ArticleThe Journal of clinical investigation2013
NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
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- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Transient Receptor Potential Canonical 5 (TRPC5): Regulation of Heart Rate and Protection against Pathological Cardiac Hypertrophy.Biomolecules · 2024Article
- Beyond cardiomyocytes: Cellular diversity in the heart's response to exercise.Journal of sport and health science · 2023Review
- Endothelial cell dysfunction in cardiac disease: driver or consequence?Frontiers in cell and developmental biology · 2023Review
- Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte arrhythmias and disrupts the fine-tuning of GJournal of molecular and cellular cardiology · 2022Article
- RGS6 suppresses TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4.Cell death & disease · 2022Article
- Endothelial Dysfunction in Heart Failure With Preserved Ejection Fraction: What are the Experimental Proofs?Frontiers in physiology · 2022Review
- Loss of Endothelial Hypoxia Inducible Factor-Prolyl Hydroxylase 2 Induces Cardiac Hypertrophy and Fibrosis.Journal of the American Heart Association · 2021Article
- Endothelial NADPH oxidase 4 protects against angiotensin II-induced cardiac fibrosis and inflammation.ESC heart failure · 2021Article
- Effects of NRP1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of SEMA4D.International journal of molecular medicine · 2020Article
- Low-Level Nanog Expression in the Regulation of Quiescent Endothelium.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Cardiomyocyte Proliferation and Maturation: Two Sides of the Same Coin for Heart Regeneration.Frontiers in cell and developmental biology · 2020Review
- Non-coding RNAs in Cardiac Intercellular Communication.Frontiers in physiology · 2020Review
- Heme Induces IL-6 and Cardiac Hypertrophy Genes Transcripts in Sickle Cell Mice.Frontiers in immunology · 2020Article
- The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease.Frontiers in immunology · 2020Review
- Angiogenesis and angiocrines regulating heart growth.Vascular biology (Bristol, England) · 2020Review
- Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants.Science (New York, N.Y.) · 2019Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Myocardial hypertrophy is an adaptation to increased hemodynamic demands. An increase in heart tissue must be matched by a corresponding expansion of the coronary vasculature to maintain and adequate supply of oxygen and nutrients for the heart. The physiological mechanisms that underlie the coordination of angiogenesis and cardiomyocyte growth are unknown. We report that induction of myocardial angiogenesis promotes cardiomyocyte growth and cardiac hypertrophy through a novel NO-dependent mechanism. We used transgenic, conditional overexpression of placental growth factor (PlGF) in murine cardiac tissues to stimulate myocardial angiogenesis and increase endothelial-derived NO release. NO production, in turn, induced myocardial hypertrophy by promoting proteasomal degradation of regulator of G protein signaling type 4 (RGS4), thus relieving the repression of the Gβγ/PI3Kγ/AKT/mTORC1 pathway that stimulates cardiomyocyte growth. This hypertrophic response was prevented by concomitant transgenic expression of RGS4 in cardiomyocytes. NOS inhibitor L-NAME also significantly attenuated RGS4 degradation, and reduced activation of AKT/mTORC1 signaling and induction of myocardial hypertrophy in PlGF transgenic mice, while conditional cardiac-specific PlGF expression in eNOS knockout mice did not induce myocardial hypertrophy. These findings describe a novel NO/RGS4/Gβγ/PI3Kγ/AKT mechanism that couples cardiac vessel growth with myocyte growth and heart size.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.