Inter- and Intracellular Signaling Pathways

Abstract

Cardiovascular diseases, both congenital and acquired, are the leading cause of death worldwide, associated with significant health consequences and economic burden. Due to major advances in surgical procedures, most patients with congenital heart disease (CHD) survive into adulthood but suffer from previously unrecognized long-term consequences, such as early-onset heart failure. Therefore, understanding the molecular mechanisms resulting in heart defects and the lifelong complications due to hemodynamic overload are of utmost importance. Congenital heart disease arises in the first trimester of pregnancy, due to defects in the complex morphogenetic patterning of the heart. This process is coordinated through a complicated web of intercellular communication between the epicardium, the endocardium, and the myocardium. In the postnatal heart, similar crosstalk between cardiomyocytes, endothelial cells, and fibroblasts exists during pathological hemodynamic overload that emerges as a consequence of a congenital heart defect. Ultimately, communication between cells triggers the activation of intracellular signaling circuits, which allow fine coordination of cardiac development and function. Here, we review the inter- and intracellular signaling mechanisms in the heart as they were discovered mainly in genetically modified mice.