REFERENCES
1. International Diabetes Federation. Over 250 million people worldwide unaware they have diabetes, according to new IDF research. 2025. Available from: https://idf.org/news/idf-diabetes-atlas-11th-edition/ [Last accessed on 13 Oct 2025].
2. Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018;17:83.
3. Wang M, Li Y, Li S, Lv J. Endothelial dysfunction and diabetic cardiomyopathy. Front Endocrinol. 2022;13:851941.
4. Salvatore T, Pafundi PC, Galiero R, et al. The diabetic cardiomyopathy: the contributing pathophysiological mechanisms. Front Med. 2021;8:695792.
5. Radzioch E, Dąbek B, Balcerczyk-Lis M, et al. Diabetic cardiomyopathy-from basics through diagnosis to treatment. Biomedicines. 2024;12:765.
6. Jia G, Hill MA, Sowers JR. Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ Res. 2018;122:624-38.
7. 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.
8. Nakamura K, Miyoshi T, Yoshida M, et al. Pathophysiology and treatment of diabetic cardiomyopathy and heart failure in patients with diabetes mellitus. Int J Mol Sci. 2022;23:3587.
9. Shi Y, Vanhoutte PM. Macro- and microvascular endothelial dysfunction in diabetes. J Diabetes. 2017;9:434-49.
10. Yang DR, Wang MY, Zhang CL, Wang Y. Endothelial dysfunction in vascular complications of diabetes: a comprehensive review of mechanisms and implications. Front Endocrinol. 2024;15:1359255.
12. Chilton R, Iranpour EI, Bloomgarden Z. Deciphering the connection: diabetes, pericyte dysfunction, and their impact on cardiovascular health. J Diabetes. 2024;16:e13539.
13. Paik DT, Cho S, Tian L, Chang HY, Wu JC. Single-cell RNA sequencing in cardiovascular development, disease and medicine. Nat Rev Cardiol. 2020;17:457-73.
14. Zhang Y, Cao Y, Zhang X, et al. Single-cell RNA sequencing uncovers pathological processes and crucial targets for vascular endothelial injury in diabetic hearts. Adv Sci. 2024;11:e2405543.
15. Paik DT, Tian L, Williams IM, et al. Single-cell RNA sequencing unveils unique transcriptomic signatures of organ-specific endothelial cells. Circulation. 2020;142:1848-62.
16. Wu L, Islam MR, Lee J, et al. ErbB3 is a critical regulator of cytoskeletal dynamics in brain microvascular endothelial cells: implications for vascular remodeling and blood brain barrier modulation. J Cereb Blood Flow Metab. 2021;41:2242-55.
17. Herbert SP, Stainier DY. Molecular control of endothelial cell behaviour during blood vessel morphogenesis. Nat Rev Mol Cell Biol. 2011;12:551-64.
18. Dejana E. The role of wnt signaling in physiological and pathological angiogenesis. Circ Res. 2010;107:943-52.
19. Kaur N, Guan Y, Raja R, Ruiz-Velasco A, Liu W. Mechanisms and therapeutic prospects of diabetic cardiomyopathy through the inflammatory response. Front Physiol. 2021;12:694864.
20. Bellemare M, Bourcier L, Iglesies-Grau J, Boulet J, O’Meara E, Bouabdallaoui N. Mechanisms of diabetic cardiomyopathy: Focus on inflammation. Diabetes Obes Metab. 2025;27:2326-38.
21. Frati G, Schirone L, Chimenti I, et al. An overview of the inflammatory signalling mechanisms in the myocardium underlying the development of diabetic cardiomyopathy. Cardiovasc Res. 2017;113:378-88.
22. Su Q, Huang W, Huang Y, et al. Single-cell insights: pioneering an integrated atlas of chromatin accessibility and transcriptomic landscapes in diabetic cardiomyopathy. Cardiovasc Diabetol. 2024;23:139.
23. Wen Y, Wang Q. Cardiac endothelial cells and cardiomyocytes alter their communication properties in diabetic mice. Biol Res. 2025;58:23.
