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U.S.A."],"published-print":{"date-parts":[[2018,7,31]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The morbidity and mortality associated with heart failure (HF) are unacceptably high. Cyclic guanosine-3\u2032,5\u2032-monophosphate (cGMP) plays a key role in preserving cardiac structure and function, and therapeutically targeting cGMP in HF has shown promise in experimental models and patients. Phosphodiesterases (PDEs) metabolize and curtail the actions of cGMP (and cAMP), and increased PDE activity is thought to contribute to HF pathogenesis. Herein, we show that inhibition of one specific isoform, PDE2, enhances the salutary effects of cGMP in the context of HF, and that this beneficial action facilitates a distinct pathway, driven by nitric oxide, that is impaired in this disorder. These observations validate PDE2 inhibitors as a demonstrable means of boosting cardiac cGMP and advancing HF therapy.<\/jats:p>","DOI":"10.1073\/pnas.1800996115","type":"journal-article","created":{"date-parts":[[2018,7,16]],"date-time":"2018-07-16T15:05:24Z","timestamp":1531753524000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":53,"title":["Phosphodiesterase 2 inhibition preferentially promotes NO\/guanylyl cyclase\/cGMP signaling to reverse the development of heart failure"],"prefix":"10.1073","volume":"115","author":[{"given":"Reshma S.","family":"Baliga","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, Barts &amp; The London School of Medicine &amp; Dentistry, Queen Mary University of London, EC1M 6BQ London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E. 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