{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:04:25Z","timestamp":1780452265576,"version":"3.54.1"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,5,18]]},"abstract":"\n Background<\/jats:title>\n \n Carotid artery intima\/media thickness (\n IMT<\/jats:styled-content>\n ) is a hallmark trait associated with future cardiovascular events. The goal of this study was to map new genes that regulate carotid\n IMT<\/jats:styled-content>\n by genome\u2010wide association.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We induced\n IMT<\/jats:styled-content>\n by ligation procedure of the left carotid artery in 30 inbred mouse strains. Histologic reconstruction revealed significant variation in\n left carotid artery<\/jats:styled-content>\n intima, media, adventitia, external elastic lamina volumes, intima\u2010to\u2010media ratio, and (intima+media)\/\n external elastic lamina<\/jats:styled-content>\n percent ratio in inbred mice. The carotid remodeling trait was regulated by distinct genomic signatures with a dozen common single\u2010nucleotide polymorphisms associated with\n left carotid artery<\/jats:styled-content>\n intima volume, intima\u2010to\u2010media ratio, and (intima+media)\/\n external elastic lamina<\/jats:styled-content>\n percent ratio. Among genetic loci on mouse chromosomes 1, 4, and 12, there was natriuretic peptide receptor 2 (\n Npr2<\/jats:italic>\n ), a strong candidate gene. We observed that only male, not female, mice heterozygous for a targeted\n Npr2<\/jats:italic>\n deletion (\n Npr2<\/jats:italic>\n +\/\u2212<\/jats:sup>\n ) exhibited defective carotid artery remodeling compared with\n Npr2<\/jats:italic>\n wild\u2010type (\n Npr2<\/jats:italic>\n +\/+<\/jats:sup>\n ) littermates. Fibrosis in carotid\n IMT<\/jats:styled-content>\n was significantly increased in\n Npr2<\/jats:italic>\n +\/\u2212<\/jats:sup>\n males compared with\n Npr2<\/jats:italic>\n +\/\u2212<\/jats:sup>\n females or\n Npr2<\/jats:italic>\n +\/+<\/jats:sup>\n mice. We also detected decreased\n Npr2<\/jats:italic>\n expression in human atherosclerotic plaques, similar to that seen in studies in\n Npr2<\/jats:italic>\n +\/\u2212<\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We found that components of carotid\n IMT<\/jats:styled-content>\n were regulated by distinct genetic factors. We also showed a critical role for\n Npr2<\/jats:italic>\n in genetic regulation of vascular fibrosis associated with defective carotid remodeling.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.014257","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T09:55:39Z","timestamp":1589277339000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Natriuretic Peptide Receptor 2 Locus Contributes to Carotid Remodeling"],"prefix":"10.1161","volume":"9","author":[{"given":"Vyacheslav A.","family":"Korshunov","sequence":"first","affiliation":[{"name":"Department of Medicine Aab Cardiovascular Research Institute Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine M.","family":"Smolock","sequence":"additional","affiliation":[{"name":"Department of Medicine Aab Cardiovascular Research Institute Rochester 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