{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:47:47Z","timestamp":1775803667982,"version":"3.50.1"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2019,7,19]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Fluid shear stress (FSS) maintains NOS-3 (endothelial NO synthase) expression. Homozygosity for the C variant of the T-786C single-nucleotide polymorphism of the\n              <jats:italic>NOS3<\/jats:italic>\n              gene, which solely exists in humans, renders the gene less sensitive to FSS, resulting in a reduced endothelial cell (EC) capacity to generate NO. Decreased bioavailability of NO in the arterial vessel wall facilitates atherosclerosis. Consequently, individuals homozygous for the C variant have an increased risk for coronary heart disease (CHD).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>At least 2 compensatory mechanisms seem to minimize the deleterious effects of this single-nucleotide polymorphism in affected individuals, one of which is characterized herein.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Human genotyped umbilical vein ECs and THP-1 monocytes were used to investigate the role of 15-deoxy-\u039412,14-prostaglandin J\n              <jats:sub>2<\/jats:sub>\n              (15d-PGJ\n              <jats:sub>2<\/jats:sub>\n              ) in vitro. Its concentration in plasma samples from genotyped patients with CHD and age-matched CHD-free controls was determined using quantitative ultraperformance LC-MS\/MS. Exposure of human ECs to FSS effectively reduced monocyte transmigration particularly through monolayers of CC-genotype ECs. Primarily in CC-genotype ECs, FSS elicited a marked rise in COX (cyclooxygenase)-2 and L-PGDS (lipocalin-type prostaglandin D synthase) expression, which appeared to be NO sensitive, and provoked a significant release of 15d-PGJ\n              <jats:sub>2<\/jats:sub>\n              over baseline. Exogenous 15d-PGJ\n              <jats:sub>2<\/jats:sub>\n              significantly reduced monocyte transmigration and exerted a pronounced anti-inflammatory effect on the transmigrated monocytes by downregulating, for example, transcription of the IL (interleukin)-1\u03b2 gene (\n              <jats:italic>IL1B<\/jats:italic>\n              ). Reporter gene analyses verified that this effect is due to binding of Nrf2 (nuclear factor [erythroid-derived 2]\u2013like 2) to 2 AREs (antioxidant response elements) in the proximal\n              <jats:italic>IL1B<\/jats:italic>\n              promoter. In patients with CHD, 15d-PGJ\n              <jats:sub>2<\/jats:sub>\n              plasma levels were significantly upregulated compared with age-matched CHD-free controls, suggesting that this powerful anti-inflammatory prostanoid is part of an endogenous defence mechanism to counteract CHD.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Despite a reduced capacity to form NO, CC-genotype ECs maintain a robust anti-inflammatory phenotype through an enhanced FSS-dependent release of 15d-PGJ\n              <jats:sub>2<\/jats:sub>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.118.313820","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T09:00:14Z","timestamp":1560934814000},"page":"282-294","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["15-Deoxy-\u039412,14-Prostaglandin J\n            <sub>2<\/sub>\n            Reinforces the Anti-Inflammatory Capacity of Endothelial Cells With a Genetically Determined NO Deficit"],"prefix":"10.1161","volume":"125","author":[{"given":"Ivelina","family":"Urban","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Physiology, Heidelberg University (I.U., M.T., S.G., M.R.M., A.H.W., C.R., M.H.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Turinsky","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Physiology, Heidelberg University (I.U., M.T., S.G., M.R.M., A.H.W., C.R., M.H.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sviatlana","family":"Gehrmann","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Physiology, Heidelberg University (I.U., M.T., S.G., M.R.M., A.H.W., C.R., M.H.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Morgenstern","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I and Clinical Chemistry (J.M., M.B., T.F.), Heidelberg University Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maik","family":"Brune","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I and Clinical Chemistry (J.M., M.B., T.F.), Heidelberg University Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moritz R.","family":"Milewski","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Physiology, Heidelberg University (I.U., M.T., S.G., M.R.M., A.H.W., C.R., M.H.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas H.","family":"Wagner","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Physiology, Heidelberg University (I.U., M.T., S.G., M.R.M., A.H.W., C.R., M.H.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cordula","family":"Rumig","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Physiology, Heidelberg University (I.U., M.T., S.G., M.R.M., A.H.W., C.R., M.H.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Fleming","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I and Clinical Chemistry (J.M., M.B., T.F.), Heidelberg University Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Leuschner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumology (F.L., 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