Diabetes Metab J.  2021 Mar;45(2):129-145. 10.4093/dmj.2020.0285.

Application of Animal Models in Diabetic Cardiomyopathy

Affiliations
  • 1Division of Cardiology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
  • 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea

Abstract

Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.

Keyword

Cardiomyopathies; Diabetes mellitus; Disease models, animal; Heart failure

Figure

  • Fig. 1. Pathological and functional changes of diabetic cardiomyopathy. The pathologies of the diabetic hearts show that the increases in reactive oxygen species generation, apoptosis, cardiac hypertrophy, mitochondrial dysfunction, and myocardial fibrosis than non-diabetic heart. Diabetes mellitus (vs. no diabetes mellitus) is also associated with heart failure with preserved ejection fraction characterized by reduced compliance (reduced mitral E/A ratio) and diastolic dysfunction. ROS, reactive oxygen species; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; RV, right ventricle; LV, left ventricle.


Cited by  1 articles

Evaluation and Management of Patients with Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
Kyu-Sun Lee, Junghyun Noh, Seong-Mi Park, Kyung Mook Choi, Seok-Min Kang, Kyu-Chang Won, Hyun-Jai Cho, Min Kyong Moon
Diabetes Metab J. 2023;47(1):10-26.    doi: 10.4093/dmj.2022.0420.


Reference

1. Tate M, Prakoso D, Willis AM, Peng C, Deo M, Qin CX, et al. Characterising an alternative murine model of diabetic cardiomyopathy. Front Physiol. 2019; 10:1395.
Article
2. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF diabetes atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017; 128:40–50.
Article
3. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR; UKPDS Study Group. Risk factors for renal dysfunction in type 2 diabetes: U.K. prospective diabetes study 74. Diabetes. 2006; 55:1832–9.
Article
4. Semeraro F, Cancarini A, dell’Omo R, Rezzola S, Romano MR, Costagliola C. Diabetic retinopathy: vascular and inflammatory disease. J Diabetes Res. 2015; 2015:582060.
Article
5. Lee WS, Kim J. Diabetic cardiomyopathy: where we are and where we are going. Korean J Intern Med. 2017; 32:404–21.
Article
6. Maisch B, Alter P, Pankuweit S. Diabetic cardiomyopathy: fact or fiction? Herz. 2011; 36:102–15.
7. Lourenco AP, Leite-Moreira AF, Balligand JL, Bauersachs J, Dawson D, de Boer RA, et al. An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology. Eur J Heart Fail. 2018; 20:216–27.
Article
8. Seferovic PM, Petrie MC, Filippatos GS, Anker SD, Rosano G, Bauersachs J, et al. Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018; 20:853–72.
9. Russo I, Frangogiannis NG. Diabetes-associated cardiac fibrosis: cellular effectors, molecular mechanisms and therapeutic opportunities. J Mol Cell Cardiol. 2016; 90:84–93.
Article
10. Tate M, Grieve DJ, Ritchie RH. Are targeted therapies for diabetic cardiomyopathy on the horizon? Clin Sci (Lond). 2017; 131:897–915.
Article
11. Pappachan JM, Varughese GI, Sriraman R, Arunagirinathan G. Diabetic cardiomyopathy: pathophysiology, diagnostic evaluation and management. World J Diabetes. 2013; 4:177–89.
Article
12. Jia G, DeMarco VG, Sowers JR. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nat Rev Endocrinol. 2016; 12:144–53.
Article
13. Tan Y, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence. Nat Rev Cardiol. 2020; 17:585–607.
Article
14. Riehle C, Bauersachs J. Of mice and men: models and mechanisms of diabetic cardiomyopathy. Basic Res Cardiol. 2018; 114:2.
Article
15. Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, et al. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004; 428:493–521.
Article
16. Mouse Genome Sequencing Consortium, Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, et al. Initial sequencing and comparative analysis of the mouse genome. Nature. 2002; 420:520–62.
Article
17. Clee SM, Attie AD. The genetic landscape of type 2 diabetes in mice. Endocr Rev. 2007; 28:48–83.
Article
18. Joost HG, Schurmann A. The genetic basis of obesity-associated type 2 diabetes (diabesity) in polygenic mouse models. Mamm Genome. 2014; 25:401–12.
Article
19. Fang JY, Lin CH, Huang TH, Chuang SY. In vivo rodent models of type 2 diabetes and their usefulness for evaluating flavonoid bioactivity. Nutrients. 2019; 11:530.
