Comparative Analysis of Heart Regeneration: Searching for the Key to Heal the Heart—Part I: Experimental Injury Models to Study Cardiac Regeneration

Abstract

Cardiovascular diseases are the leading cause of death worldwide, among which, ischemic heart disease is the most prevalent. Myocardial infarction results from occlusion of a coronary artery, which leads to an insufficient blood supply to the myocardium. As is well known, the massive loss of cardiomyocytes cannot be solved due the limited regenerative ability of the adult mammalian heart. In contrast, some lower vertebrate species can regenerate the heart after injury; their study has disclosed some of the involved cell types, molecular mechanisms and signaling pathways during the regenerative process. In this two-part review, we discuss the current state of the principal response in heart regeneration, where several involved processes are essential for full cardiac function in recovery.

Effects and mechanisms of the myocardial microenvironment on cardiomyocyte proliferation and regeneration

“…In both the neonatal mammalian apical resection and left anterior descending coronary artery occlusion myocardial infarction models, cardiomyocyte regeneration has been shown to restore the damaged cardiac unit ( Haubner et al, 2012 ). Subsequent series of injury models (such as ventricular resection, coronary artery ligation, and cryoinjury models) have further validated the robust regenerative capacity of cardiomyocytes in neonatal mice after injury ( Castillo-Casas et al, 2023 ). The regenerative capacity of cardiomyocytes in neonatal mammals has been validated in numerous experimental models that simulate pathological loads, including models of aseptic inflammation of the myocardium, overload models of transverse aortic constriction, and unloading models of embryos with low hematocrit ( Malek Mohammadi et al, 2019a ).…”

“…The LAD ligation murine model, a frequently utilized approach for studying MI, accurately simulates the postinfarction pathological processes through the use of permanent ligature to obstruct blood flow to the myocardium via the LAD ( Castillo-Casas et al, 2023 ). Once the heart is exposed, occlusion of the LAD effectively prevents blood flow to the affected area, while the surrounding myocardial tissue remains largely unaffected ( Fischer et al, 2022 ).…”