title: 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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009202:Cardiomyopathies / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication; D002470:Cell Survival; D005786:Gene Expression Regulation; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases; D015995:Prevalence; D011945:Receptors, Angiotensin / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D011945:Receptors, Angiotensin; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases