The Microenvironment of the Pathogenesis of Cardiac Hypertrophy
Farhad Bazgir,
Julia Nau,
Saeideh Nakhaei-Rad,
Ehsan Amin,
Matthew J. Wolf,
Jeffry J. Saucerman,
Kristina Lorenz,
Mohammad Reza Ahmadian
Affiliations
Farhad Bazgir
Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
Julia Nau
Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
Saeideh Nakhaei-Rad
Stem Cell Biology, and Regenerative Medicine Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad 91779-48974, Iran
Ehsan Amin
Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
Matthew J. Wolf
Department of Medicine and Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
Jeffry J. Saucerman
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA
Kristina Lorenz
Institute of Pharmacology and Toxicology, University of Würzburg, Leibniz Institute for Analytical Sciences, 97078 Würzburg, Germany
Mohammad Reza Ahmadian
Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
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.
