Top

Published in:

01-11-2010

Stem cells in the diabetic infarcted heart

Authors: Carley E. Glass, Pawan K. Singal, Dinender K. Singla

Published in: Heart Failure Reviews | Issue 6/2010

Abstract

Diabetes mellitus is one of the leading causes of death, and the majority of these deaths are associated with cardiovascular diseases. Development and progression of myocardial infarction leading to heart failure is much more complex and multifactorial in diabetics compared with non-diabetics. Despite significant advances in pharmacological interventions and surgical techniques, the disease progression leading to diabetic end-stage heart failure remains very high. Recently, cell therapy has gained much attention as an alternative approach to treat various heart diseases. However, transplanted stem cell studies in diabetic animal models are very limited. In this review, we discuss the pathogenesis of the diabetic infarcted heart and the potential of stem cell therapy to repair and regenerate.

Aronson D, Rayfield EJ, Chesebro JH (1997) Mechanisms determining course and outcome of diabetic patients who have had acute myocardial infarction. Ann Intern Med 126:296–306PubMed

Rahman S, Rahman T, Ismail AA, Rashid AR (2007) Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis. Diabetes Obes Metab 9:767–780CrossRefPubMed

Woodfield SL, Lundergan CF, Reiner JS, Greenhouse SW, Thompson MA, Rohrbeck SC, Deychak Y, Simoons ML, Califf RM, Topol EJ, Ross AM (1996) Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-I experience. J Am Coll Cardiol 28:1661–1669CrossRefPubMed

Singla DK, Hacker TA, Ma L, Douglas PS, Sullivan R, Lyons GE, Kamp TJ (2006) Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types. J Mol Cell Cardiol 40:195–200CrossRefPubMed

Singla DK, Lyons GE, Kamp TJ (2007) Transplanted embryonic stem cells following mouse myocardial infarction inhibit apoptosis and cardiac remodeling. Am J Physiol Heart Circ Physiol 293:H1308–H1314CrossRefPubMed

Min JY, Yang Y, Converso KL, Liu L, Huang Q, Morgan JP, Xiao YF (2002) Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats. J Appl Physiol 92:288–296CrossRefPubMed

Jing D, Parikh A, Canty JM Jr, Tzanakakis ES (2008) Stem cells for heart cell therapies Tissue Eng Part B Rev 14:393–406

Tenerz A, Lonnberg I, Berne C, Nilsson G, Leppert J (2001) Myocardial infarction and prevalence of diabetes mellitus. Is increased casual blood glucose at admission a reliable criterion for the diagnosis of diabetes? Eur Heart J 22:1102–1110CrossRefPubMed

Roger VL, Weston SA, Gerber Y, Killian JM, Dunlay SM, Jaffe AS, Bell MR, Kors J, Yawn BP, Jacobsen SJ (2010) Trends in incidence, severity, and outcome of hospitalized myocardial infarction. Circulation 121:863–869CrossRefPubMed

10.

Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339:229–234CrossRefPubMed

11.

Hu G, Jousilahti P, Qiao Q, Peltonen M, Katoh S, Tuomilehto J (2005) The gender-specific impact of diabetes and myocardial infarction at baseline and during follow-up on mortality from all causes and coronary heart disease. J Am Coll Cardiol 45:1413–1418CrossRefPubMed

12.

Lundberg V, Stegmayr B, Asplund K, Eliasson M, Huhtasaari F (1997) Diabetes as a risk factor for myocardial infarction: population and gender perspectives. J Intern Med 241:485–492CrossRefPubMed

13.

Lee CD, Folsom AR, Pankow JS, Brancati FL (2004) Cardiovascular events in diabetic and nondiabetic adults with or without history of myocardial infarction. Circulation 109:855–860CrossRefPubMed

14.

Mak KH, Topol EJ (2000) Emerging concepts in the management of acute myocardial infarction in patients with diabetes mellitus. J Am Coll Cardiol 35:563–568CrossRefPubMed

15.

