Why some hearts heal and others don’t: The phylogenetic landscape of cardiac regenerative capacity

Abstract

The limited ability of adult humans to replenish lost heart muscle cells after a heart attack has attracted scientists to explore natural heart regeneration capabilities in the animal kingdom. In particular, research has accelerated since the landmark discovery more than twenty years ago that zebrafish can completely regrow myocardial tissue. In this review, we survey heart regeneration studies in diverse model and non-model animals, aiming to gain insights into both the evolutionary trends in cardiac regenerative potential and the variations among closely related species. Differences in cardiomyogenesis, vasculature formation, and the communication between cardiovascular cells and other players have been investigated to understand the cellular basis, although the precise molecular and genetic causes underlying the stark differences in cardiac regenerative potential among certain close cousins remain largely unknown. By studying cardiovascular regeneration and repair in diverse organisms, we may uncover distinct mechanisms, offering new perspectives for advancing regenerative medicine.