24. Li W, Lou X, Zha Y, et al. Single-cell RNA-seq of heart reveals intercellular communication drivers of myocardial fibrosis in diabetic cardiomyopathy. eLife. 2023:12.
25. Song C, Wang S, Fu Z, et al. IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis. Cell Death Dis. 2022;13:340.
26. Chatterjee A, Tumarin J, Prabhakar S. Role of inflammation in the progression of diabetic kidney disease. Vessel Plus. 2024;8:28.
27. Sayed S, Faruq O, Preya UH, Kim JT. Cathepsin S knockdown suppresses endothelial inflammation, angiogenesis, and complement protein activity under hyperglycemic conditions in vitro by inhibiting NF-κB signaling. Int J Mol Sci. 2023;24:5428.
28. Kobayashi S, Zhao F, Kobayashi T, et al. Hyperglycemia-induced cardiomyocyte death is mediated by lysosomal membrane injury and aberrant expression of cathepsin D. Biochem Biophys Res Commun. 2020;523:239-45.
29. Cohen CD, De Blasio MJ, Farrugia GE, et al. Mapping the cellular and molecular landscape of cardiac non-myocytes in murine diabetic cardiomyopathy. iScience. 2023;26:107759.
30. Zygmunciak P, Stróżna K, Błażowska O, Mrozikiewicz-Rakowska B. Extracellular vesicles in diabetic cardiomyopathy-state of the art and future perspectives. Int J Mol Sci. 2024;25:6117.
31. Guo W, Yang C, Zou J, et al. Interleukin-1β polarization in M1 macrophage mediates myocardial fibrosis in diabetes. Int Immunopharmacol. 2024;131:111858.
32. Li C, Meng X, Wang L, Dai X. Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-β/Smad signaling pathway. Front Pharmacol. 2023;14:1092148.
33. Rossi E, Bernabeu C, Smadja DM. Endoglin as an adhesion molecule in mature and progenitor endothelial cells: a function beyond TGF-β. Front Med. 2019;6:10.
34. Meng L, Lu Y, Wang X, et al. NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-β1/Smad pathways. Sci Adv. 2023;9:eadd4222.
35. Biernacka A, Cavalera M, Wang J, et al. Smad3 signaling promotes fibrosis while preserving cardiac and aortic geometry in obese diabetic mice. Circ Heart Fail. 2015;8:788-98.
37. Kanisicak O, Khalil H, Ivey MJ, et al. Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat Commun. 2016;7:12260.
38. Li Y, He Q, He CY, Cai C, Chen Z, Duan JZ. Activating transcription factor 4 drives the progression of diabetic cardiac fibrosis. ESC Heart Fail. 2023;10:2510-23.
39. Wang L, Lin L, Qi H, Chen J, Grossfeld P. Endothelial loss of ETS1 impairs coronary vascular development and leads to ventricular non-compaction. Circ Res. 2022;131:371-87.
40. Peng ML, Fu Y, Wu CW, Zhang Y, Ren H, Zhou SS. Signaling pathways related to oxidative stress in diabetic cardiomyopathy. Front Endocrinol. 2022;13:907757.
41. Zheng ZQ, Cai DH, Song YF. Identification of immune feature genes and intercellular profiles in diabetic cardiomyopathy. World J Diabetes. 2024;15:2093-110.
42. Woll AW, Quelle FW, Sigmund CD. PPARγ and retinol binding protein 7 form a regulatory hub promoting antioxidant properties of the endothelium. Physiol Genomics. 2017;49:653-8.
43. Zhang X, Fan J, Li H, Chen C, Wang Y. CD36 signaling in diabetic cardiomyopathy. Aging Dis. 2021;12:826-40.
44. Chen J, Fu Y, Day DS, et al. VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis. Nat Commun. 2017;8:383.
45. Yang X, Meyer K, Friedl A. STAT5 and prolactin participate in a positive autocrine feedback loop that promotes angiogenesis. J Biol Chem. 2013;288:21184-96.
