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In autosomal recessive Alport (ARAS) mice, ACE inhibitors double lifespan. We previously showed that deletion of\n                    <jats:italic>Itga1<\/jats:italic>\n                    in Alport mice [double\u2010knockout (DKO) mice] increased lifespan by 50%. This effect seemed dependent on the prevention of laminin 211\u2010mediated podocyte injury. Here, we treated DKO mice with vehicle or ramipril starting at 4\u2009weeks of age. Proteinuria and glomerular filtration rates were measured at 5\u2010week intervals. Glomeruli were analyzed for laminin 211 deposition in the glomerular basement membrane (GBM) and GBM ultrastructure was analyzed using transmission electron microscopy (TEM). RNA sequencing (RNA\u2010seq) was performed on isolated glomeruli at all time points and the results were compared with cultured podocytes overlaid (or not) with recombinant laminin 211. Glomerular filtration rate declined in ramipril\u2010treated DKO mice between 30 and 35\u2009weeks. Proteinuria followed these same patterns with normalization of foot process architecture in ramipril\u2010treated DKO mice. RNA\u2010seq revealed a decline in the expression of\n                    <jats:italic>Foxc2<\/jats:italic>\n                    , nephrin (\n                    <jats:italic>Nphs1<\/jats:italic>\n                    ), and podocin (\n                    <jats:italic>Nphs2<\/jats:italic>\n                    ) mRNAs, which was delayed in the ramipril\u2010treated DKO mice. GBM accumulation of laminin 211 was delayed in ramipril\u2010treated DKO mice, likely due to a role for \u03b11\u03b21 integrin in CDC42 activation in Alport mesangial cells, which is required for mesangial filopodial invasion of the subendothelial spaces of the glomerular capillary loops. Ramipril synergized with\n                    <jats:italic>Itga1<\/jats:italic>\n                    knockout, tripling lifespan compared with untreated ARAS mice. \u00a9 2023 The Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.6231","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T22:45:33Z","timestamp":1703198733000},"page":"296-309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ramipril therapy in integrin \u03b11\u2010null, autosomal recessive\n                    <scp>Alport<\/scp>\n                    mice triples lifespan: mechanistic clues from\n                    <scp>RNA<\/scp>\n                    \u2010seq analysis"],"prefix":"10.1002","volume":"262","author":[{"given":"Jacob","family":"Madison","sequence":"first","affiliation":[{"name":"Boys Town National Research Hospital  Omaha NE USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Boys Town National Research Hospital  Omaha NE 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