{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:53:56Z","timestamp":1788850436691,"version":"build-2803163510"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Gene therapy, delivered directly to the blood vessel wall, could potentially prevent atherosclerotic lesion growth and promote atherosclerosis regression. Previously, we reported that a helper-dependent adenoviral (HDAd) vector expressing apolipoprotein A-I (apoA-I) in carotid endothelium of fat-fed rabbits reduced early (4 weeks) atherosclerotic lesion growth. Here, we tested whether the same HDAd\u2014delivered to the existing carotid atherosclerotic lesions\u2014could promote regression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Rabbits (n=26) were fed a high-fat diet for 7 months, then treated with bilateral carotid gene transfer. One carotid was infused with an HDAd expressing apoA-I (HDAdApoAI) and the other with a control nonexpressing HDAd (HDAdNull). The side with HDAdApoAI was randomized. Rabbits were then switched to regular chow, lowering their plasma cholesterols by over 70%. ApoA-I mRNA and protein were detected in HDAdApoAI-transduced arteries. After 7 weeks of gene therapy, compared with HDAdNull-treated arteries in the same rabbits, HDAdApoAI-treated arteries had significantly less vascular cell adhesion molecule-1 expression (28%;\n              <jats:italic>P<\/jats:italic>\n              =0.04) along with modest but statistically insignificant trends toward decreased intimal lesion volume, lipid and macrophage content, and intercellular adhesion molecule-1 expression (9%\u201321%;\n              <jats:italic>P<\/jats:italic>\n              =0.1\u20130.4). Post hoc subgroup analysis of rabbits with small-to-moderate\u2013sized lesions (n=20) showed that HDAdApoAI caused large reductions in lesion volume, lipid content, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 expression (30%\u201350%;\n              <jats:italic>P<\/jats:italic>\n              \u22640.04 for all). Macrophage content was reduced by 30% (\n              <jats:italic>P<\/jats:italic>\n              =0.06). There was a significant interaction (\n              <jats:italic>P<\/jats:italic>\n              =0.02) between lesion size and treatment efficacy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Even when administered on a background of aggressive lowering of plasma cholesterol, local HDAdApoAI vascular gene therapy may promote rapid regression of small-to-moderate\u2013sized atherosclerotic lesions.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.116.308258","type":"journal-article","created":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T03:50:26Z","timestamp":1481255426000},"page":"316-327","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Local Vascular Gene Therapy With Apolipoprotein A-I to Promote Regression of Atherosclerosis"],"prefix":"10.1161","volume":"37","author":[{"given":"Bradley 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