46. Park CW, Kim HW, Lim JH, et al. 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. 2009;58:2666-76.
47. Cerychova R, Pavlinkova G. HIF-1, metabolism, and diabetes in the embryonic and adult heart. Front Endocrinol. 2018;9:460.
48. Ullah K, Wu R. Hypoxia-inducible factor regulates endothelial metabolism in cardiovascular disease. Front Physiol. 2021;12:670653.
49. Sabolová G, Kočan L, Rabajdová M, Rapčanová S, Vašková J. Association of inflammation, oxidative stress, and deteriorated cognitive functions in patients after cardiac surgery. Vessel Plus. 2024;8:27.
50. Gou W, Yue L, Tang XY, et al. Circulating proteome and progression of type 2 diabetes. J Clin Endocrinol Metab. 2022;107:1616-25.
51. Ngo D, Benson MD, Long JZ, et al. Proteomic profiling reveals biomarkers and pathways in type 2 diabetes risk. JCI Insight. 2021;6:144392.
52. Li JP, Qiu S, Tai GJ, et al. NLRP3 inflammasome-modulated angiogenic function of EPC via PI3K/ Akt/mTOR pathway in diabetic myocardial infarction. Cardiovasc Diabetol. 2025;24:6.
53. Manea SA, Todirita A, Manea A. High glucose-induced increased expression of endothelin-1 in human endothelial cells is mediated by activated CCAAT/enhancer-binding proteins. PLoS One. 2013;8:e84170.
54. Hu X, Chen W, Yang M, Li M, Li X, Ouyang S. IGFBP5 promotes EndoMT and renal fibrosis through H3K18 lactylation in diabetic nephropathy. Cell Mol Life Sci. 2025;82:215.
55. Glatz JFC, Heather LC, Luiken JJFP. CD36 as a gatekeeper of myocardial lipid metabolism and therapeutic target for metabolic disease. Physiol Rev. 2024;104:727-64.
56. Bellini S, Barutta F, Mastrocola R, Imperatore L, Bruno G, Gruden G. Heat shock proteins in vascular diabetic complications: review and future perspective. Int J Mol Sci. 2017;18:2709.
57. Horton WB, Barrett EJ. Microvascular dysfunction in diabetes mellitus and cardiometabolic disease. Endocr Rev. 2021;42:29-55.
58. Litviňuková M, Talavera-López C, Maatz H, et al. Cells of the adult human heart. Nature. 2020;588:466-72.
59. Koenig AL, Shchukina I, Amrute J, et al. Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure. Nat Cardiovasc Res. 2022;1:263-80.
60. McCracken IR, Dobie R, Bennett M, et al. Mapping the developing human cardiac endothelium at single-cell resolution identifies MECOM as a regulator of arteriovenous gene expression. Cardiovasc Res. 2022;118:2960-72.
61. Zhao G, Lu H, Liu Y, et al. Single-cell transcriptomics reveals endothelial plasticity during diabetic atherogenesis. Front Cell Dev Biol. 2021;9:689469.
62. Kalucka J, de Rooij LPMH, Goveia J, et al. Single-cell transcriptome atlas of murine endothelial cells. Cell. 2020;180:764-779.e20.
63. Skelly DA, Squiers GT, McLellan MA, et al. Single-cell transcriptional profiling reveals cellular diversity and intercommunication in the mouse heart. Cell Rep. 2018;22:600-10.
64. Zhao Q, Eichten A, Parveen A, et al. Single-cell transcriptome analyses reveal endothelial cell heterogeneity in tumors and changes following antiangiogenic treatment. Cancer Res. 2018;78:2370-82.
65. Peisker F, Halder M, Nagai J, et al. Mapping the cardiac vascular niche in heart failure. Nat Commun. 2022;13:3027.
66. Morikawa M, Derynck R, Miyazono K. TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology. Cold Spring Harb Perspect Biol. 2016;8:a021873.
67. Alvandi Z, Bischoff J. Endothelial-mesenchymal transition in cardiovascular disease. Arterioscler Thromb Vasc Biol. 2021;41:2357-69.
