Skip to main content
SpringerLink
Log in

Restoration of Angiogenesis: A Promising Therapeutic Strategy in Diabetic Cardiomyopathy

  • Chapter
  • First Online:
Diabetic Cardiomyopathy

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 9))

  • 7252 Accesses

Abstract

Diabetic cardiomyopathy involves vascular endothelial cell dysfunction with structural abnormalities related to hyperglycemia and insulin resistance leading to cardiac complications. The cardiac disorder in diabetic condition is characterized by alteration in myocardial vascular endothelial growth factor (VEGF) and VEGF receptor expression levels, which are well-known regulators of angiogenesis. Hence, promoting angiogenesis in heart can be of therapeutic importance to increase blood flow and reduce vasoconstriction to prevent tissue ischemia and myocyte necrosis. Apart from VEGF, fibroblast growth factor, platelet-derived growth factor, hepatocyte growth factor, and placental growth factor may be involved in defective intracellular signaling in diabetes. Therefore, targeting disturbed intracellular signaling with various strategies to restore angiogenesis using small molecules may be a promising strategy in the management of diabetic cardiomyopathy.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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. Kolluru G, Bir SC, Kevil CG (2012) Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med. doi:10.1155/2012/918267

    PubMed Central  PubMed  Google Scholar 

  2. Calcutt NA, Cooper ME, Kern TS et al (2009) Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials. Nat Rev Drug Discov 8:417–429

    Article  CAS  PubMed  Google Scholar 

  3. Baliga V, Sapsford R (2009) Diabetes mellitus and heart failure: an overview of epidemiology and management. Diab Vasc Dis Res 6:164–171

    Article  CAS  PubMed  Google Scholar 

  4. Han B, Baliga R, Huang H et al (2009) Decreased cardiac expression of vascular endothelial growth factor and redox imbalance in murine diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol 297:H829–H835

    Article  CAS  PubMed  Google Scholar 

  5. Acar E, Ural D, Bildirici U et al (2011) Diabetic cardiomyopathy. Anadolu Kardiyol Derg 11:732–737

    PubMed  Google Scholar 

  6. Hayat S, Patel B, Khattar R et al (2004) Diabetic cardiomyopathy: mechanisms, diagnosis and treatment. Clin Sci 107:539–557

    Article  CAS  PubMed  Google Scholar 

  7. Abel ED (2005) Myocardial insulin resistance and cardiac complications of diabetes. Curr Drug Targets Immune Endocr Metabol Disord 5:219–226

    Article  CAS  PubMed  Google Scholar 

  8. Pacher P, Szabo C (2006) Role of peroxynitrite in the pathogenesis of cardiovascular complications of diabetes. Curr Opin Pharmacol 6:136–141

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. He Z, Rask-Madsen C, King GL (2003) Managing heart disease: mechanisms of cardiovascular complications in diabetes and potential new pharmacological therapies. Eur Heart J 5:B51–B57

    Article  CAS  Google Scholar 

  10. Miki T, Yuda S, Kouzu H et al (2012) Diabetic cardiomyopathy: pathophysiology and clinical features. Heart Fail Rev. doi:10.1007/s10741-012-9313-3

    PubMed Central  Google Scholar 

  11. Liu H, Yu S, Zhang H et al (2012) Angiogenesis impairment in diabetes: role of methylglyoxal-induced receptor for advanced glycation end products, autophagy and vascular endothelial growth factor receptor 2. PLoS One. doi:10.1371/journal.pone.0046720

    Google Scholar 

  12. Farhangkhoee H, Khan Z, Kaur H et al (2006) Vascular endothelial dysfunction in diabetic cardiomyopathy: pathogenesis and potential treatment targets. Pharmacol Ther 111:384–399

    Article  CAS  PubMed  Google Scholar 

  13. Voulgari C, Papadogiannis D, Tentolouris N (2010) Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies. Vasc Health Risk Manag 6:883–903

