{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:11:57Z","timestamp":1790878317272,"version":"4.1.0"},"reference-count":60,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,8]]},"abstract":"<jats:p>\n                    Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is caused by biallelic loss-of-function variants in pericentrin (\n                    <jats:italic>PCNT<\/jats:italic>\n                    ), and premature coronary artery disease (CAD) is a complication of the syndrome. Histopathology of coronary arteries from patients with MOPDII who died of CAD in their 20s showed extensive atherosclerosis. Hyperlipidemic mice with smooth muscle cell\u2013specific (SMC-specific)\n                    <jats:italic>Pcnt<\/jats:italic>\n                    deficiency (\n                    <jats:italic>\n                      Pcnt\n                      <jats:sup>SMC\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) exhibited significantly greater atherosclerotic plaque burden compared with similarly treated littermate controls despite similar serum lipid levels. Loss of PCNT in SMCs induced activation of heat shock factor 1 (HSF1) and consequently upregulated the expression and activity of HMG-CoA reductase (HMGCR), the rate-limiting enzyme in cholesterol biosynthesis. The increased cholesterol biosynthesis in\n                    <jats:italic>\n                      Pcnt\n                      <jats:sup>SMC\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    SMCs augmented PERK signaling and phenotypic modulation compared with control SMCs. Treatment with the HMGCR inhibitor, pravastatin, blocked the augmented SMC modulation and reduced plaque burden in hyperlipidemic\n                    <jats:italic>\n                      Pcnt\n                      <jats:sup>SMC\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice to that of control mice. These data support the notion that\n                    <jats:italic>Pcnt<\/jats:italic>\n                    deficiency activates cellular stress to increase SMC modulation and plaque burden, and targeting this pathway with statins in patients with MOPDII has the potential to reduce CAD in these individuals. The molecular mechanism uncovered further emphasizes SMC cytosolic stress and HSF1 activation as a pathway driving atherosclerotic plaque formation independently of cholesterol levels.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.173247","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T14:00:55Z","timestamp":1699365655000},"source":"Crossref","is-referenced-by-count":9,"title":["Pericentrin deficiency in smooth muscle cells augments atherosclerosis through HSF1-driven cholesterol biosynthesis and PERK activation"],"prefix":"10.1172","volume":"8","author":[{"given":"Suravi","family":"Majumder","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijnan","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie M.","family":"Wright","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7288-9369","authenticated-orcid":true,"given":"Pujun","family":"Guan","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8386-7029","authenticated-orcid":true,"given":"L. 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