68. Liu Y, Zhang J, Han Q, Li Y, Xue Y, Liu X. Identification of biomarkers associated with macrophage polarization in diabetic cardiomyopathy based on bioinformatics and machine learning approaches. Life Sci. 2025;364:123443.
69. Wan A, Rodrigues B. Endothelial cell-cardiomyocyte crosstalk in diabetic cardiomyopathy. Cardiovasc Res. 2016;111:172-83.
70. Guan H, Zhao S, Fang X, et al. Frontier technologies for investigating endothelial heterogeneity and function in diabetic vascular disease: an updated review. Biomed Pharmacother. 2025;191:118445.
71. Tate M, Grieve DJ, Ritchie RH. Are targeted therapies for diabetic cardiomyopathy on the horizon? Clin Sci. 2017;131:897-915.
72. Lovisa S, Kalluri R. Fatty acid oxidation regulates the activation of endothelial-to-mesenchymal transition. Trends Mol Med. 2018;24:432-4.
73. Botros M, Fadah K, Mukherjee D. The role of inflammatory response in the development of atherosclerosis, myocardial infarction, and remodeling. Vessel Plus. 2024;8:31.
74. Zhang Z, Fang Z, Ge J, Li H. Endothelial-to-mesenchymal transition in cardiovascular diseases. Trends Mol Med. ;2025:S1471-4914(25)00113.
75. Tombor LS, John D, Glaser SF, et al. Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction. Nat Commun. 2021;12:681.
76. Martín-Bórnez M, Falcón D, Morrugares R, et al. New insights into the reparative angiogenesis after myocardial infarction. Int J Mol Sci. 2023;24:12298.
77. Dubé KN, Thomas TM, Munshaw S, Rohling M, Riley PR, Smart N. Recapitulation of developmental mechanisms to revascularize the ischemic heart. JCI Insight. 2017;2:96800.
78. Gogiraju R, Bochenek ML, Schäfer K. Angiogenic endothelial cell signaling in cardiac hypertrophy and heart failure. Front Cardiovasc Med. 2019;6:20.
79. Peng Z, Shu B, Zhang Y, Wang M. Endothelial response to pathophysiological stress. Arterioscler Thromb Vasc Biol. 2019;39:e233-43.
80. Islam S, Boström KI, Di Carlo D, et al. The mechanobiology of endothelial-to-mesenchymal transition in cardiovascular disease. Front Physiol. 2021;12:734215.
81. Csányi G, Taylor WR, Pagano PJ. NOX and inflammation in the vascular adventitia. Free Radic Biol Med. 2009;47:1254-66.
82. Lee SJ, Bae SS, Kim KH, et al. High glucose enhances MMP-2 production in adventitial fibroblasts via Akt1-dependent NF-κB pathway. FEBS Lett. 2007;581:4189-94.
83. Titus AS, Ushakumary MG, Venugopal H, Wang M, Lakatta EG, Kailasam S. Metformin attenuates hyperglycaemia-stimulated pro-fibrotic gene expression in adventitial fibroblasts via inhibition of discoidin domain receptor 2. Int J Mol Sci. 2022;24:585.
84. Tian J, Zhang M, Suo M, et al. Dapagliflozin alleviates cardiac fibrosis through suppressing EndMT and fibroblast activation via AMPKα/TGF-β/Smad signalling in type 2 diabetic rats. J Cell Mol Med. 2021;25:7642-59.
85. Yue Y, Meng K, Pu Y, Zhang X. Transforming growth factor beta (TGF-β) mediates cardiac fibrosis and induces diabetic cardiomyopathy. Diabetes Res Clin Pract. 2017;133:124-30.
86. Xiao L, Dudley AC. Fine-tuning vascular fate during endothelial-mesenchymal transition. J Pathol. 2017;241:25-35.
87. Li H, Zhu X, Cao X, Lu Y, Zhou J, Zhang X. Single-cell analysis reveals lysyl oxidase (Lox)+ fibroblast subset involved in cardiac fibrosis of diabetic mice. J Adv Res. 2023;54:223-37.
