ArticleProceedings of the National Academy of Sciences of the United States of America2014
Roles of cGMP-dependent protein kinase I (cGKI) and PDE5 in the regulation of Ang II-induced cardiac hypertrophy and fibrosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- Use of soluble guanylyl cyclase stimulators in heart failure therapy-a mode of action perspective.ESC heart failure · 2026Review
- Hederagenin Attenuates Cardiac Remodeling by Targeting Phosphodiesterase 9A.Phytotherapy research : PTR · 2026Article
- Proteomic surveys of the mouse heart unveil cardiovascular responses to nitric oxide/cGMP signaling deficiencies.Communications biology · 2025Article
- Angiotensin II-induced cardiac fibrosis and dysfunction are exacerbated by deletion of cGKI in periostin+ myofibroblasts.Clinical science (London, England : 1979) · 2025Article
- Downregulation of miR-214 promotes dilated Cardiomyopathy Progression through PDE5A-Mediated cGMP regulation.Scientific reports · 2024Article
- Commensal microbiome dysbiosis elicits interleukin-8 signaling to drive fibrotic skin disease.PNAS nexus · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Literature-Based Discovery to Elucidate the Biological Links between Resistant Hypertension and COVID-19.Biology · 2023Article
- Endoplasmic reticulum stress mediates homocysteine-induced hypertrophy of cardiac cells through activation of cyclic nucleotide phosphodiesterase 1C.Acta biochimica et biophysica Sinica · 2022Article
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- Sildenafil (Viagra) Aggravates the Development of Experimental Abdominal Aortic Aneurysm.Journal of the American Heart Association · 2022Article
- Guanylyl cyclase-A phosphorylation decreases cardiac hypertrophy and improves systolic function in male, but not female, mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Cyclic GMP and PKG Signaling in Heart Failure.Frontiers in pharmacology · 2022Review
- Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4).International journal of molecular sciences · 2021Article
- A nutraceutical strategy for downregulating TGFβ signalling: prospects for prevention of fibrotic disorders, including post-COVID-19 pulmonary fibrosis.Open heart · 2021Article
- An update of cyclic nucleotide phosphodiesterase as a target for cardiac diseases.Expert opinion on drug discovery · 2021Review
- Critical roles of macrophages in pressure overload-induced cardiac remodeling.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Myocardial Impact of NHE1 Regulation by Sildenafil.Frontiers in cardiovascular medicine · 2021Review
- Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1.Cells · 2020Article
- Sacubitril/Valsartan Improves Left Ventricular Function in Chronic Pressure Overload Independent of Intact Cyclic Guanosine Monophosphate-dependent Protein Kinase I Alpha Signaling.Journal of cardiac failure · 2020Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Conflicting results have been reported for the roles of cGMP and cGMP-dependent protein kinase I (cGKI) in various pathological conditions leading to cardiac hypertrophy and fibrosis. A cardioprotective effect of cGMP/cGKI has been reported in whole animals and isolated cardiomyocytes, but recent evidence from a mouse model expressing cGKIβ only in smooth muscle (βRM) but not in cardiomyocytes, endothelial cells, or fibroblasts has forced a reevaluation of the requirement for cGKI activity in the cardiomyocyte antihypertrophic effects of cGMP. In particular, βRM mice developed the same hypertrophy as WT controls when subjected to thoracic aortic constriction or isoproterenol infusion. Here, we challenged βRM and WT (Ctr) littermate control mice with angiotensin II (AII) infusion (7 d; 2 mg ⋅ kg(-1) ⋅ d(-1)) to induce hypertrophy. Both genotypes developed cardiac hypertrophy, which was more pronounced in Ctr animals. Cardiomyocyte size and interstitial fibrosis were increased equally in both genotypes. Addition of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, in the drinking water had a small effect in reducing myocyte hypertrophy in WT mice and no effect in βRM mice. However, sildenafil substantially blocked the increase in collagen I, fibronectin 1, TGFβ, and CTGF mRNA in Ctr but not in βRM hearts. These data indicate that, for the initial phase of AII-induced cardiac hypertrophy, lack of cardiomyocyte cGKI activity does not worsen hypertrophic growth. However, expression of cGKI in one or more cell types other than smooth muscle is necessary to allow the antifibrotic effect of sildenafil.
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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.