{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:24:00Z","timestamp":1790634240975,"version":"4.1.0"},"reference-count":79,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:sec id=\"jah310970-sec-0001\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Coronary artery disease due to atherosclerosis is the leading cause of death worldwide. Recent studies revealed an important role of smooth muscle cell (SMC) phenotypic switching in atherogenesis. How the extracellular matrix affects SMC phenotype in atherosclerotic lesions is not well understood. Fibronectin (Fn1) is an abundant component of the extracellular matrix in plaques and has been linked to coronary artery disease risk in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"jah310970-sec-0002\" xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We used mouse genetics combined with single\u2010cell analyses, cell lineage tracing, and immunostaining of murine and human atherosclerotic lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"jah310970-sec-0003\" xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Genetic ablation of SMC\u2010derived Fn1 in mice led to a decrease of alpha smooth muscle actin\u2010positive cells in atherosclerotic lesions and a reduced collagen content in the fibrous cap indicative of decreased plaque stability. Plaques lacking SMC\u2010derived Fn1 contained more modulated SMCs with relatively low collagen expression. Interestingly, a subset of the modulated SMCs showed high expression of NO\u2010sensitive guanylyl cyclase (NO\u2010GC). NO\u2010GC is a major cGMP generator in SMCs and like Fn1 has been implicated in coronary artery disease. Fn1 knockout SMCs showed increased cell growth and activity of the NO\u2010cGMP pathway. Expression of Fn1 and NO\u2010GC was also detected in modulated SMCs of human atherosclerotic lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"jah310970-sec-0004\" xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">SMC\u2010derived Fn1 promotes plaque stability through suppression of SMC phenotypes with low alpha smooth muscle actin and collagen expression. This atheroprotective effect might be mediated, at least in part, by a crosstalk between Fn1 and the NO\u2010cGMP axis in SMCs. Our study identifies a mechanistic link between 2 coronary artery disease risk genes, Fn1 and NO\u2010GC, which explains how the extracellular matrix regulates SMC phenotype and plaque stability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.040395","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T07:12:18Z","timestamp":1748502738000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Smooth Muscle Cell\u2010Derived Fibronectin Promotes an Atheroprotective Smooth Muscle Cell Phenotype Associated With Altered NO\u2010cGMP Signaling"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2148-8773","authenticated-orcid":false,"given":"Susanne","family":"Feil","sequence":"first","affiliation":[{"name":"University of T\u00fcbingen","place":["T\u00fcbingen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T. 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