Article
20. Dhuria RS, Singh G, Kaur A, Kaur R, Kaur T. Current status and patent prospective of animal models in diabetic research. Adv Biomed Res. 2015; 4:117.
21. Fuentes-Antras J, Picatoste B, Gomez-Hernandez A, Egido J, Tunon J, Lorenzo O. Updating experimental models of diabetic cardiomyopathy. J Diabetes Res. 2015; 2015:656795.
22. Cook SA, Varela-Carver A, Mongillo M, Kleinert C, Khan MT, Leccisotti L, et al. Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction. Eur Heart J. 2010; 31:100–11.
Article
23. Wright JJ, Kim J, Buchanan J, Boudina S, Sena S, Bakirtzi K, et al. Mechanisms for increased myocardial fatty acid utilization following short-term high-fat feeding. Cardiovasc Res. 2009; 82:351–60.
Article
24. Battiprolu PK, Hojayev B, Jiang N, Wang ZV, Luo X, Iglewski M, et al. Metabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in mice. J Clin Invest. 2012; 122:1109–18.
Article
25. Wende AR, Kim J, Holland WL, Wayment BE, O’Neill BT, Tuinei J, et al. Glucose transporter 4-deficient hearts develop maladaptive hypertrophy in response to physiological or pathological stresses. Am J Physiol Heart Circ Physiol. 2017; 313:H1098–108.
Article
26. Luiken JJ, Koonen DP, Willems J, Zorzano A, Becker C, Fischer Y, et al. Insulin stimulates long-chain fatty acid utilization by rat cardiac myocytes through cellular redistribution of FAT/CD36. Diabetes. 2002; 51:3113–9.
Article
27. Luiken JJ, Coort SL, Willems J, Coumans WA, Bonen A, van der Vusse GJ, et al. Contraction-induced fatty acid translocase/CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling. Diabetes. 2003; 52:1627–34.
Article
28. Glatz JF, Luiken JJ. Dynamic role of the transmembrane glycoprotein CD36 (SR-B2) in cellular fatty acid uptake and utilization. J Lipid Res. 2018; 59:1084–93.
Article
29. Ouwens DM, Diamant M, Fodor M, Habets DD, Pelsers MM, El Hasnaoui M, et al. Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification. Diabetologia. 2007; 50:1938–48.
Article
30. Lee TW, Bai KJ, Lee TI, Chao TF, Kao YH, Chen YJ. PPARs modulate cardiac metabolism and mitochondrial function in diabetes. J Biomed Sci. 2017; 24:5.
Article
31. Du K, Herzig S, Kulkarni RN, Montminy M. TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science. 2003; 300:1574–7.
Article
32. Koh HJ, Toyoda T, Didesch MM, Lee MY, Sleeman MW, Kulkarni RN, et al. Tribbles 3 mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle. Nat Commun. 2013; 4:1871.
Article
33. Gu J, Yan X, Dai X, Wang Y, Lin Q, Xiao J, et al. Metallothionein preserves Akt2 activity and cardiac function via inhibiting TRB3 in diabetic hearts. Diabetes. 2018; 67:507–17.
Article
34. Ti Y, Xie GL, Wang ZH, Bi XL, Ding WY, Wang J, et al. TRB3 gene silencing alleviates diabetic cardiomyopathy in a type 2 diabetic rat model. Diabetes. 2011; 60:2963–74.
Article
35. Mansor LS, Sousa Fialho MD, Yea G, Coumans WA, West JA, Kerr M, et al. Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation. Cardiovasc Res. 2017; 113:737–48.
Article
36. Kim SK, Zhao ZS, Lee YJ, Lee KE, Kang SM, Choi D, et al. Leftventricular diastolic dysfunction may be prevented by chronic treatment with PPAR-alpha or -gamma agonists in a type 2 diabetic animal model. Diabetes Metab Res Rev. 2003; 19:487–93.
37. Forcheron F, Basset A, Abdallah P, Del Carmine P, Gadot N, Beylot M. Diabetic cardiomyopathy: effects of fenofibrate and metformin in an experimental model: the Zucker diabetic rat. Cardiovasc Diabetol. 2009; 8:16.
38. Baraka A, AbdelGawad H. Targeting apoptosis in the heart of streptozotocin-induced diabetic rats. J Cardiovasc Pharmacol Ther. 2010; 15:175–81.
Article
39. Liu J, Liu Y, Chen L, Wang Y, Li J. Glucagon-like peptide-1 analog liraglutide protects against diabetic cardiomyopathy by the inhibition of the endoplasmic reticulum stress pathway. J Diabetes Res. 2013; 2013:630537.
