{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:45:24Z","timestamp":1790459124514,"version":"4.1.0"},"reference-count":208,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T00:00:00Z","timestamp":1602288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3\u2032,5\u2032-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP\/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases (CVDs). PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP\/cGMP pathways and thereby may couple chronically adverse augmented cAMP signaling with cardioprotective cGMP signaling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2- mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.<\/jats:p>","DOI":"10.3390\/ijms21207462","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T22:02:02Z","timestamp":1602626522000},"page":"7462","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Therapeutic Implications for PDE2 and cGMP\/cAMP Mediated Crosstalk in Cardiovascular Diseases"],"prefix":"10.3390","volume":"21","author":[{"given":"Mirna S.","family":"Sadek","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Carl Gustav Carus Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstra\u00dfe 74, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleder","family":"Cachorro","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Carl Gustav Carus Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstra\u00dfe 74, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"El-Armouche","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Carl Gustav Carus Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstra\u00dfe 74, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"K\u00e4mmerer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Carl Gustav Carus Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstra\u00dfe 74, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/S2214-109X(19)30318-3","article-title":"World Health Organization cardiovascular disease risk charts: Revised models to estimate risk in 21 global regions","volume":"7","author":"Kaptoge","year":"2019","journal-title":"Lancet Glob. 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