Dysregulations in Cardiogenic Mechanisms by TGF-beta and Angiotensin II in Cardiac Remodeling Post-Ischemic Injury: a systematic review

Objective: The objective of this study is to look into how TGF-beta and Angiotensin II disrupt cardiogenic regulators (Isl1, Brg1/Baf60-Smarcd3 complex, Nkx2-5, GATA4, Tbx5, Mef2c, HAND1/2, MYOCD, MSX2, HOPX, Wnt-signaling pathway, Notch, FGF, BMPs) during cardiac remodeling post-ischemic injury. Background: Cardiac remodeling post-ischemic injury, influenced by TGF-beta and Angiotensin II, disrupts critical cardiogenic regulators essential for heart function. Understanding these disruptions is crucial for developing targeted therapies and biomarkers to assess disease severity. This research addresses a crucial gap in cardiovascular treatment by focusing on mechanisms underlying remodeling processes, aiming to improve therapeutic strategies and outcomes for ischemic heart disease patients. Methods: Databases, including PubMed, MEDLINE, Google Scholar, and open access/ subscription based journals were searched for published articles without any date restrictions, to look into how TGF beta and Angiotensin II disrupt cardiogenic regulators in cardiac remodeling post-ischemic. Based on the criteria mentioned in the methods section, studies were systematically reviewed with focus on objectives of the study. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: Cardiac remodeling post-ischemic injury involves complex disruptions of cardiogenic regulators, prominently influenced by TGF-beta and Angiotensin II. Our study reveals these factors significantly alter critical regulators like Isl1, Nkx2.5, and GATA4, impacting myocardial repair mechanisms. TGF-beta induces fibrosis and inflammatory responses, while Angiotensin II exacerbates hypertrophic pathways and oxidative stress. Interactions between these pathways amplify remodeling through Smad, MAPK, and other signaling cascades. These findings point to the crucial roles of TGF-beta and Angiotensin II in pathological cardiac remodeling, highlighting potential targets for therapeutic interventions. Conclusion: Cardiac remodeling post-ischemic injury, influenced by TGF-beta and Angiotensin II, disrupts vital cardiogenic regulators like Isl1, Brg1/Baf60/Smarcd3 complex, Nkx2.5, GATA4, Tbx5, Mef2c, HAND1/2, MYOCD, MSX2, HOPX, Wnt-signaling pathway, Notch, FGF, and BMPs. These disruptions, involving altered receptor expression, signaling pathway interference, hypertrophic responses, and fibrosis promotion, compromise cardiac development and repair mechanisms. Targeting these pathways could enhance therapeutic strategies for ischemic heart disease by restoring normal regulator function and promoting effective cardiac repair and regeneration, thereby improving clinical outcomes.