Article
40. Wu L, Wang K, Wang W, Wen Z, Wang P, Liu L, et al. Glucagon-like peptide-1 ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via the PPARα pathway. Aging Cell. 2018; 17:e12763.
Article
41. Ramirez E, Picatoste B, Gonzalez-Bris A, Oteo M, Cruz F, Caro-Vadillo A, et al. Sitagliptin improved glucose assimilation in detriment of fatty-acid utilization in experimental type-II diabetes: role of GLP-1 isoforms in Glut4 receptor trafficking. Cardiovasc Diabetol. 2018; 17:12.
Article
42. Hamdani N, Hervent AS, Vandekerckhove L, Matheeussen V, Demolder M, Baerts L, et al. Left ventricular diastolic dysfunction and myocardial stiffness in diabetic mice is attenuated by inhibition of dipeptidyl peptidase 4. Cardiovasc Res. 2014; 104:423–31.
Article
43. Li N, Zhou H. SGLT2 inhibitors: a novel player in the treatment and prevention of diabetic cardiomyopathy. Drug Des Devel Ther. 2020; 14:4775–88.
44. Hamouda NN, Sydorenko V, Qureshi MA, Alkaabi JM, Oz M, Howarth FC. Dapagliflozin reduces the amplitude of shortening and Ca(2+) transient in ventricular myocytes from streptozotocin-induced diabetic rats. Mol Cell Biochem. 2015; 400:57–68.
Article
45. Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017; 104:298–310.
Article
46. Joubert M, Jagu B, Montaigne D, Marechal X, Tesse A, Ayer A, et al. The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents cardiomyopathy in a diabetic lipodystrophic mouse model. Diabetes. 2017; 66:1030–40.
Article
47. Durak A, Olgar Y, Degirmenci S, Akkus E, Tuncay E, Turan B. A SGLT2 inhibitor dapagliflozin suppresses prolonged ventricular-repolarization through augmentation of mitochondrial function in insulin-resistant metabolic syndrome rats. Cardiovasc Diabetol. 2018; 17:144.
Article
48. Cai L, Kang YJ. Oxidative stress and diabetic cardiomyopathy: a brief review. Cardiovasc Toxicol. 2001; 1:181–93.
Article
49. Wilson AJ, Gill EK, Abudalo RA, Edgar KS, Watson CJ, Grieve DJ. Reactive oxygen species signalling in the diabetic heart: emerging prospect for therapeutic targeting. Heart. 2018; 104:293–9.
Article
50. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000; 404:787–90.
Article
51. Tan Y, Ichikawa T, Li J, Si Q, Yang H, Chen X, et al. Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo. Diabetes. 2011; 60:625–33.
Article
52. Ni R, Cao T, Xiong S, Ma J, Fan GC, Lacefield JC, et al. Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy. Free Radic Biol Med. 2016; 90:12–23.
Article
53. He X, Kan H, Cai L, Ma Q. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. J Mol Cell Cardiol. 2009; 46:47–58.
Article
54. Xin Y, Bai Y, Jiang X, Zhou S, Wang Y, Wintergerst KA, et al. Sulforaphane prevents angiotensin II-induced cardiomyopathy by activation of Nrf2 via stimulating the Akt/GSK-3ß/Fyn pathway. Redox Biol. 2018; 15:405–17.
Article
55. Gu J, Cheng Y, Wu H, Kong L, Wang S, Xu Z, et al. Metallothionein is downstream of Nrf2 and partially mediates sulforaphane prevention of diabetic cardiomyopathy. Diabetes. 2017; 66:529–42.
Article
56. Fahey JW, Talalay P. Antioxidant functions of sulforaphane: a potent inducer of phase II detoxication enzymes. Food Chem Toxicol. 1999; 37:973–9.
Article
57. Bai Y, Cui W, Xin Y, Miao X, Barati MT, Zhang C, et al. Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol. 2013; 57:82–95.
Article
58. Zhang Z, Wang S, Zhou S, Yan X, Wang Y, Chen J, et al. Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway. J Mol Cell Cardiol. 2014; 77:42–52.
Article
59. Xia Z, Kuo KH, Nagareddy PR, Wang F, Guo Z, Guo T, et al. N-acetylcysteine attenuates PKCbeta2 overexpression and myocardial hypertrophy in streptozotocin-induced diabetic rats. Cardiovasc Res. 2007; 73:770–82.
60. Liu C, Lu XZ, Shen MZ, Xing CY, Ma J, Duan YY, et al. N-acetyl cysteine improves the diabetic cardiac function: possible role of fibrosis inhibition. BMC Cardiovasc Disord. 2015; 15:84.
