ArticlePloS one2013
Increased cardiac myocyte PDE5 levels in human and murine pressure overload hypertrophy contribute to adverse LV remodeling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Long-term effect of sildenafil on echocardiographic parameters in dogs with asymptomatic myxomatous mitral valve degeneration.The Journal of veterinary medical science · 2017Trial
- The rewiring of cAMP/cGMP and LDH signalling drives cardiac hypertrophy inLife science alliance · 2025Article
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- A nutraceutical strategy for downregulating TGFβ signalling: prospects for prevention of fibrotic disorders, including post-COVID-19 pulmonary fibrosis.Open heart · 2021Article
- Myocardial Impact of NHE1 Regulation by Sildenafil.Frontiers in cardiovascular medicine · 2021Review
- Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis.International journal of molecular sciences · 2020Review
- Doxorubicin-induced chronic dilated cardiomyopathy-the apoptosis hypothesis revisited.Journal of molecular medicine (Berlin, Germany) · 2017Review
- Decreased Soluble Guanylate Cyclase Contributes to Cardiac Dysfunction Induced by Chronic Doxorubicin Treatment in Mice.Antioxidants & redox signaling · 2017Article
- Therapeutic effects of udenafil on pressure-overload cardiac hypertrophy.Hypertension research : official journal of the Japanese Society of Hypertension · 2015Article
- Right ventricular cyclic nucleotide signaling is decreased in hyperoxia-induced pulmonary hypertension in neonatal mice.American journal of physiology. Heart and circulatory physiology · 2015Article
- Myosin phosphatase isoforms and related transcripts in the pig coronary circulation and effects of exercise and chronic occlusion.Microvascular research · 2015Article
- PDE5 inhibitor efficacy is estrogen dependent in female heart disease.The Journal of clinical investigation · 2014Article
- Sex, drugs, and trial design: sex influences the heart and drug responses.The Journal of clinical investigation · 2014Article
- Therapeutic potential of PDE modulation in treating heart disease.Future medicinal chemistry · 2013Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC). METHODOLOGY/PRINCIPAL
findingsIn patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dtmax and dP/dtmin with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro. CONCLUSIONS/SIGNIFICANCE: Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target.
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