{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:09:01Z","timestamp":1790723341988,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,1,21]]},"abstract":"\n Background<\/jats:title>\n \n Recently, we and others have reported a causal role for oxidized lipids in the pathogenesis of pulmonary hypertension (\n PH<\/jats:styled-content>\n ). However, the role of low\u2010density lipoprotein receptor (\n LDL<\/jats:styled-content>\n \u2010R) in\n PH<\/jats:styled-content>\n is not known.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We examined the role of\n LDL<\/jats:styled-content>\n \u2010R in the development of\n PH<\/jats:styled-content>\n and determined the efficacy of high\u2010density lipoprotein mimetic peptide 4F in mitigating\n PH<\/jats:styled-content>\n . Explanted human lungs and plasma from patients with PH and control subjects were analyzed for gene expression, histological characteristics, and lipoprotein oxidation. Male\n LDL<\/jats:styled-content>\n \u2010R null (\n LDL<\/jats:styled-content>\n \u2010R knockout) mice (12\u201315\u00a0months old) were fed chow, Western diet (\n WD<\/jats:styled-content>\n ),\n WD<\/jats:styled-content>\n with 4F, and\n WD<\/jats:styled-content>\n with scramble peptide for 12\u00a0weeks. Serial echocardiography, cardiac catheterization, oxidized\n LDL<\/jats:styled-content>\n assay, real\u2010time quantitative reverse transcription\u2013polymerase chain reaction, and histological analysis were performed. The effect of\n LDL<\/jats:styled-content>\n \u2010R knockdown and oxidized\n LDL<\/jats:styled-content>\n on human pulmonary artery smooth muscle cell proliferation was assessed in\u00a0vitro.\n LDL<\/jats:styled-content>\n \u2010R and\n CD<\/jats:styled-content>\n 36 expression levels were significantly downregulated in the lungs of patients with PH. Patients with PH also had increased lung lipid deposits, oxidized\n LDL<\/jats:styled-content>\n , E06 immunoreactivity, and plasma oxidized\n LDL<\/jats:styled-content>\n \/\n LDL<\/jats:styled-content>\n ratio.\n LDL<\/jats:styled-content>\n \u2010R knockout mice on\n WD<\/jats:styled-content>\n developed\n PH<\/jats:styled-content>\n , right ventricular hypertrophy, right ventricular dysfunction, pulmonary vascular remodeling, fibrosis, and lipid deposition in lungs, aortic atherosclerosis, and left ventricular dysfunction, which were prevented by 4F. Interestingly,\n PH<\/jats:styled-content>\n in\n WD<\/jats:styled-content>\n group preceded left ventricular dysfunction. Oxidized\n LDL<\/jats:styled-content>\n or\n LDL<\/jats:styled-content>\n \u2010R knockdown significantly increased proliferation of human pulmonary artery smooth muscle cells in\u00a0vitro.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Human\n PH<\/jats:styled-content>\n is associated with decreased\n LDL<\/jats:styled-content>\n \u2010R in lungs and increased oxidized\n LDL<\/jats:styled-content>\n in lungs and plasma.\n WD\u2010<\/jats:styled-content>\n fed\n LDL<\/jats:styled-content>\n \u2010R knockout mice develop\n PH<\/jats:styled-content>\n and right ventricular dysfunction, implicating a role for\n LDL<\/jats:styled-content>\n \u2010R and oxidized lipids in\n PH<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.012063","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T10:00:44Z","timestamp":1578564044000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Involvement of Low\u2010Density Lipoprotein Receptor in the Pathogenesis of Pulmonary Hypertension"],"prefix":"10.1161","volume":"9","author":[{"given":"Soban","family":"Umar","sequence":"first","affiliation":[{"name":"Department of Anesthesiology David Geffen School of Medicine at UCLA Los Angeles CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregoire","family":"Ruffenach","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology David Geffen School of Medicine at UCLA Los Angeles CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayan","family":"Moazeni","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology David 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