Article
61. Okazaki T, Otani H, Shimazu T, Yoshioka K, Fujita M, Iwasaka T. Ascorbic acid and N-acetyl cysteine prevent uncoupling of nitric oxide synthase and increase tolerance to ischemia/reperfusion injury in diabetic rat heart. Free Radic Res. 2011; 45:1173–83.
Article
62. Su W, Zhang Y, Zhang Q, Xu J, Zhan L, Zhu Q, et al. N-acetylcysteine attenuates myocardial dysfunction and postischemic injury by restoring caveolin-3/eNOS signaling in diabetic rats. Cardiovasc Diabetol. 2016; 15:146.
63. Candido R, Forbes JM, Thomas MC, Thallas V, Dean RG, Burns WC, et al. A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes. Circ Res. 2003; 92:785–92.
Article
64. Singh VP, Le B, Khode R, Baker KM, Kumar R. Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis. Diabetes. 2008; 57:3297–306.
65. Van Linthout S, Seeland U, Riad A, Eckhardt O, Hohl M, Dhayat N, et al. Reduced MMP-2 activity contributes to cardiac fibrosis in experimental diabetic cardiomyopathy. Basic Res Cardiol. 2008; 103:319–27.
Article
66. Wang Y, Sun W, Du B, Miao X, Bai Y, Xin Y, et al. Therapeutic effect of MG-132 on diabetic cardiomyopathy is associated with its suppression of proteasomal activities: roles of Nrf2 and NF-κB. Am J Physiol Heart Circ Physiol. 2013; 304:H567–78.
Article
67. Mizushige K, Yao L, Noma T, Kiyomoto H, Yu Y, Hosomi N, et al. Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model. Circulation. 2000; 101:899–907.
68. Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000; 97:1784–9.
Article
69. Wan A, Rodrigues B. Endothelial cell-cardiomyocyte crosstalk in diabetic cardiomyopathy. Cardiovasc Res. 2016; 111:172–83.
70. Choi SY, Chang HJ, Choi SI, Kim KI, Cho YS, Youn TJ, et al. Long-term exercise training attenuates age-related diastolic dysfunction: association of myocardial collagen cross-linking. J Korean Med Sci. 2009; 24:32–9.
71. Christoffersen C, Bollano E, Lindegaard ML, Bartels ED, Goetze JP, Andersen CB, et al. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology. 2003; 144:3483–90.
Article
72. Semeniuk LM, Kryski AJ, Severson DL. Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice. Am J Physiol Heart Circ Physiol. 2002; 283:H976–82.
73. Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC. Cardiac fibrosis: the fibroblast awakens. Circ Res. 2016; 118:1021–40.
74. Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 2007; 13:952–61.
Article
75. Smith CL, Baek ST, Sung CY, Tallquist MD. Epicardial-derived cell epithelial-to-mesenchymal transition and fate specification require PDGF receptor signaling. Circ Res. 2011; 108:e15–26.
Article
76. Zammit SC, Cox AJ, Gow RM, Zhang Y, Gilbert RE, Krum H, et al. Evaluation and optimization of antifibrotic activity of cinnamoyl anthranilates. Bioorg Med Chem Lett. 2009; 19:7003–6.
Article
77. Zhang Y, Edgley AJ, Cox AJ, Powell AK, Wang B, Kompa AR, et al. FT011, a new anti-fibrotic drug, attenuates fibrosis and chronic heart failure in experimental diabetic cardiomyopathy. Eur J Heart Fail. 2012; 14:549–62.
78. Tan SM, Zhang Y, Wang B, Tan CY, Zammit SC, Williams SJ, et al. FT23, an orally active antifibrotic compound, attenuates structural and functional abnormalities in an experimental model of diabetic cardiomyopathy. Clin Exp Pharmacol Physiol. 2012; 39:650–6.
Article
79. Biernacka A, Cavalera M, Wang J, Russo I, Shinde A, Kong P, et al. Smad3 signaling promotes fibrosis while preserving cardiac and aortic geometry in obese diabetic mice. Circ Heart Fail. 2015; 8:788–98.
80. Bajpai A, Tilley DG. The role of leukocytes in diabetic cardiomyopathy. Front Physiol. 2018; 9:1547.
Article
81. Lin Y, Tang Y, Wang F. The protective effect of HIF-1α in T lymphocytes on cardiac damage in diabetic mice. Ann Clin Lab Sci. 2016; 46:32–43.
