{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:48:35Z","timestamp":1790772515542,"version":"4.1.0"},"reference-count":183,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union s Horizon 2020 research and innovation programme","award":["777111"],"award-info":[{"award-number":["777111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mechanism-based therapy centred on the molecular understanding of disease-causing pathways in a given patient is still the exception rather than the rule in medicine, even in cardiology. However, recent successful drug developments centred around the second messenger cyclic guanosine-3\u2032-5\u2032-monophosphate (cGMP), which is regulating a number of cardiovascular disease modulating pathways, are about to provide novel targets for such a personalized cardiovascular therapy. Whether cGMP breakdown is inhibited or cGMP synthesis is stimulated via guanylyl cyclases or their upstream regulators in different cardiovascular disease phenotypes, the outcomes seem to be so far uniformly protective. Thus, a network of cGMP-modulating drugs has evolved that act in a mechanism-based, possibly causal manner in a number of cardiac conditions. What remains a challenge is the detection of cGMPopathy endotypes amongst cardiovascular disease phenotypes. Here, we review the growing clinical relevance of cGMP and provide a glimpse into the future on how drugs interfering with this pathway may change how we treat and diagnose cardiovascular diseases altogether.<\/jats:p>","DOI":"10.1093\/cvr\/cvab240","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T15:09:23Z","timestamp":1626275363000},"page":"2085-2102","source":"Crossref","is-referenced-by-count":54,"title":["Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1667-0266","authenticated-orcid":false,"given":"Alexandra","family":"Petraina","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Personalised Medicine, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University , Maastricht University, Universiteitssingel 50, 6229 ER Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7535-0417","authenticated-orcid":false,"given":"Cristian","family":"Nogales","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Personalised Medicine, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University , Maastricht University, Universiteitssingel 50, 6229 ER Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5907-3779","authenticated-orcid":false,"given":"Thomas","family":"Krahn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Personalised Medicine, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University , Maastricht University, Universiteitssingel 50, 6229 ER Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1491-6250","authenticated-orcid":false,"given":"Hermann","family":"Mucke","sequence":"additional","affiliation":[{"name":"H.M. 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