Central role of cardiac fibroblasts in myocardial fibrosis of diabetic cardiomyopathy

Abstract

Diabetic cardiomyopathy (DCM), a main cardiovascular complication of diabetes, can eventually develop into heart failure and affect the prognosis of patients. Myocardial fibrosis is the main factor causing ventricular wall stiffness and heart failure in DCM. Early control of myocardial fibrosis in DCM is of great significance to prevent or postpone the progression of DCM to heart failure. A growing body of evidence suggests that cardiomyocytes, immunocytes, and endothelial cells involve fibrogenic actions, however, cardiac fibroblasts, the main participants in collagen production, are situated in the most central position in cardiac fibrosis. In this review, we systematically elaborate the source and physiological role of myocardial fibroblasts in the context of DCM, and we also discuss the potential action and mechanism of cardiac fibroblasts in promoting fibrosis, so as to provide guidance for formulating strategies for prevention and treatment of cardiac fibrosis in DCM.

An update on chronic complications of diabetes mellitus: from molecular mechanisms to therapeutic strategies with a focus on metabolic memory

“…Elevated blood glucose stimulates inflammation, regulates immune cells, and promotes the production of cytotoxic free radicals, thereby attacking myocardial cells and vascular endothelial cells (Johnson et al 2022 ; Xie et al 2022 ). Under the action of these mechanisms triggered by high glucose, damaged cells further secrete harmful irritants, which promote the transdifferentiation of other cell types into cardiac fibroblasts (Cheng et al 2023 ). Subsequently, various adhesion molecules and adipokines, such as adiponectin, influence these fibroblasts, activating them to migrate and aggregate, thus exacerbating myocardial and vascular injury (El-Mesallamy et al 2011 ).…”

Molecular mechanisms of metabolic dysregulation in diabetic cardiomyopathy

“…Fruthermore, AGEs have the ability to alter protein structure, promote collagen cross-linking, and accelerate atherosclerosis development. The activation of AGE/RAGE signaling pathway stimulates the activaion of fibroblast and promotes fibroblast differentiation into myofibroblast, which increases extracellular matrix accumulation and accelerates pathological remodeling of diabetes heart ( 95 ).…”

Multi-modal characterisation of cardiac function and electrophysiology in type 2 diabetes: a UK Biobank cross-sectional study

“…These changes worsen progressively over time, eventually resulting in diastolic dysfunction and heart failure if left uncontrolled. Additionally, diabetes is associated with electrophysiological changes caused by the modulation of cardiac ionic currents, alterations in gap junctions, and abnormal conduction due to fibrosis [4][5][6]. Cardiac autonomic neuropathy (CAN), a common yet underdiagnosed complication of diabetes, is also responsible for altering electrophysiological function and heart rate due to damaged cardiac innervation [7].…”