{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:16:56Z","timestamp":1793643416879,"version":"4.5.1"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2019,11,8]]},"abstract":"<jats:sec>\n            <jats:title>Rationale:<\/jats:title>\n            <jats:p>Elastin is an important ECM (extracellular matrix) protein in large and small arteries. Vascular smooth muscle cells (SMCs) produce the layered elastic laminae found in elastic arteries but synthesize little elastin in muscular arteries. However, muscular arteries have a well-defined internal elastic lamina (IEL) that separates endothelial cells (ECs) from SMCs. The extent to which ECs contribute elastin to the IEL is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>To use targeted elastin (Eln) deletion in mice to explore the relative contributions of SMCs and ECs to elastic laminae formation in different arteries.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              We used SMC- and EC-specific\n              <jats:italic>Cre<\/jats:italic>\n              recombinase transgenes with a novel floxed\n              <jats:italic>Eln<\/jats:italic>\n              allele to focus gene inactivation in mice. Inactivation of\n              <jats:italic>Eln<\/jats:italic>\n              in SMCs using\n              <jats:italic>Sm22aCre<\/jats:italic>\n              resulted in depletion of elastic laminae in the arterial wall with the exception of the IEL and SMC clusters in the outer media near the adventitia. Inactivation of elastin in ECs using\n              <jats:italic>Tie2Cre<\/jats:italic>\n              or\n              <jats:italic>Cdh5Cre<\/jats:italic>\n              resulted in normal medial elastin and a typical IEL in elastic arteries. In contrast, the IEL was absent or severely disrupted in muscular arteries. Interruptions in the IEL resulted in neointimal formation in the ascending aorta but not in muscular arteries.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Combined with lineage-specific fate mapping systems, our knockout results document an unexpected heterogeneity in vascular cells that produce the elastic laminae. SMCs and ECs can independently form an IEL in most elastic arteries, whereas ECs are the major source of elastin for the IEL in muscular and resistance arteries. Neointimal formation at IEL disruptions in the ascending aorta confirms that the IEL is a critical physical barrier between SMCs and ECs in the large elastic arteries. Our studies provide new information about how SMCs and ECs contribute elastin to the arterial wall and how local elastic laminae defects may contribute to cardiovascular disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.119.315348","type":"journal-article","created":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T09:00:14Z","timestamp":1570525214000},"page":"1006-1018","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":70,"title":["Heterogeneous Cellular Contributions to Elastic Laminae Formation in Arterial Wall Development"],"prefix":"10.1161","volume":"125","author":[{"given":"Chien-Jung","family":"Lin","sequence":"first","affiliation":[{"name":"From the Department of Cell Biology and Physiology (C.-J.L., B.M.H., R.A.R., R.P.M.)"},{"name":"Department of Internal Medicine, Cardiovascular Division (C.-J.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius C.","family":"Staiculescu","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Materials Science (M.C.S., J.Z.H., J.E.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie Z.","family":"Hawes","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Materials Science (M.C.S., J.Z.H., J.E.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin J.","family":"Cocciolone","sequence":"additional","affiliation":[{"name":"Departments of Biomedical Engineering (A.J.C.), Washington University, St. Louis, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget M.","family":"Hunkins","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Physiology (C.-J.L., B.M.H., R.A.R., R.P.M.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn A.","family":"Roth","sequence":"additional","affiliation":[{"name":"From the Department 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