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Alliance"],"accepted":{"date-parts":[[2025,7,3]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>\n                    Phosphodiesterase type 5a (Pde5a), an enzyme that hydrolyzes cGMP nucleotide, regulates several aspects of heart physiology and its inhibition improves left ventricular heart function under pathological conditions. We investigated Pde5a role in the development and progression of moderate and severe cardiac hypertrophy, induced by transverse aortic constriction (TAC), in Pde5a WT (\n                    <jats:italic>Pde5a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    ) and Pde5a-deficient (\n                    <jats:italic>Pde5a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) mice. Cardiac hypertrophy was surprisingly detected in\n                    <jats:italic>Pde5a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice after TAC surgery with similar alterations of cardiac function, morphology, fibrosis, and expression of molecular markers compared with\n                    <jats:italic>Pde5a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    mice. The Pde5a inhibitor, Sildenafil, prevented only moderate cardiac hypertrophy at the morpho-functional and molecular levels in\n                    <jats:italic>Pde5a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Cardiac hypertrophy was found to be associated with unbalanced cAMP\/cGMP ratio and lactate dehydrogenase plays a critical role in the metabolic remodelling of\n                    <jats:italic>Pde5a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    hearts under TAC conditions. In conclusion, pharmacological Pde5a inhibition counteracts moderate but not severe hypertrophy. Genetic ablation of Pde5a does not protect against moderate\/severe cardiac hypertrophy. In the absence of Pde5a, the oxidative metabolism shifts towards a mixed oxidative-glycolytic metabolism under TAC condition.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202403094","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T21:40:37Z","timestamp":1752529237000},"page":"e202403094","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["The rewiring of cAMP\/cGMP and LDH signalling drives cardiac hypertrophy in\n                    <i>Pde5a<\/i>\n                    <sup>\n                      <i>\u2212\/\u2212<\/i>\n                    <\/sup>\n                    mice"],"prefix":"10.26508","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0093-9379","authenticated-orcid":true,"given":"Ana Gabriela","family":"de Oliveira do R\u00eago","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02be6w209","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome","place":[", Rome, Italy"]},{"name":"Institute of Biochemistry and Cell Biology, IBBC-CNR, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7085-7996","authenticated-orcid":true,"given":"Sonia","family":"Maccari","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hssy432","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Gender Medicine, Istituto Superiore di Sanit\u00e0","place":[", Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8748-0312","authenticated-orcid":true,"given":"Giuseppe","family":"Marano","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hssy432","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Gender Medicine, Istituto Superiore di Sanit\u00e0","place":[", Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonino","family":"Stati","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hssy432","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Gender Medicine, Istituto Superiore di Sanit\u00e0","place":[", Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Saliola","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02be6w209","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology and Biotechnology \u201cC. 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