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Schaffer S, Jong C, Mozaffari M (2012) Role of oxidative stress in diabetes-mediated vascular dysfunction: unifying hypothesis of diabetes revisited. Vascul Pharmacol 57:139–149

    Article  CAS  PubMed  Google Scholar 

  15. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Roe N, Ren J (2012) Nitric oxide synthase uncoupling: a therapeutic target in cardiovascular diseases. Vascul Pharmacol 57:168–172

    Article  CAS  PubMed  Google Scholar 

  17. Simons M (2005) Angiogenesis, arteriogenesis, and diabetes paradigm reassessed? J Am Coll Cardiol 46:835–837

    Article  PubMed  Google Scholar 

  18. Xu J, Zhou Q, Xu W et al (2012) Endoplasmic reticulum stress and diabetic cardiomyopathy. Exp Diabetes Res. doi:10.1155/2012/827971

    Google Scholar 

  19. Lu J, Yao Y, Dai Q et al (2012) Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats. Cardiovasc Diabetol. doi:10.1186/1475-2840-11-105

    Google Scholar 

  20. Sasso F, Torella D, Carbonara O et al (2005) Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease. Diabetes paradigm reassessed? J Am Coll Cardiol 46:827–834

    Article  CAS  PubMed  Google Scholar 

  21. Xu L, Kanasaki K, Kitada M et al (2012) Diabetic angiopathy and angiogenic defects. Fibrogenesis Tissue Repair. doi:10.1186/1755-1536-5-13

    Google Scholar 

  22. Shiojima I, Walsh K (2006) Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes Dev 20:3347–3365

    Article  CAS  PubMed  Google Scholar 

  23. Chou E, Suzuma I, Way K et al (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 105:373–379

    Article  CAS  PubMed  Google Scholar 

  24. Khazaei M, Fallahzadeh A, Sharifi M et al (2011) Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats. Clinics 66:1419–1424

    Article  PubMed Central  PubMed  Google Scholar 

  25. Laham R, Chronos N, Pike M et al (2000) Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a phase I open-label dose escalation study. J Am Coll Cardiol 36:2132–2139

    Article  CAS  PubMed  Google Scholar 

  26. Boodhwani M, Sellke F (2009) Therapeutic angiogenesis in diabetes and hypercholesterolemia: influence of oxidative stress. Antioxid Redox Signal 11:1945–1959

    Article  CAS  PubMed  Google Scholar 

  27. Chachques J, Duarte F, Herreros J et al (2003) Cellular myogenic and angiogenic therapy for patients with cardiac or limb ischemia. Basic Appl Myol 13:29–37

    Google Scholar 

  28. Park H, Yang F, Cho S (2012) Nonviral delivery of genetic medicine for therapeutic angiogenesis. Adv Drug Deliv Rev 64:40–52

    Article  CAS  PubMed  Google Scholar 

  29. Kim H, Rhim T, Lee M (2011) Regulatory systems for hypoxia-inducible gene expression in ischemic heart disease gene therapy. Adv Drug Deliv Rev 63:678–687

    Article  CAS  PubMed  Google Scholar 

  30. Yoon Y, Uchida S, Masuo O et al (2005) Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor. Circulation 111:2073–2085

    Article  CAS  PubMed  Google Scholar 

  31. Gonzalez A, Ravassa S, Beaumont J et al (2011) New targets to treat the structural remodeling of the myocardium. J Am Coll Cardiol 58:1833–1843

    Article  CAS  PubMed  Google Scholar 

  32. Lim Y, Joe J, Jang K et al (2011) Effects of granulocyte-colony stimulating factor (G-CSF) on diabetic cardiomyopathy in Otsuka Long-Evans Tokushima fatty rats. Cardiovasc Diabetol. doi:10.1186/1475-2840-10-92

    PubMed Central  PubMed  Google Scholar 

  33. Krzeminski T, Nozynski J, Grzyb J et al (2005) Angiogenesis and cardioprotection after TNFβ-inducer-Tolpa peat preparation treatment in rat hearts after experimental myocardial infarction in vivo. Vascul Pharmacol 43:164–170

