{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T14:33:05Z","timestamp":1786717985808,"version":"build-2736575974"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,7,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">We examined feasibility of a unique approach towards gaining insight into heritable risk for early atherosclerosis: surveying gene expression by endothelial cells from living subjects.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Subjects aged &lt;50\u00a0years (mean age, 37; range, 22\u201349) without obstructive coronary artery disease underwent coronary reactivity testing that identified them as having normal or abnormal coronary endothelial function. Cultures of Blood Outgrowth Endothelial Cells (BOEC) from 6 normal and 13 abnormal subjects passed rigorous quality control and were used for microarray assessment of gene expression. Of 9 genes differentially expressed at false discovery rate &lt;0.1%, we here focus upon abnormal subjects having elevated expression of\n              <jats:italic>HMGB1<\/jats:italic>\n              (high mobility group box 1) which we unexpectedly found to be linked to low\n              <jats:italic>LAMC1<\/jats:italic>\n              (laminin gamma 1) expression. This linkage was corroborated by 3 of our past studies and confirmed bio\u2010functionally. Compared with normal BOEC, abnormal BOEC released 13\u00b13\u2010fold more HMGB1 in response to lipopolysaccharide; and they deposited one tenth as much LAMC1 into collagen subendothelial matrix during culture. Clinical follow\u2010up data are provided for 4 normal subjects (followed 13.4\u00b10.1\u00a0year) and for 12 abnormal subjects (followed 9.1\u00b14.5\u00a0years).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The known pathogenic effects of high\u2010\n              <jats:italic>HMGB1<\/jats:italic>\n              and low\u2010\n              <jats:italic>LAMC1<\/jats:italic>\n              predict that the combination would biologically converge upon the focal adhesion complex, to the detriment of endothelial shear responsiveness. This gene expression pattern may comprise a heritable risk state that promotes early coronary atherosclerosis. If so, the testing could be applied even in childhood, enabling early intervention. This approach offers a way to bridge the information gap between genetics and clinical phenotype.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.016134","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T09:11:29Z","timestamp":1594890689000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Abnormal Endothelial Gene Expression Associated With Early Coronary Atherosclerosis"],"prefix":"10.1161","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-7933","authenticated-orcid":false,"given":"Robert P.","family":"Hebbel","sequence":"first","affiliation":[{"name":"Division of Hematology\u2010Oncology\u2010Transplantation Department of Medicine, and Vascular Biology Center University of Minnesota Medical School Minneapolis 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