{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:53:53Z","timestamp":1792626833237,"version":"4.5.0"},"reference-count":69,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>cGMP plays a central role in cardiovascular regulation in health and disease. It is synthesized by NO or natriuretic peptide activated cyclases and hydrolyzed to 5\u2032GMP by select members of the PDEs (phosphodiesterase) superfamily. The primary downstream effector is cGMP-dependent protein kinase, primarily cGK-1a (cyclic GMP-dependent protein kinase 1 alpha) also known as protein kinase G 1a in the heart and vasculature. cGMP signaling is controlled in intracellular nanodomains to regulate myocyte growth, survival, metabolism, protein homeostasis, G-protein\u2013coupled receptor signaling, and other critical functions. The vascular effects of cGMP signaling have been dominated by its lowering of smooth muscle tone, but other cellular processes are also engaged. Localization of cyclases and corresponding PDEs within intracellular domains, along with their varying expression across different cell types, adds multiorgan complexity to cGMP signaling. This diversity can be leveraged therapeutically by targeting selective pathway components to impact some but not other cGMP signaling effects. Here, we review the generation and regulation of cGMP by PDEs and cyclases, focusing mainly on their role in cardiac physiology and pathophysiology. Current therapeutic uses of cGMP modulation and ongoing trials testing new potential applications are discussed.<\/jats:p>","DOI":"10.1161\/hypertensionaha.124.21709","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T05:01:26Z","timestamp":1733893286000},"page":"185-196","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Cardiac cGMP Regulation and Therapeutic Applications"],"prefix":"10.1161","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-4075","authenticated-orcid":true,"given":"Sumita","family":"Mishra","sequence":"first","affiliation":[{"name":"Center for Exercise Medicine Research, Fralin Biomedical Research Institute, (S.M., V.C.), Virginia Tech, Blacksburg, VA."},{"name":"Center for Vascular and Heart Research, Fralin Biomedical Research Institute, (S.M.), Virginia Tech, Blacksburg, VA."},{"name":"Department of Human Nutrition, Foods, and Exercise, 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