88. Zhang S, Tian W, Duan X, et al. Melatonin attenuates diabetic cardiomyopathy by increasing autophagy of cardiomyocytes via regulation of VEGF-B/GRP78/PERK signaling pathway. Cardiovasc Diabetol. 2024;23:19.
89. Lal N, Chiu AP, Wang F, et al. Loss of VEGFB and its signaling in the diabetic heart is associated with increased cell death signaling. Am J Physiol Heart Circ Physiol. 2017;312:H1163-75.
90. Xia M, Jiao L, Wang XH, et al. Single-cell RNA sequencing reveals a unique pericyte type associated with capillary dysfunction. Theranostics. 2023;13:2515-30.
91. Lee C, Chen R, Sun G, et al. VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway. Signal Transduct Target Ther. 2023;8:305.
92. Lai J, Chen F, Chen J, et al. Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling. Sci Rep. 2017;7:44473.
93. Phang RJ, Ritchie RH, Hausenloy DJ, Lees JG, Lim SY. Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy. Cardiovasc Res. 2023;119:668-90.
94. Ding M, Shi R, Du Y, et al. O-GlcNAcylation-mediated endothelial metabolic memory contributes to cardiac damage via small extracellular vesicles. Cell Metab. 2025;37:1344-1363.e6.
95. Huang JP, Chang CC, Kuo CY, et al. Exosomal microRNAs miR-30d-5p and miR-126a-5p are associated with heart failure with preserved ejection fraction in STZ-induced type 1 diabetic rats. Int J Mol Sci. 2022;23:7514.
96. Chandrasekera DNK, Neale JPH, van Hout I, et al. Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart. Apoptosis. 2020;25:388-99.
97. Veitch S, Njock MS, Chandy M, et al. MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes. Cardiovasc Diabetol. 2022;21:31.
98. Wang X, Huang W, Liu G, et al. Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. J Mol Cell Cardiol. 2014;74:139-50.
99. Lafuse WP, Wozniak DJ, Rajaram MVS. Role of cardiac macrophages on cardiac inflammation, fibrosis and tissue repair. Cells. 2020;10:51.
100. Watanabe R, Hilhorst M, Zhang H, et al. Glucose metabolism controls disease-specific signatures of macrophage effector functions. JCI Insight. 2018;3:123047.
101. Shi K, Chen X, Zhao Y, et al. Identification of potential therapeutic targets for nonischemic cardiomyopathy in European ancestry: an integrated multiomics analysis. Cardiovasc Diabetol. 2024;23:338.
102. Malhi NK, Luo Y, tang X, et al. Abstract 2005: interrogating the cross-talk: endothelial-macrophage interactions in diabetic vascular dysfunction. Arterioscler Thromb Vasc Biol. 2024;44:A2005.
103. Shi X, Liu C, Chen J, et al. Endothelial MICU1 alleviates diabetic cardiomyopathy by attenuating nitrative stress-mediated cardiac microvascular injury. Cardiovasc Diabetol. 2023;22:216.
104. Su H, Cantrell AC, Zeng H, Zhu SH, Chen JX. Emerging role of pericytes and their secretome in the heart. Cells. 2021;10:548.
105. Liu Z. Cardiac microvascular dysfunction and cardiomyopathy in diabetes: is ferroptosis a therapeutic target? Diabetes. 2023;72:313-5.
106. Simmonds SJ, Grootaert MOJ, Cuijpers I, et al. Pericyte loss initiates microvascular dysfunction in the development of diastolic dysfunction. Eur Heart J Open. 2024;4:oead129.
107. Grootaert MOJ, Pasut A, Raman J, et al. Mural cell dysfunction contributes to diastolic heart failure by promoting endothelial dysfunction and vessel remodelling. Cardiovasc Diabetol. 2025;24:62.
108. Caporali A, Martello A, Miscianinov V, Maselli D, Vono R, Spinetti G. Contribution of pericyte paracrine regulation of the endothelium to angiogenesis. Pharmacol Ther. 2017;171:56-64.
