Leading progress in heart regeneration and repair

Abstract

Ischemic heart disease is one of the leading causes of mortality. Myocardial infarction causes loss of cardiomyocytes in the injury area accompanied by formation of a fibrotic scar. This initiates a cascade of events including further loss of myocyte, increased fibrosis, and pathological cardiac hypertrophy, eventually leading to the heart failure. Cardiomyocytes in mammals have limited regenerative potential due to post mitotic nature of cardiomyocytes. Recently, multiple studies have provided substantial insights in to the molecular pathways governing this block in adult cardiomyocyte proliferation, and successfully employed that understanding to achieve cardiac regeneration. These strategies include directly reprograming the cardiomyocytes or manipulating the cardiac interstitium to repair the injured heart. In this review, we discuss the recent advances made in the field in the past two years.

Figure 1

Cardiac regeneration and injury model. Neonatal mice heart possesses remarkable regenerative capabilities. After an MI neonatal heart shows resolution of the scar and repopulation of the area with new cardiomyocytes. Adult mice heart loses the regenerative capabilities. After an injury adult heart shows formation of fibrotic scar.

Figure 2

Summary of recent advancement toward heart regeneration. A schematic representation of factors promoting (blue box) and inhibiting (pink box) cardiac regeneration. After an injury, scar area consists of unhealthy or dead cardiomyocytes, infiltrated with immune cells and repopulation of the scar are with fibroblast. Cardiomyocyte proliferation can be achieved through inhibition of Hippo pathway, expressing cell cycle regulators in cardiomyocytes, inhibition of thyroid hormone, manipulating extracellular matrix. Cardiac regeneration can also be achieved by activating heart resident macrophages, activation of T^reg cell, increase in collateral artery and increased lymphogenesis.