The Microenvironment of the Pathogenesis of Cardiac Hypertrophy

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 13; p. 1780
• Main Authors: Bazgir, Farhad, Nau, Julia, Nakhaei-Rad, Saeideh, Amin, Ehsan, Wolf, Matthew J, Saucerman, Jeffry J, Lorenz, Kristina, Ahmadian, Mohammad Reza
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2023; MDPI
• Subjects: Aged patients; Analysis; Aortic stenosis; Arrhythmia; Cardiac function; cardiac hypertrophy; Cardiomegaly - pathology; Cardiomyocytes; Cardiomyopathy; Care and treatment; Cell cycle; Congestive heart failure; Diagnosis; Endothelial cells; Endothelial Cells - metabolism; Fibroblasts; Fibrosis; Growth factors; Health aspects; Heart attacks; Heart cells; Heart enlargement; Heart failure; Heart Failure - metabolism; Humans; Hypertension; Hypertrophy; Inflammation; Mathematical models; Microenvironments; Musculoskeletal system; myocardial microenvironment; Myocardium - metabolism; Myocytes, Cardiac - metabolism; myofibroblasts; Pathogenesis; Peptides; Physiological aspects; Physiology; Pregnancy; pressure overload; Proteins; Review; Risk factors; Smooth muscle; Stress (Physiology); Vasoactive agents; Germany; cardiomyocytes; heart failure; myocardial microenvironment; cardiac hypertrophy; vasoactive hormones; myofibroblasts; pressure overload; scar formation
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12131780

Pathological cardiac hypertrophy is a key risk factor for the development of heart failure and predisposes individuals to cardiac arrhythmia and sudden death. While physiological cardiac hypertrophy is adaptive, hypertrophy resulting from conditions comprising hypertension, aortic stenosis, or genetic mutations, such as hypertrophic cardiomyopathy, is maladaptive. Here, we highlight the essential role and reciprocal interactions involving both cardiomyocytes and non-myocardial cells in response to pathological conditions. Prolonged cardiovascular stress causes cardiomyocytes and non-myocardial cells to enter an activated state releasing numerous pro-hypertrophic, pro-fibrotic, and pro-inflammatory mediators such as vasoactive hormones, growth factors, and cytokines, i.e., commencing signaling events that collectively cause cardiac hypertrophy. Fibrotic remodeling is mediated by cardiac fibroblasts as the central players, but also endothelial cells and resident and infiltrating immune cells enhance these processes. Many of these hypertrophic mediators are now being integrated into computational models that provide system-level insights and will help to translate our knowledge into new pharmacological targets. This perspective article summarizes the last decades' advances in cardiac hypertrophy research and discusses the herein-involved complex myocardial microenvironment and signaling components.