109. Zhang Q, Fang W, Ma L, Wang ZD, Yang YM, Lu YQ. VEGF levels in plasma in relation to metabolic control, inflammation, and microvascular complications in type-2 diabetes: a cohort study. Medicine. 2018;97:e0415.
110. Zhang T, Jiang D, Zhang X, et al. The role of nonmyocardial cells in the development of diabetic cardiomyopathy and the protective effects of FGF21: a current understanding. Cell Commun Signal. 2024;22:446.
112. Sheu ML, Ho FM, Yang RS, et al. High glucose induces human endothelial cell apoptosis through a phosphoinositide 3-kinase-regulated cyclooxygenase-2 pathway. Arterioscler Thromb Vasc Biol. 2005;25:539-45.
113. Paone S, Baxter AA, Hulett MD, Poon IKH. Endothelial cell apoptosis and the role of endothelial cell-derived extracellular vesicles in the progression of atherosclerosis. Cell Mol Life Sci. 2019;76:1093-106.
114. Seferović PM, Paulus WJ. Clinical diabetic cardiomyopathy: a two-faced disease with restrictive and dilated phenotypes. Eur Heart J. 2015;36:1718-27.
115. Knapp M, Tu X, Wu R. Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy. Acta Pharmacol Sin. 2019;40:1-8.
116. Camici PG, Tschöpe C, Di Carli MF, Rimoldi O, Van Linthout S. Coronary microvascular dysfunction in hypertrophy and heart failure. Cardiovasc Res. 2020;116:806-16.
117. Man S, Sanchez Duffhues G, Ten Dijke P, Baker D. The therapeutic potential of targeting the endothelial-to-mesenchymal transition. Angiogenesis. 2019;22:3-13.
118. Wang E, Wang H, Chakrabarti S. Endothelial-to-mesenchymal transition: an underappreciated mediator of diabetic complications. Front Endocrinol. 2023;14:1050540.
119. Cho JG, Lee A, Chang W, Lee MS, Kim J. Endothelial to mesenchymal transition represents a key link in the interaction between inflammation and endothelial dysfunction. Front Immunol. 2018;9:294.
120. Li C, Cai D, Yuan W, et al. The canonical Wnt/β-catenin signaling pathway upregulates carbonic anhydrase 2 via transcription factor 7-like 2 to promote cardiomyopathy in type 2 diabetic mice. Life Sci. 2025;368:123506.
121. Geng H, Guan J. MiR-18a-5p inhibits endothelial-mesenchymal transition and cardiac fibrosis through the Notch2 pathway. Biochem Biophys Res Commun. 2017;491:329-36.
122. Sánchez-Duffhues G, García de Vinuesa A, Ten Dijke P. Endothelial-to-mesenchymal transition in cardiovascular diseases: developmental signaling pathways gone awry. Dev Dyn. 2018;247:492-508.
123. Gamrat A, Surdacki MA, Chyrchel B, Surdacki A. Endothelial dysfunction: a contributor to adverse cardiovascular remodeling and heart failure development in type 2 diabetes beyond accelerated atherogenesis. J Clin Med. 2020;9:2090.
124. Kolluru GK, Bir SC, Kevil CG. Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med. 2012;2012:918267.
125. Chen D, Sindone A, Huang MLH, Peter K, Jenkins AJ. Diabetic cardiomyopathy: insights into pathophysiology, diagnosis and clinical management. J Mol Cell Cardiol. 2025;206:55-69.
126. Schmidt K, Schmidt A, Groß S, et al. SGLT2 inhibitors attenuate endothelial to mesenchymal transition and cardiac fibroblast activation. Sci Rep. 2024;14:16459.
127. Wang D, Luo P, Wang Y, et al. Glucagon-like peptide-1 protects against cardiac microvascular injury in diabetes via a cAMP/PKA/Rho-dependent mechanism. Diabetes. 2013;62:1697-708.
128. 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.
129. Wu M, Peng Z, Zu C, et al. Losartan attenuates myocardial endothelial-to-mesenchymal transition in spontaneous hypertensive rats via inhibiting TGF-β/Smad signaling. PLoS One. 2016;11:e0155730.