Lomuscio A, Castagnone M, Vergani D, Verzoni A, Beltrami A, Ravaglia R, Pozzoni L (1991) Clinical correlation between diabetic and non diabetic patients with myocardial infarction. Acta Cardiol 46:543–554PubMed

16.

Rees DA, Alcolado JC (2005) Animal models of diabetes mellitus. Diabet Med 22:359–370CrossRefPubMed

17.

Nishina PM, Lowe S, Wang J, Paigen B (1994) Characterization of plasma lipids in genetically obese mice: the mutants obese, diabetes, fat, tubby, and lethal yellow. Metabolism 43:549–553CrossRefPubMed

18.

McGaffin KR, Zou B, McTiernan CF, O’Donnell CP (2009) Leptin attenuates cardiac apoptosis after chronic ischaemic injury. Cardiovasc Res 83:313–324CrossRefPubMed

19.

Gundewar S, Calvert JW, Elrod JW, Lefer DJ (2007) Cytoprotective effects of N, N, N-trimethylsphingosine during ischemia- reperfusion injury are lost in the setting of obesity and diabetes. Am J Physiol Heart Circ Physiol 293:H2462–H2471CrossRefPubMed

20.

Srinivasan K, Ramarao P (2007) Animal models in type 2 diabetes research: an overview. Indian J Med Res 125:451–472PubMed

21.

Greer JJ, Ware DP, Lefer DJ (2006) Myocardial infarction and heart failure in the db/db diabetic mouse. Am J Physiol Heart Circ Physiol 290:146–153CrossRef

22.

Iwatsuka H, Shino A, Suzuoki Z (1970) General survey of diabetic features of yellow KK mice. Endocrinol Jpn 17:23–35PubMed

23.

Chandler MP, Morgan EE, McElfresh TA, Kung TA, Rennison JH, Hoit BD, Young ME (2007) Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats. Am J Physiol Heart Circ Physiol 293:H1609–H1616CrossRefPubMed

24.

Cohen AM, Rosenmann E, Rosenthal T (1993) The Cohen diabetic (non-insulin-dependent) hypertensive rat model. Description of the model and pathologic findings. Am J Hypertens 6:989–995PubMed

25.

Weksler-Zangen S, Yagil C, Zangen DH, Ornoy A, Jacob HJ, Yagil Y (2001) The newly inbred cohen diabetic rat: a nonobese normolipidemic genetic model of diet-induced type 2 diabetes expressing sex differences. Diabetes 50:2521–2529CrossRefPubMed

26.

Matsushima S, Kinugawa S, Yokota T, Inoue N, Ohta Y, Hamaguchi S, Tsutsui H (2009) Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes. Am J Physiol Heart Circ Physiol 297:H409–H416CrossRefPubMed

27.

Thakker GD, Frangogiannis NG, Bujak M, Zymek P, Gaubatz JW, Reddy AK, Taffet G, Michael LH, Entman ML, Ballantyne CM (2006) Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction. Am J Physiol Heart Circ Physiol 291:H2504–H2514CrossRefPubMed

28.

Huang JP, Huang SS, Deng JY, Hung LM (2009) Impairment of insulin-stimulated Akt/GLUT4 signaling is associated with cardiac contractile dysfunction and aggravates I/R injury in STZ-diabetic rats. J Biomed Sci 16:77CrossRefPubMed

29.

Song GY, Wu YJ, Yang YJ, Li JJ, Zhang HL, Pei HJ, Zhao ZY, Zeng ZH, Hui RT (2009) The accelerated post-infarction progression of cardiac remodelling is associated with genetic changes in an untreated streptozotocin-induced diabetic rat model. Eur J Heart Fail 11:911–921CrossRefPubMed

30.

Miki T, Miura T, Hotta H, Tanno M, Yano T, Sato T, Terashima Y, Takada A, Ishikawa S, Shimamoto K (2009) Endoplasmic reticulum stress in diabetic hearts abolishes erythropoietin-induced myocardial protection by impairment of phospho-glycogen synthase kinase-3beta-mediated suppression of mitochondrial permeability transition. Diabetes 58:2863–2872CrossRefPubMed

31.