82. Laroumanie F, Douin-Echinard V, Pozzo J, Lairez O, Tortosa F, Vinel C, et al. CD4+ T cells promote the transition from hypertrophy to heart failure during chronic pressure overload. Circulation. 2014; 129:2111–24.
83. Nevers T, Salvador AM, Grodecki-Pena A, Knapp A, Velazquez F, Aronovitz M, et al. Left ventricular T-cell recruitment contributes to the pathogenesis of heart failure. Circ Heart Fail. 2015; 8:776–87.
Article
84. Dong B, Qi D, Yang L, Huang Y, Xiao X, Tai N, et al. TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes. Am J Physiol Heart Circ Physiol. 2012; 303:H732–42.
Article
85. Tao A, Song J, Lan T, Xu X, Kvietys P, Kao R, et al. Cardiomyocyte-fibroblast interaction contributes to diabetic cardiomyopathy in mice: role of HMGB1/TLR4/IL-33 axis. Biochim Biophys Acta. 2015; 1852(10 Pt A):2075–85.
Article
86. Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol. 2018; 15:387–407.
Article
87. Gordon JW, Shaw JA, Kirshenbaum LA. Multiple facets of NFκB in the heart: to be or not to NF-κB. Circ Res. 2011; 108:1122–32.
88. He Y, Hara H, Nunez G. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci. 2016; 41:1012–21.
Article
89. Luo B, Li B, Wang W, Liu X, Xia Y, Zhang C, et al. NLRP3 gene silencing ameliorates diabetic cardiomyopathy in a type 2 diabetes rat model. PLoS One. 2014; 9:e104771.
Article
90. Luo B, Li B, Wang W, Liu X, Liu X, Xia Y, et al. Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model. Cardiovasc Drugs Ther. 2014; 28:33–43.
Article
91. Liu ZW, Wang JK, Qiu C, Guan GC, Liu XH, Li SJ, et al. Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway. Acta Pharmacol Sin. 2015; 36:323–33.
Article
92. Guo X, Xue M, Li CJ, Yang W, Wang SS, Ma ZJ, et al. Protective effects of triptolide on TLR4 mediated autoimmune and inflammatory response induced myocardial fibrosis in diabetic cardiomyopathy. J Ethnopharmacol. 2016; 193:333–44.
Article
93. Nunes KP, de Oliveira AA, Szasz T, Biancardi VC, Webb RC. Blockade of toll-like receptor 4 attenuates erectile dysfunction in diabetic rats. J Sex Med. 2018; 15:1235–45.
Article
94. Carbone S, Mauro AG, Prestamburgo A, Halquist MS, Narayan P, Potere N, et al. An orally available NLRP3 inflammasome inhibitor prevents Western diet-induced cardiac dysfunction in mice. J Cardiovasc Pharmacol. 2018; 72:303–7.
Article
95. Gollmer J, Zirlik A, Bugger H. Established and emerging mechanisms of diabetic cardiomyopathy. J Lipid Atheroscler. 2019; 8:26–47.
Article
96. Chowdhry MF, Vohra HA, Galinanes M. Diabetes increases apoptosis and necrosis in both ischemic and nonischemic human myocardium: role of caspases and poly-adenosine diphosphate-ribose polymerase. J Thorac Cardiovasc Surg. 2007; 134:124–31.
Article
97. Bojunga J, Nowak D, Mitrou PS, Hoelzer D, Zeuzem S, Chow KU. Antioxidative treatment prevents activation of death-receptor- and mitochondrion-dependent apoptosis in the hearts of diabetic rats. Diabetologia. 2004; 47:2072–80.
Article
98. He C, Zhu H, Li H, Zou MH, Xie Z. Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes. Diabetes. 2013; 62:1270–81.
99. Yang L, Zhao D, Ren J, Yang J. Endoplasmic reticulum stress and protein quality control in diabetic cardiomyopathy. Biochim Biophys Acta. 2015; 1852:209–18.
Article
100. Shao CH, Rozanski GJ, Patel KP, Bidasee KR. Dyssynchronous (non-uniform) Ca2+ release in myocytes from streptozotocin-induced diabetic rats. J Mol Cell Cardiol. 2007; 42:234–46.
Article
101. Kranstuber AL, Del Rio C, Biesiadecki BJ, Hamlin RL, Ottobre J, Gyorke S, et al. Advanced glycation end product cross-link breaker attenuates diabetes-induced cardiac dysfunction by improving sarcoplasmic reticulum calcium handling. Front Physiol. 2012; 3:292.
