Building and re-building the heart by cardiomyocyte proliferation

Abstract

The adult human heart does not regenerate significant amounts of lost tissue after injury. Rather than making new, functional muscle, human hearts are prone to scarring and hypertrophy, which can often lead to fatal arrhythmias and heart failure. The most-cited basis of this ineffective cardiac regeneration in mammals is the low proliferative capacity of adult cardiomyocytes. However, mammalian cardiomyocytes can avidly proliferate during fetal and neonatal development, and both adult zebrafish and neonatal mice can regenerate cardiac muscle after injury, suggesting that latent regenerative potential exists. Dissecting the cellular and molecular mechanisms that promote cardiomyocyte proliferation throughout life, deciphering why proliferative capacity normally dissipates in adult mammals, and deriving means to boost this capacity are primary goals in cardiovascular research. Here, we review our current understanding of how cardiomyocyte proliferation is regulated during heart development and regeneration.

Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist

“…The recalcitrance of adult CMs to reentering the cell cycle poses a significant challenge to the development of agents that directly promote wound healing in heart tissue (18). We exploited the responsiveness of homeostatic heart tissue to WNT-974 exposure to identify Wnt-regulated cellular processes that may suppress CM cell cycle reentry.…”

Three-Dimensional and Biomimetic Technology in Cardiac Injury After Myocardial Infarction: Effect of Acellular Devices on Ventricular Function and Cardiac Remodelling

“…This study suggests that immature human heart muscle may possess an intrinsic ability to mount a regenerative response, which occurs even in the absence of inlammation and angiogenesis [77]. Other studies have emerged documenting complete functional recovery of newborn human hearts following MI [63,67,[81][82][83].…”

“…The direct reprogramming of non-muscle cells into cardiomyocyte-like cells by infecting or treating the heart with deined factors has improved. This approach was reviewed by Sadahiro et al, quoted by Foglia et al [74,82,87,88] that shows evidences about cardiac regeneration without exogenous cells.…”

Metalloproteases and Inhibitors Expression in Myocardium Under Ischemic Conditions After Allogenic Biomaterial Introduction

“…Как правило, формированию рубца в мышечной ткани способствует стремитель-ное накопление стромальных элементов и низкая скорость или отсутствие репликации мышечных кле-ток [1]. Изучение кардиопротекторных механизмов в ишемически поврежденной сердечной мышечной ткани позволяет обосновать и оптимизировать стра-тегию её восстановления и нивелировать рубец.…”