertension in pregnancy is associated with elevated homocysteine levels later in life. Am J Obstet Gynecol 209(5):454 e451–454 e457. doi:10.1016/j.ajog.2013.06.030

    Article  Google Scholar 

  54. Itani HA, Harrison DG (2015) Memories that last in hypertension. Am J Physiol Renal Physiol 308(11):F1197–F1199. doi:10.1152/ajprenal.00633.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. McCarthy CG, Goulopoulou S, Wenceslau CF, Spitler K, Matsumoto T, Webb RC (2014) Toll-like receptors and damage-associated molecular patterns: novel links between inflammation and hypertension. Am J Phys Heart Circ Phys 306(2):H184–H196. doi:10.1152/ajpheart.00328.2013

    CAS  Google Scholar 

  56. Shirai T, Hilhorst M, Harrison DG, Goronzy JJ, Weyand CM (2015) Macrophages in vascular inflammation--from atherosclerosis to vasculitis. Autoimmunity 48(3):139–151. doi:10.3109/08916934.2015.1027815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhang D, Fang P, Jiang X, Nelson J, Moore JK, Kruger WD, Berretta RM, Houser SR, Yang X, Wang H (2012) Severe hyperhomocysteinemia promotes bone marrow-derived and resident inflammatory monocyte differentiation and atherosclerosis in LDLr/CBS-deficient mice. Circ Res 111(1):37–49. doi:10.1161/CIRCRESAHA.112.269472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Feener EP, King GL (1997) Vascular dysfunction in diabetes mellitus. Lancet 350(Suppl 1):SI9–S13

    Article  PubMed  Google Scholar 

  59. Schaper W, Buschmann I (1999) Collateral circulation and diabetes. Circulation 99(17):2224–2226

    Article  CAS  PubMed  Google Scholar 

  60. Waltenberger J, Lange J, Kranz A (2000) Vascular endothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: a potential predictor for the individual capacity to develop collaterals. Circulation 102(2):185–190

    Article  CAS  PubMed  Google Scholar 

  61. Hirschi KK, Ingram DA, Yoder MC (2008) Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 28(9):1584–1595. doi:10.1161/ATVBAHA.107.155960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Caballero S, Sengupta N, Afzal A, Chang KH, Li Calzi S, Guberski DL, Kern TS, Grant MB (2007) Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells. Diabetes 56(4):960–967. doi:10.2337/db06-1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M, Grego F, Vigili de Kreutzenberg S, Tiengo A, Agostini C, Avogaro A (2006) Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol 26(9):2140–2146. doi:10.1161/01.ATV.0000237750.44469.88

    Article  CAS  PubMed  Google Scholar 

  64. Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, Levine JP, Gurtner GC (2002) Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106(22):2781–2786

    Article  PubMed  Google Scholar 

  65. Catrina SB, Okamoto K, Pereira T, Brismar K, Poellinger L (2004) Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function. Diabetes 53(12):3226–3232

    Article  CAS  PubMed  Google Scholar 

  66. Liu Q, Liang Y, Zou P, Ni WX, Li YG, Chen SM (2013) Hypoxia-inducible factor-1alpha polymorphisms link to coronary artery collateral development and clinical presentation of coronary artery disease. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 157(4):340–345. doi:10.5507/bp.2013.061

    CAS  PubMed  Google Scholar 

  67. Yamada N, Horikawa Y, Oda N, Iizuka K, Shihara N, Kishi S, Takeda J (2005) Genetic variation in the hypoxia-inducible factor-1alpha gene is associated with type 2 diabetes in Japanese. J Clin Endocrinol Metab 90(10):5841–5847. doi:10.1210/jc.2005-0991

    Article  CAS  PubMed  Google Scholar 

  68. Chou E, Suzuma I, Way KJ, Opland D, Clermont AC, Naruse K, Suzuma K, Bowling NL, Vlahos CJ, Aiello LP, King GL (2002) Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic states: a possible explanation for impaired collateral formation in cardiac tissue. Circulation 105(3):373–379

    Article  CAS  PubMed  Google Scholar 

  69. Rivard A, Silver M, Chen D, Kearney M, Magner M, Annex B, Peters K, Isner JM (1999) Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol 154(2):355–363. doi:10.1016/S0002-9440(10)65282-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics Health Sciences Building, University of Louisville, Louisville, KY, USA

    Pankaj Chaturvedi Ph.D

Authors
  1. Pankaj Chaturvedi Ph.D
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pankaj Chaturvedi Ph.D .

Editor information

Editors and Affiliations

  1. Division of Cardiovascular Diseases and Diabetes Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India

    C.C. Kartha

  2. Division of Cardiovascular Diseases and Diabetes Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India

    Surya Ramachandran

  3. Translational Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India

    Radhakrishna M. Pillai

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Chaturvedi, P. (2017). Vascular Remodeling: Homocysteine and Diabetes. In: Kartha, C., Ramachandran, S., Pillai, R. (eds) Mechanisms of Vascular Defects in Diabetes Mellitus. Advances in Biochemistry in Health and Disease, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-319-60324-7_21

Download citation

Publish with us

Policies and ethics

Search

Navigation