    Article  CAS  PubMed  Google Scholar 

  34. Khurana R, Simons M, Martin J et al (2005) Role of angiogenesis in cardiovascular disease: a critical appraisal. Circulation 112:1813–1824

    Article  PubMed  Google Scholar 

  35. Beohar N, Rapp J, Pandya S et al (2010) Rebuilding the damaged heart—the potential of cytokines and growth factors in the treatment of ischemic heart disease. J Am Coll Cardiol 56:1287–1297

    Article  PubMed Central  PubMed  Google Scholar 

  36. Arom K, Ruengsakulrach P, Belkin M et al (2009) Intramyocardial angiogenic cell precursors in nonischemic dilated cardiomyopathy. Asian Cardiovasc Thorac Ann 17:382–388

    Article  PubMed  Google Scholar 

  37. Riou B (2008) Diabetic cardiomyopathy and anesthesia. Anesthesiology 108:524–530

    Article  Google Scholar 

  38. Robich M, Osipov R, Chu L et al (2011) Resveratrol modifies risk factors for coronary artery disease in swine with metabolic syndrome and myocardial ischemia. Eur J Pharmacol 664:45–53

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Park C, Kim H, Lim J et al (2009) Vascular endothelial growth factor inhibition by dRK6 causes endothelial apoptosis, fibrosis, and inflammation in the heart via the Akt/eNOS axis in db/db mice. Diabetes 58:2666–2676

    Article  CAS  PubMed  Google Scholar 

  40. Ozawa T, Oda H, Oda M et al (2009) Improved cardiac function after sirolimus-eluting stent placement in diabetic patients by pioglitazone: combination therapy with statin. J Cardiol 53:402–409

    Article  PubMed  Google Scholar 

  41. Yu W, Wu J, Cai F et al (2012) Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PLoS One. doi:10.1371/journal.pone.0052013

    Google Scholar 

  42. Tobin J, Celeste A (2006) Bone morphogenetic proteins and growth differentiation factors as drug targets in cardiovascular and metabolic diseases. Drug Discov Today 11:405–411

    Article  CAS  PubMed  Google Scholar 

  43. Gurusamya N, Watanabea K, Maa M et al (2006) Glycogen synthase kinase 3b together with 14-3-3 protein regulates diabetic cardiomyopathy: effect of losartan and tempol. FEBS Lett 580:1932–1940

    Article  Google Scholar 

  44. Rodriguez-Pascuala F, Busnadiego O, Lagares D et al (2011) Role of endothelin in the cardiovascular system. Pharmacol Res 63:463–472

    Article  Google Scholar 

  45. Ergul A (2011) Endothelin-1 and diabetic complications: focus on the vasculature. Pharmacol Res 63:477–482

    Article  CAS  PubMed  Google Scholar 

  46. Ong S, Hausenloy D (2012) Hypoxia-inducible factor as a therapeutic target for cardioprotection. Pharmacol Ther 136:69–81

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, SPP School of Pharmacy and Technology Management, SVKM’s NMIMS, V. L. Mehta Road, Mumbai, Maharashtra, 400056, India

    Veeranjaneyulu Addepalli

  2. Departments of Pharmaceutical Analysis, SPP School of Pharmacy and Technology Management, SVKM’s NMIMS, V. L. Mehta Road, Mumbai, Maharashtra, 400056, India

    Dipti Gatne

Authors
  1. Veeranjaneyulu Addepalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dipti Gatne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Veeranjaneyulu Addepalli .

Editor information

Editors and Affiliations

  1. Department of Biophysics, University of Ankara, Ankara, Ankara, Turkey

    Belma Turan

  2. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Addepalli, V., Gatne, D. (2014). Restoration of Angiogenesis: A Promising Therapeutic Strategy in Diabetic Cardiomyopathy. In: Turan, B., Dhalla, N. (eds) Diabetic Cardiomyopathy. Advances in Biochemistry in Health and Disease, vol 9. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9317-4_21

Download citation

Publish with us

Policies and ethics

Search

Navigation