Mechanisms of Cardiovascular Homeostasis and Pathophysiology--From Gene Expression, Signal Transduction to Cellular Communication

Abstract

During embryogenesis, progenitor cells are specified and differentiated into mature cardiomyocytes. Soon after birth, the ability of cardiomyocytes to proliferate is strongly restrained, and thereafter, they grow in size without cell division. Under pathological conditions, cardiomyocytes show adaptive and maladaptive responses through complex intracellular signaling pathways and cross-talking networks of intercellular and inter-tissue communications, but ultimately, they become dysfunctional and undergo cell death or degeneration. Cardiovascular diseases remain the most prevalent, costly, disabling, and deadly medical conditions. To develop novel therapies for them, it is important to elucidate the underlying mechanisms that govern gene expression, signal transduction to cellular communication. In this review article for the 2014 SATO Memorial Award, an approach to uncover molecular and cellular pathophysiology is summarized, focusing on homeobox transcription factor Nkx2-5 in the transcriptional regulation of the cardiac gene program, 3-phosphoinositide-dependent kinase-1, in the regulation of postnatal cardiomyocyte growth, survival, and function, angiotensin II type 1 receptor in the development of pathological hypertrophy and remodeling, and mast cell infiltration in the pathogenesis of atrial remodeling and fibrillation.