130. Kanasaki K, Shi S, Kanasaki M, et al. Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen. Diabetes. 2014;63:2120-31.
131. Sabe SA, Harris DD, Broadwin M, et al. Comparative effects of canagliflozin and sitagliptin in chronically ischemic myocardium. Vessel Plus. 2024;8:2.
132. Wu M, Tang RN, Liu H, Xu M, Pan MM, Liu BC. Cinacalcet attenuates the renal endothelial-to-mesenchymal transition in rats with adenine-induced renal failure. Am J Physiol Renal Physiol. 2014;306:F138-46.
133. Guo Y, Li P, Bledsoe G, Yang ZR, Chao L, Chao J. Kallistatin inhibits TGF-β-induced endothelial-mesenchymal transition by differential regulation of microRNA-21 and eNOS expression. Exp Cell Res. 2015;337:103-10.
134. Cipriani P, Di Benedetto P, Ruscitti P, et al. The endothelial-mesenchymal transition in systemic sclerosis is induced by endothelin-1 and transforming growth factor-β and may be blocked by macitentan, a dual endothelin-1 receptor antagonist. J Rheumatol. 2015;42:1808-16.
135. Hall IF, Kishta F, Xu Y, Baker AH, Kovacic JC. Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease. Cardiovasc Res. 2024;120:223-36.
136. Teng X, Ji C, Zhong H, et al. Selective deletion of endothelial cell calpain in mice reduces diabetic cardiomyopathy by improving angiogenesis. Diabetologia. 2019;62:860-72.
137. Widyantoro B, Emoto N, Nakayama K, et al. Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetic hearts through stimulation of endothelial-to-mesenchymal transition. Circulation. 2010;121:2407-18.
138. Lu S, Liao Z, Lu X, et al. Hyperglycemia acutely increases cytosolic reactive oxygen species via O-linked GlcNAcylation and CaMKII activation in mouse ventricular myocytes. Circ Res. 2020;126:e80-96.
139. Prakoso D, Lim SY, Erickson JR, et al. Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart. Cardiovasc Res. 2022;118:212-25.
140. Yao Y, Song Q, Hu C, et al. Endothelial cell metabolic memory causes cardiovascular dysfunction in diabetes. Cardiovasc Res. 2022;118:196-211.
141. Liu Y, Wang M, Su JB, et al. Potential clinical value of fibrinogen-like protein 1 as a serum biomarker for the identification of diabetic cardiomyopathy. Sci Rep. 2024;14:10311.
142. Johnson R, Nxele X, Cour M, et al. Identification of potential biomarkers for predicting the early onset of diabetic cardiomyopathy in a mouse model. Sci Rep. 2020;10:12352.
143. Li J, Qiu H, Wu Y, Su L. Identification of metabolic pathways and serum biomarkers in diabetic cardiomyopathy using untargeted metabolomics. Sci Rep. 2025;15:18718.
144. Zampetaki A, Kiechl S, Drozdov I, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010;107:810-7.
145. Prattichizzo F, De Nigris V, Sabbatinelli J, et al. CD31+ extracellular vesicles from patients with type 2 diabetes shuttle a miRNA signature associated with cardiovascular complications. Diabetes. 2021;70:240-54.
146. Prattichizzo F, Giuliani A, De Nigris V, et al. Extracellular microRNAs and endothelial hyperglycaemic memory: a therapeutic opportunity? Diabetes Obes Metab. 2016;18:855-67.
147. Rawal S, Munasinghe PE, Shindikar A, et al. Down-regulation of proangiogenic microRNA-126 and microRNA-132 are early modulators of diabetic cardiac microangiopathy. Cardiovasc Res. 2017;113:90-101.
148. Kura B, Kindernay L, Singla D, Dulova U, Bartekova M. Mechanistic insight into the role of cardiac-enriched microRNAs in diabetic heart injury. Am J Physiol Heart Circ Physiol. 2025;328:H865-84.