Article
102. Lacombe VA, Viatchenko-Karpinski S, Terentyev D, Sridhar A, Emani S, Bonagura JD, et al. Mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes. Am J Physiol Regul Integr Comp Physiol. 2007; 293:R1787–97.
Article
103. Pereira L, Ruiz-Hurtado G, Rueda A, Mercadier JJ, Benitah JP, Gomez AM. Calcium signaling in diabetic cardiomyocytes. Cell Calcium. 2014; 56:372–80.
Article
104. Erickson JR, Pereira L, Wang L, Han G, Ferguson A, Dao K, et al. Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation. Nature. 2013; 502:372–6.
Article
105. Maier LS, Layug B, Karwatowska-Prokopczuk E, Belardinelli L, Lee S, Sander J, et al. RAnoLazIne for the treatment of diastolic heart failure in patients with preserved ejection fraction: the RALI-DHF proof-of-concept study. JACC Heart Fail. 2013; 1:115–22.
106. Kumar R, Yong QC, Thomas CM, Baker KM. Intracardiac intracellular angiotensin system in diabetes. Am J Physiol Regul Integr Comp Physiol. 2012; 302:R510–7.
107. Kurdi M, Booz GW. New take on the role of angiotensin II in cardiac hypertrophy and fibrosis. Hypertension. 2011; 57:1034–8.
Article
108. DeMarco VG, Aroor AR, Sowers JR. The pathophysiology of hypertension in patients with obesity. Nat Rev Endocrinol. 2014; 10:364–76.
Article
109. Thomas CM, Yong QC, Seqqat R, Chandel N, Feldman DL, Baker KM, et al. Direct renin inhibition prevents cardiac dysfunction in a diabetic mouse model: comparison with an angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor. Clin Sci (Lond). 2013; 124:529–41.
Article
110. Machackova J, Liu X, Lukas A, Dhalla NS. Renin-angiotensin blockade attenuates cardiac myofibrillar remodelling in chronic diabetes. Mol Cell Biochem. 2004; 261:271–8.
Article
111. Symeonides P, Koulouris S, Vratsista E, Triantafyllou K, Ioannidis G, Thalassinos N, et al. Both ramipril and telmisartan reverse indices of early diabetic cardiomyopathy: a comparative study. Eur J Echocardiogr. 2007; 8:480–6.
Article
112. Sharma V, McNeill JH. Parallel effects of β-adrenoceptor blockade on cardiac function and fatty acid oxidation in the diabetic heart: confronting the maze. World J Cardiol. 2011; 3:281–302.
Article
113. Song M, Gong G, Burelle Y, Gustafsson AB, Kitsis RN, Matkovich SJ, et al. Interdependence of Parkin-mediated mitophagy and mitochondrial fission in adult mouse hearts. Circ Res. 2015; 117:346–51.
114. Anderson EJ, Kypson AP, Rodriguez E, Anderson CA, Lehr EJ, Neufer PD. Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart. J Am Coll Cardiol. 2009; 54:1891–8.
115. Montaigne D, Marechal X, Coisne A, Debry N, Modine T, Fayad G, et al. Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients. Circulation. 2014; 130:554–64.
Article
116. Croston TL, Thapa D, Holden AA, Tveter KJ, Lewis SE, Shepherd DL, et al. Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart. Am J Physiol Heart Circ Physiol. 2014; 307:H54–65.
Article
117. Kuo TH, Giacomelli F, Wiener J. Oxidative metabolism of Polytron versus Nagarse mitochondria in hearts of genetically diabetic mice. Biochim Biophys Acta. 1985; 806:9–15.
Article
118. Bugger H, Abel ED. Rodent models of diabetic cardiomyopathy. Dis Model Mech. 2009; 2:454–66.
Article
119. Ghosh S, Pulinilkunnil T, Yuen G, Kewalramani G, An D, Qi D, et al. Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion. Am J Physiol Heart Circ Physiol. 2005; 289:H768–76.
120. Song Y, Du Y, Prabhu SD, Epstein PN. Diabetic cardiomyopathy in OVE26 mice shows mitochondrial ROS production and divergence between in vivo and in vitro contractility. Rev Diabet Stud. 2007; 4:159–68.
Article
121. Bugger H, Boudina S, Hu XX, Tuinei J, Zaha VG, Theobald HA, et al. Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3. Diabetes. 2008; 57:2924–32.
Article
122. Boudina S, Sena S, Theobald H, Sheng X, Wright JJ, Hu XX, et al. Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes. 2007; 56:2457–66.
Article
123. Boudina S, Sena S, O’Neill BT, Tathireddy P, Young ME, Abel ED. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation. 2005; 112:2686–95.