Dixon RA, Davidson SM, Wynne AM, Yellon DM, Smith CC (2009) The cardioprotective actions of leptin are lost in the Zucker obese (fa/fa) rat. J Cardiovasc Pharmacol 53:311–317CrossRefPubMed

32.

Kristiansen SB, Lofgren B, Stottrup NB, Khatir D, Nielsen-Kudsk JE, Nielsen TT, Botker HE, Flyvbjerg A (2004) Ischaemic preconditioning does not protect the heart in obese and lean animal models of type 2 diabetes. Diabetologia 47:1716–1721CrossRefPubMed

33.

Vahtola E, Louhelainen M, Forsten H, Merasto S, Raivio J, Kaheinen P, Kyto V, Tikkanen I, Levijoki J, Mervaala E (2010) Sirtuin1–p53, forkhead box O3a, p38 and post-infarct cardiac remodeling in the spontaneously diabetic Goto-Kakizaki rat. Cardiovasc Diabetol 9:5CrossRefPubMed

34.

Li TS, Takahashi M, Suzuki R, Kobayashi T, Ito H, Mikamo A, Hamano K (2006) Pravastatin improves remodeling and cardiac function after myocardial infarction by an antiinflammatory mechanism rather than by the induction of angiogenesis. Ann Thorac Surg 81:2217–2225CrossRefPubMed

35.

Bonora E (2006) The metabolic syndrome and cardiovascular disease. Ann Med 38:64–80CrossRefPubMed

36.

Durina J, Remkova A (2007) Prothrombotic state in metabolic syndrome. Bratisl Lek Listy 108:279–280PubMed

37.

Tschoepe D, Roesen P (1998) Heart disease in diabetes mellitus: a challenge for early diagnosis and intervention. Exp Clin Endocrinol Diabetes 106:16–24CrossRefPubMed

38.

Rizzo M, Berneis K (2007) Small dense low-density-lipoproteins and the metabolic syndrome. Diabetes Metab Res Rev 23:14–20CrossRefPubMed

39.

Anfossi G, Russo I, Doronzo G, Trovati M (2007) Relevance of the vascular effects of insulin in the rationale of its therapeutical use. Cardiovasc Hematol Disord Drug Targets 7:228–249CrossRefPubMed

40.

Cersosimo E, Defronzo RA (2006) Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev 22:423–436CrossRefPubMed

41.

Steinberg HO, Baron AD (2002) Vascular function insulin resistance and fatty acids. Diabetologia 45:623–634CrossRefPubMed

42.

Zinn A, Felson S, Fisher E, Schwartzbard A (2008) Reassessing the cardiovascular risks and benefits of thiazolidinediones. Clin Cardiol 31:397–403CrossRefPubMed

43.

Palumbo F, Bianchi C, Miccoli R, Del PS (2003) Hyperglycaemia and cardiovascular risk. Acta Diabetol 40(Suppl 2):S362–S369CrossRefPubMed

44.

Chyun DA, Young LH (2006) Diabetes mellitus and cardiovascular disease. Nurs Clin North Am 41:681–685CrossRefPubMed

45.

Bartnik M, Norhammar A, Ryden L (2007) Hyperglycaemia and cardiovascular disease. J Intern Med 262:145–156CrossRefPubMed

46.

Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefPubMed

47.

Basta G, Schmidt AM, De CR (2004) Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res 63:582–592CrossRefPubMed

48.

Ramana KV, Chandra D, Srivastava S, Bhatnagar A, Srivastava SK (2003) Nitric oxide regulates the polyol pathway of glucose metabolism in vascular smooth muscle cells. FASEB J 17:417–425CrossRefPubMed

49.

Bonnefont-Rousselot D (2002) Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care 5:561–568CrossRefPubMed

50.

Jay D, Hitomi H, Griendling KK (2006) Oxidative stress and diabetic cardiovascular complications. Free Radic Biol Med 40:183–192CrossRefPubMed

51.

