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The role of TGF-β in cardiac fibrosis and heart failure: A review

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Review Article

Author Details : Anil Kumar K. Prajapati, Gaurang B. Shah*

Volume : 9, Issue : 1, Year : 2024

Article Page : 1-6

https://doi.org/10.18231/j.ijcaap.2024.001

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Abstract

Chronic heart failure occurs when the heart's capacity to effectively pump blood becomes disrupted, resulting in insufficient oxygen and nutrient delivery to the body's tissues. Cardiac fibrosis, a common pathophysiological process in cardiovascular diseases like myocardial infarction and hypertension, results from the increased accumulation of extracellular matrix (ECM) by activated cardiac fibroblasts (CFs). The stimulation of fibroblasts is prompted by pro-inflammatory signaling molecules and neuroendocrine activators and ventricular wall stretch, which is observed in conditions such as pressure overload or injury following a myocardial infarction. These activated fibroblasts transform into myofibroblasts, which play a crucial role in ECM secretion and cardiac fibrosis. TGF-βs are multifunctional cytokines involved in regulating various cell processes, including inflammation, ECM deposition, cell proliferation, differentiation, and growth. TGF-β stimulation promotes myofibroblast differentiation and increases ECM protein synthesis. It also activates pro-fibrotic genes by increasing Smad2/3 while reducing inhibitory Smad 6/7 in myofibroblasts. Smad 2/3 activation has been observed in fibroblasts infiltrating remodeling hearts after injury. TGF-β further contributes to collagens I, III, and VI deposition, enhancing matrix protein expression in the heart. Despite some attempts to target TGF-β3 signaling at the ALK1-5 receptor activity level, the success has been limited. However, additional research is needed to explore and develop therapies focused on the TGF-β signaling pathway to address cardiac dysfunction and heart failure.

Keywords: Chronic Heart Failure, Cardiac Fibrosis, TGF­, Cardiac β Fibroblast, Myofibroblast

How to cite : Prajapati A K K, Shah G B, The role of TGF-β in cardiac fibrosis and heart failure: A review. IP Int J Compr Adv Pharmacol 2024;9(1):1-6

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