Article
124. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation. 2007; 115:3213–23.
Article
125. Vazquez-Medina JP, Popovich I, Thorwald MA, Viscarra JA, Rodriguez R, Sonanez-Organis JG, et al. Angiotensin receptor-mediated oxidative stress is associated with impaired cardiac redox signaling and mitochondrial function in insulinresistant rats. Am J Physiol Heart Circ Physiol. 2013; 305:H599–607.
126. Vincent HK, Powers SK, Dirks AJ, Scarpace PJ. Mechanism for obesity-induced increase in myocardial lipid peroxidation. Int J Obes Relat Metab Disord. 2001; 25:378–88.
Article
127. Santos DL, Palmeira CM, Seica R, Dias J, Mesquita J, Moreno AJ, et al. Diabetes and mitochondrial oxidative stress: a study using heart mitochondria from the diabetic Goto-Kakizaki rat. Mol Cell Biochem. 2003; 246:163–70.
Article
128. Grijalva J, Hicks S, Zhao X, Medikayala S, Kaminski PM, Wolin MS, et al. Exercise training enhanced myocardial endothelial nitric oxide synthase (eNOS) function in diabetic GotoKakizaki (GK) rats. Cardiovasc Diabetol. 2008; 7:34.
Article
129. Vazquez EJ, Berthiaume JM, Kamath V, Achike O, Buchanan E, Montano MM, et al. Mitochondrial complex I defect and increased fatty acid oxidation enhance protein lysine acetylation in the diabetic heart. Cardiovasc Res. 2015; 107:453–65.
130. Sultana MR, Bagul PK, Katare PB, Anwar Mohammed S, Padiya R, Banerjee SK. Garlic activates SIRT-3 to prevent cardiac oxidative stress and mitochondrial dysfunction in diabetes. Life Sci. 2016; 164:42–51.
Article
131. Chen JF, Murchison EP, Tang R, Callis TE, Tatsuguchi M, Deng Z, et al. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc Natl Acad Sci U S A. 2008; 105:2111–6.
Article
132. Costantino S, Paneni F, Luscher TF, Cosentino F. MicroRNA profiling unveils hyperglycaemic memory in the diabetic heart. Eur Heart J. 2016; 37:572–6.
Article
133. Katare R, Caporali A, Zentilin L, Avolio E, Sala-Newby G, Oikawa A, et al. Intravenous gene therapy with PIM-1 via a cardiotropic viral vector halts the progression of diabetic cardiomyopathy through promotion of prosurvival signaling. Circ Res. 2011; 108:1238–51.
134. Liu X, Liu S. Role of microRNAs in the pathogenesis of diabetic cardiomyopathy. Biomed Rep. 2017; 6:140–5.
Article
135. Zheng D, Ma J, Yu Y, Li M, Ni R, Wang G, et al. Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice. Diabetologia. 2015; 58:1949–58.
Article
136. Raut SK, Kumar A, Singh GB, Nahar U, Sharma V, Mittal A, et al. miR-30c mediates upregulation of Cdc42 and Pak1 in diabetic cardiomyopathy. Cardiovasc Ther. 2015; 33:89–97.
Article
137. Li X, Du N, Zhang Q, Li J, Chen X, Liu X, et al. MicroRNA30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy. Cell Death Dis. 2014; 5:e1479.
Article
138. Yoon S, Eom GH. Heart failure with preserved ejection fraction: present status and future directions. Exp Mol Med. 2019; 51:1–9.
Article
139. Borlaug BA. The pathophysiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2014; 11:507–15.
Article
140. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC): developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016; 18:891–975.
141. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Failure Society of America. Circulation. 2017; 136:e137–61.
142. Shah SJ, Katz DH, Selvaraj S, Burke MA, Yancy CW, Gheorghiade M, et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015; 131:269–79.
Article
143. Valero-Munoz M, Backman W, Sam F. Murine models of heart failure with preserved ejection fraction: a “fishing expedition”. JACC Basic Transl Sci. 2017; 2:770–89.
144. Zhang L, Li Q, Wolff LT, Antonio GE, Yeung DK, Zhang A, et al. Changes of brain activity in the aged SAMP mouse. Biogerontology. 2007; 8:81–8.
Article
145. Grobe JL, Buehrer BA, Hilzendeger AM, Liu X, Davis DR, Xu D, et al. Angiotensinergic signaling in the brain mediates metabolic effects of deoxycorticosterone (DOCA)-salt in C57 mice. Hypertension. 2011; 57:600–7.