Clark RJ, McDonough PM, Swanson E, Trost SU, Suzuki M, Fukuda M, Dillmann WH (2003) Diabetes and the accompanying hyperglycemia impairs cardiomyocyte calcium cycling through increased nuclear O-GlcNAcylation. J Biol Chem 278:44230–44237CrossRefPubMed

52.

Federici M, Menghini R, Mauriello A, Hribal ML, Ferrelli F, Lauro D, Sbraccia P, Spagnoli LG, Sesti G, Lauro R (2002) Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells. Circulation 106:466–472CrossRefPubMed

53.

Watanabe K, Thandavarayan RA, Gurusamy N, Zhang S, Muslin AJ, Suzuki K, Tachikawa H, Kodama M, Aizawa Y (2009) Role of 14–3-3 protein and oxidative stress in diabetic cardiomyopathy. Acta Physiol Hung 96:277–287CrossRefPubMed

54.

Peppa M, Stavroulakis P, Raptis SA (2009) Advanced glycoxidation products and impaired diabetic wound healing. Wound Repair Regen 17:461–472CrossRefPubMed

55.

Zheng L, Kern TS (2009) Role of nitric oxide, superoxide, peroxynitrite and PARP in diabetic retinopathy. Front Biosci 14:3974–3987CrossRefPubMed

56.

Madsen-Bouterse SA, Kowluru RA (2008) Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Rev Endocr Metab Disord 9:315–327CrossRefPubMed

57.

Hamada Y, Fujii H, Fukagawa M (2009) Role of oxidative stress in diabetic bone disorder Bone 45(Suppl 1):S35–S38

58.

Potenza MA, Gagliardi S, Nacci C, Carratu’ MR, Montagnani M (2009) Endothelial dysfunction in diabetes: from mechanisms to therapeutic targets. Curr Med Chem 16:94–112CrossRefPubMed

59.

Ha H, Hwang IA, Park JH, Lee HB (2008) Role of reactive oxygen species in the pathogenesis of diabetic nephropathy. Diabetes Res Clin Pract 82(Suppl 1):S42–S45CrossRefPubMed

60.

Figueroa-Romero C, Sadidi M, Feldman EL (2008) Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord 9:301–314CrossRefPubMed

61.

Di FC, Cuzzocrea S, Rossi F, Marfella R, D’Amico M (2006) Oxidative stress as the leading cause of acute myocardial infarction in diabetics. Cardiovasc Drug Rev 24:77–87CrossRef

62.

Misra MK, Sarwat M, Bhakuni P, Tuteja R, Tuteja N (2009) Oxidative stress and ischemic myocardial syndromes. Med Sci Monit 15:RA209–RA219PubMed

63.

Hori M, Nishida K (2009) Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovasc Res 81:457–464CrossRefPubMed

64.

Lopez FA, Casado S (2001) Heart failure, redox alterations and endothelial dysfunction. Hypertension 38:1400–1405CrossRef

65.

Kumar D, Jugdutt BI (2003) Apoptosis and oxidants in the heart. J Lab Clin Med 142:288–297CrossRefPubMed

66.

Kumar D, Lou H, Singal PK (2002) Oxidative stress and apoptosis in heart dysfunction. Herz 27:662–668CrossRefPubMed

67.

Backlund T, Palojoki E, Saraste A, Eriksson A, Finckenberg P, Kyto V, Lakkisto P, Mervaala E, Voipio-Pulkki LM, Laine M, Tikkanen I (2004) Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes. Diabetologia 47:325–330CrossRefPubMed

68.

Melo LG, Pachori AS, Kong D, Gnecchi M, Wang K, Pratt RE, Dzau VJ (2004) Molecular and cell-based therapies for protection, rescue and repair of ischemic myocardium: reasons for cautious optimism. Circulation 109:2386–2393CrossRefPubMed

69.

Cai L, Li W, Wang G, Guo L, Jiang Y, Kang YJ (2002) Hyperglycemia-induced apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated caspase-3 activation pathway. Diabetes 51:1938–1948CrossRefPubMed

70.

