{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:29:04Z","timestamp":1777469344611,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,1,4]],"date-time":"2018-01-04T00:00:00Z","timestamp":1515024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>\n                    Ras proteins regulate cell survival, growth, differentiation, blood pressure, and fibrosis in some organs. We have demonstrated that H\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    gene deletion produces mice hypotension\n                    <jats:italic>via<\/jats:italic>\n                    a soluble guanylate cyclase\u2010protein kinase G (PKG)\u2013dependent mechanism. In this study, we analyzed the consequences of H\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    deletion on cardiac remodeling induced by continuous angiotensin II (AngII) infusion and the molecular mechanisms implied. Left ventricular posterior wall thickness and mass and cardiomyocyte cross\u2010sectional area were similar between AngII\u2010treated H\u2010Ras knockout (H\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and control wild\u2010type (H\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) mice, as were extracellular matrix protein expression. Increased cardiac PKG\u2010I\u03b2 protein expression in H\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice suggests the involvement of this protein in heart protection.\n                    <jats:italic>Ex vivo<\/jats:italic>\n                    experiments on cardiac explants could support this mechanism, as PKG blockade blunted protection against AngII\u2010induced cardiac hypertrophy and fibrosis markers in H\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Genetic modulation studies in cardiomyocytes and cardiac and embryonic fibroblasts revealed that the lack of H\u2010Ras down\u2010regulates the B\u2010RAF\/MEK\/ERK pathway, which induces the glycogen synthase kinase\u20103\u03b2\u2010dependent activation of the transcription factor, cAMP response element\u2010binding protein, which is responsible for PKG\u2010I\u03b2 overexpression in H\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mouse embryonic fibroblasts. This study demonstrates that H\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    deletion protects against AngII\u2010induced cardiac remodeling, possibly via a mechanism in which PKG\u2010I\u03b2 overexpression could play a partial role, and points to H\u2010Ras and\/or downstream proteins as potential therapeutic targets in cardiovascular disease.\u2014Mart\u00edn\u2010S\u00e1nchez, P., Luengo, A., Griera, M., Orea, M. J., L\u00f3pez\u2010Ola\u00f1eta, M., Chiloeches, A., Lara\u2010Pezzi, E., de Frutos, S., Rodr\u00edguez\u2010Puyol, M., Calleros, L., Rodri\u00edguez\u2010Puyol, D. H\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    deletion protects against angiotensin II\u2013induced arterial hypertension and cardiac remodeling through protein kinase G\u2010I\u03b2 pathway activation.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    32, 920\u2013934 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700134rrrr","type":"journal-article","created":{"date-parts":[[2017,10,20]],"date-time":"2017-10-20T13:20:23Z","timestamp":1508505623000},"page":"920-934","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["H\u2010\n                    <i>ras<\/i>\n                    deletion protects against angiotensin II\u2013induced arterial hypertension and cardiac remodeling through protein kinase G\u2010I\u03b2 pathway activation"],"prefix":"10.1096","volume":"32","author":[{"given":"Paloma","family":"Mart\u00edn\u2010S\u00e1nchez","sequence":"first","affiliation":[{"name":"Department of Systems Biology Universidad de Alcal\u00e1 Madrid Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n en Neurol\u00f3gica (IRSIN) Madrid Spain"},{"name":"Red de Investigaci\u00f3n Renal (REDinREN) Instituto de Salud Carlos III Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia","family":"Luengo","sequence":"additional","affiliation":[{"name":"Department of Systems Biology Universidad de Alcal\u00e1 Madrid Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n en Neurol\u00f3gica (IRSIN) Madrid Spain"},{"name":"Red de Investigaci\u00f3n Renal (REDinREN) Instituto de Salud Carlos III Madrid 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