Article
146. Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail. 2012; 5:720–6.
Article
147. Tanaka K, Wilson RM, Essick EE, Duffen JL, Scherer PE, Ouchi N, et al. Effects of adiponectin on calcium-handling proteins in heart failure with preserved ejection fraction. Circ Heart Fail. 2014; 7:976–85.
Article
148. Mohammed SF, Ohtani T, Korinek J, Lam CS, Larsen K, Simari RD, et al. Mineralocorticoid accelerates transition to heart failure with preserved ejection fraction via “nongenomic effects”. Circulation. 2010; 122:370–8.
Article
149. Matsumura Y, Kuro T, Konishi F, Takaoka M, Gariepy CE, Yanagisawa M. Enhanced blood pressure sensitivity to DOCA-salt treatment in endothelin ET(B) receptor-deficient rats. Br J Pharmacol. 2000; 129:1060–2.
Article
150. Ho CY, Lopez B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P, et al. Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. N Engl J Med. 2010; 363:552–63.
Article
151. Hadi AM, Mouchaers KT, Schalij I, Grunberg K, Meijer GA, Vonk-Noordegraaf A, et al. Rapid quantification of myocardial fibrosis: a new macro-based automated analysis. Cell Oncol (Dordr). 2011; 34:343–54.
Article
152. Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol. 2009; 53:1925–32.
153. Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell. 1996; 84:491–5.
Article
154. Edvell A, Lindstrom P. Initiation of increased pancreatic islet growth in young normoglycemic mice (Umea +/?). Endocrinology. 1999; 140:778–83.
Article
155. Riehle C, Bauersachs J. Small animal models of heart failure. Cardiovasc Res. 2019; 115:1838–49.
Article
156. Nielsen JM, Kristiansen SB, Norregaard R, Andersen CL, Denner L, Nielsen TT, et al. Blockage of receptor for advanced glycation end products prevents development of cardiac dysfunction in db/db type 2 diabetic mice. Eur J Heart Fail. 2009; 11:638–47.
Article
157. Phillips MS, Liu Q, Hammond HA, Dugan V, Hey PJ, Caskey CJ, et al. Leptin receptor missense mutation in the fatty Zucker rat. Nat Genet. 1996; 13:18–9.
Article
158. Clark JB, Palmer CJ, Shaw WN. The diabetic Zucker fatty rat. Proc Soc Exp Biol Med. 1983; 173:68–75.
Article
159. Schiattarella GG, Altamirano F, Tong D, French KM, Villalobos E, Kim SY, et al. Nitrosative stress drives heart failure with preserved ejection fraction. Nature. 2019; 568:351–6.
Article
160. Prakoso D, De Blasio MJ, Qin C, Rosli S, Kiriazis H, Qian H, et al. Phosphoinositide 3-kinase (p110α) gene delivery limits diabetes-induced cardiac NADPH oxidase and cardiomyopathy in a mouse model with established diastolic dysfunction. Clin Sci (Lond). 2017; 131:1345–60.
Article
161. Wanrooy BJ, Kumar KP, Wen SW, Qin CX, Ritchie RH, Wong CH. Distinct contributions of hyperglycemia and high-fat feeding in metabolic syndrome-induced neuroinflammation. J Neuroinflammation. 2018; 15:293.
Article
162. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003; 52:102–10.
163. Yoshioka M, Kayo T, Ikeda T, Koizumi A. A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes. 1997; 46:887–94.
Article
164. Takaya K, Ogawa Y, Isse N, Okazaki T, Satoh N, Masuzaki H, et al. Molecular cloning of rat leptin receptor isoform complementary DNAs: identification of a missense mutation in Zucker fatty (fa/fa) rats. Biochem Biophys Res Commun. 1996; 225:75–83.
165. Gauguier D, Froguel P, Parent V, Bernard C, Bihoreau MT, Portha B, et al. Chromosomal mapping of genetic loci associated with non-insulin dependent diabetes in the GK rat. Nat Genet. 1996; 12:38–43.
Article
166. Shimomura I, Hammer RE, Richardson JA, Ikemoto S, Bashmakov Y, Goldstein JL, et al. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. 1998; 12:3182–94.
Article
167. Finck BN, Han X, Courtois M, Aimond F, Nerbonne JM, Kovacs A, et al. A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content. Proc Natl Acad Sci U S A. 2003; 100:1226–31.
168. Belke DD, Betuing S, Tuttle MJ, Graveleau C, Young ME, Pham M, et al. Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression. J Clin Invest. 2002; 109:629–39.
Article
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