149. Copier CU, León L, Fernández M, Contador D, Calligaris SD. Circulating miR-19b and miR-181b are potential biomarkers for diabetic cardiomyopathy. Sci Rep. 2017;7:13514.
150. Zhu H, Leung SW. MicroRNA biomarkers of type 2 diabetes: evidence synthesis from meta-analyses and pathway modelling. Diabetologia. 2023;66:288-99.
151. Bielska A, Niemira M, Kretowski A. Recent highlights of research on miRNAs as early potential biomarkers for cardiovascular complications of type 2 diabetes mellitus. Int J Mol Sci. 2021;22:3153.
152. de Gonzalo-Calvo D, van der Meer RW, Rijzewijk LJ, et al. Serum microRNA-1 and microRNA-133a levels reflect myocardial steatosis in uncomplicated type 2 diabetes. Sci Rep. 2017;7:47.
153. Kuschnerus K, Straessler ET, Müller MF, Lüscher TF, Landmesser U, Kränkel N. Increased expression of miR-483-3p impairs the vascular response to injury in type 2 diabetes. Diabetes. 2019;68:349-60.
154. Jin ZQ. MicroRNA targets and biomarker validation for diabetes-associated cardiac fibrosis. Pharmacol Res. 2021;174:105941.
155. Liu S, Li W, Xu M, Huang H, Wang J, Chen X. Micro-RNA 21Targets dual specific phosphatase 8 to promote collagen synthesis in high glucose-treated primary cardiac fibroblasts. Can J Cardiol. 2014;30:1689-99.
156. Maiocchi S, Collins EN, Peterson AR, et al. Plasma microrna quantification protocol. Vessel Plus. 2023;7:27.
157. Cabrera-Becerra SE, Vera-Juárez G, García-Rubio VG, et al. siRNA knockdown of angiopoietin 2 significantly reduces neovascularization in diabetic rats. J Drug Target. 2022;30:673-86.
158. Waghode P, Quadir SS, Choudhary D, Sharma S, Joshi G. Small interfering RNA (siRNA) as a potential gene silencing strategy for diabetes and associated complications: challenges and future perspectives. J Diabetes Metab Disord. 2024;23:365-83.
159. Zhao Q, Shao T, Huang S, et al. The insulin-like growth factor binding protein-microfibrillar associated protein-sterol regulatory element binding protein axis regulates fibroblast-myofibroblast transition and cardiac fibrosis. Br J Pharmacol. 2024;181:2492-508.
160. Song SE, Kim YW, Kim JY, Lee DH, Kim JR, Park SY. IGFBP5 mediates high glucose-induced cardiac fibroblast activation. J Mol Endocrinol. 2013;50:291-303.
161. Cao L, Chang R, Wang X, et al. Integrative Single-cell and spatial transcriptomics reveal functional and spatial heterogeneity of atrial and ventricular cardiomyocytes in the heart. Mol Biotechnol. 2025.
162. Han S, Xu Q, Du Y, et al. Single-cell spatial transcriptomics in cardiovascular development, disease, and medicine. Genes Dis. 2024;11:101163.
163. Wang X, Sawuer G, Liang C, Lu L, Wu G. ETS1-THBS1 axis regulates macrophage polarization and exacerbates myocardial injury in diabetic cardiomyopathy. J Cardiovasc Pharmacol. 2025.
164. Sun J, Zhou R, Liu M, Zhang D. The role of myocardial fibrosis in the diabetic cardiomyopathy. Diabetol Metab Syndr. 2025;17:242.
165. Tuleta I, Frangogiannis NG. Fibrosis of the diabetic heart: clinical significance, molecular mechanisms, and therapeutic opportunities. Adv Drug Deliv Rev. 2021;176:113904.
166. Vistnes M. Hitting the Target! Challenges and opportunities for TGF-β inhibition for the treatment of cardiac fibrosis. Pharmaceuticals. 2024;17:267.
167. Lezoualc’h F, Badimon L, Baker H, et al. Diabetic cardiomyopathy: the need for adjusting experimental models to meet clinical reality. Cardiovasc Res. 2023;119:1130-45.