Kumar D, Robertson S, Burns KD (2004) Evidence of apoptosis in human diabetic kidney. Mol Cell Biochem 259:67–70CrossRefPubMed

71.

Ejaz S, Chekarova I, Ejaz A, Sohail A, Lim CW (2008) Importance of pericytes and mechanisms of pericyte loss during diabetes retinopathy. Diabetes Obes Metab 10:53–63PubMed

72.

Kamboj SS, Vasishta RK, Sandhir R (2010) N-acetylcysteine inhibits hyperglycemia-induced oxidative stress and apoptosis markers in diabetic neuropathy. J Neurochem 112:77–91CrossRefPubMed

73.

Tuo QH, Zeng H, Stinnett A, Yu H, Aschner JL, Liao DF, Chen JX (2008) Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Am J Physiol Heart Circ Physiol 294:H2547–H2557CrossRefPubMed

74.

Backlund T, Lakkisto P, Palojoki E, Gronholm T, Saraste A, Finckenberg P, Mervaala E, Tikkanen I, Laine M (2007) Activation of protective and damaging components of the cardiac renin-angiotensin system after myocardial infarction in experimental diabetes. J Renin Angiotensin Aldosterone Syst 8:66–73CrossRefPubMed

75.

Swynghedauw B (1999) Molecular mechanisms of myocardial remodeling. Physiol Rev 79:215–262PubMed

76.

Menasche P (2008) Skeletal myoblasts and cardiac repair. J Mol Cell Cardiol 45:545–553CrossRefPubMed

77.

Kim H, Kim SW, Nam D, Kim S, Yoon YS (2009) Cell therapy with bone marrow cells for myocardial regeneration. Antioxid Redox Signal 11:1897–1911CrossRefPubMed

78.

Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y, Terzic A (2009) Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation 120:408–416CrossRefPubMed

79.

Cleland JG, Freemantle N, Coletta AP, Clark AL (2006) Clinical trials update from the American Heart Association: REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE and PROACTIVE. Eur J Heart Fail 8:105–110CrossRefPubMed

80.

Govaert JA, Swijnenburg RJ, Schrepfer S, Xie X, van der Bogt KE, Hoyt G, Stein W, Ransohoff KJ, Robbins RC, Wu JC (2009) Poor functional recovery after transplantation of diabetic bone marrow stem cells in ischemic myocardium. J Heart Lung Transplant 28:1158–1165CrossRefPubMed

81.

Bdel Aziz MT, El-Asmar MF, Haidara M, Atta HM, Roshdy NK, Rashed LA, Sabry D, Youssef MA, Bdel Aziz AT, Moustafa M (2008) Effect of bone marrow-derived mesenchymal stem cells on cardiovascular complications in diabetic rats. Med Sci Monit 14:BR249–BR255

82.

Li JH, Zhang N, Wang JA (2008) Improved anti-apoptotic and anti-remodeling potency of bone marrow mesenchymal stem cells by anoxic pre-conditioning in diabetic cardiomyopathy. J Endocrinol Invest 31:103–110PubMed

83.

Zhang N, Li J, Luo R, Jiang J, Wang JA (2008) Bone marrow mesenchymal stem cells induce angiogenesis and attenuate the remodeling of diabetic cardiomyopathy. Exp Clin Endocrinol Diabetes 116:104–111CrossRefPubMed

Title: Stem cells in the diabetic infarcted heart
Authors: Carley E. Glass
Pawan K. Singal
Dinender K. Singla
Publication date: 01-11-2010
Publisher: Springer US
Published in: Heart Failure Reviews / Issue 6/2010
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-010-9172-8

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Stem cells in the diabetic infarcted heart

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2010

Functional electrical stimulation of lower limbs in patients with chronic heart failure

Role and benefits of exercise in the management of patients with heart failure

Left ventricular non-compaction and its cardiac and neurologic implications

Proinflammatory cytokines in heart failure: double-edged swords

Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms

Granulocyte colony-stimulating factor for ischemic heart failure: should we use it?

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page