{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:06:19Z","timestamp":1784700379416,"version":"3.55.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>TRPC6 channels are expressed in endothelial cells, smooth muscle cells, and macrophages within the atherosclerotic segments of conduit blood vessels. Genetic or pharmacological inactivation of TRPC6 was variably associated with the development of atherosclerosis, a risk factor for myocardial infarction, ischemic stroke, and\/or peripheral vascular disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used two genetically matched mouse strains, ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      ;TRPC6\n                      <jats:sup>-\/-<\/jats:sup>\n                      and ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      ;TRPC6\n                      <jats:sup>+\/+<\/jats:sup>\n                      , and investigated how genetic ablation of TRPC6 affects age-dependent progression of atherosclerosis in ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice. Aortas were isolated from the mice and subjected to histopathological investigation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We assessed atherosclerotic lesion progression in mouse aortas by measuring their area, fibrous cap thickness, and calcification. We found that one-year-old mature mice had similar aortic atherosclerosis. However, aged 1.5-year-old ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      ;TRPC6\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice exhibited significantly greater atherosclerosis than ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      ;TRPC6\n                      <jats:sup>+\/+<\/jats:sup>\n                      mice. Averaged fibrous cap thickness was also larger in atherosclerotic lesions from ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      ;TRPC6\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice compared to ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      ;TRPC6\n                      <jats:sup>+\/+<\/jats:sup>\n                      mice, whereas calcification was not different between the two mouse strains at any age.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Age-dependent, spontaneous atherosclerosis progression was greater in aged but not mature ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      ;TRPC6\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice compared to ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      ;TRPC6\n                      <jats:sup>+\/+<\/jats:sup>\n                      mice. Thus, genetic ablation or chronic inhibition of TRPC6 may facilitate the development of spontaneous atherosclerosis in aged ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1884753","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:52:10Z","timestamp":1784699530000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic ablation of TRPC6 facilitated age-dependent atherosclerosis progression in an ApoE-\/- mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Isaac S.","family":"Demaree","sequence":"first","affiliation":[{"name":"Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreepadaarchana","family":"Munjuluri","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saketh","family":"Boyapalli","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan E.","family":"Beaty","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dru A.","family":"Wilkerson","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sruthilatha","family":"Sakthi Velavan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fletcher A.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Obukhov","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1177\/1358863x08094801","article-title":"Collagens in the progression and complications of atherosclerosis","volume":"14","author":"Adiguzel","year":"2009","journal-title":"Vasc. 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