Signaling pathways in cardiac fibrosis; A review and future therapeutic options

Myocardial fibrosis refers to a variety of quantitative and qualitative changes in the interstitial myocardial collagen network that occur in response to cardiac ischemic insults, systemic diseases, drugs, or any other harmful stimulus affecting the circulatory system or the heart itself. Myocardial fibrosis alters the architecture of the myocardium, facilitating the development of cardiac dysfunction, also inducing arrhythmias, influencing the clinical course and outcome of heart failure patients. Focusing on myocardial fibrosis may potentially improve patient care through the targeted diagnosis and treatment of emerging fibrotic pathways. The current review highlights the most important signaling pathways involved in the pathogenesis of cardiac fibrosis. Targeting these pathways is the key objective in introducing new therapeutic modalities to protect myocardium from remodeling and fibrosis. Present work also highlights new options currently being tested and used in mitigating fibrosis in heart. One of these options is the use of gliflozins, relatively new oral hypoglycemics, which show promising cardioprotective effects. Gliflozins are Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class approved for treatment of diabetes, which have been shown to possess a favorable metabolic profile and to significantly reduce atherosclerotic events, hospitalization for heart failure, cardiovascular and total mortality, and progression of chronic kidney disease. Although initially considered to be only glucose-lowering agents, the effects of SGLT2i have expanded far beyond that, and their use is now being studied in the treatment of heart failure and chronic kidney disease, even in patients without diabetes.