{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:50:27Z","timestamp":1779119427080,"version":"3.51.4"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Nitro-oxidative stress exerts a significant role in the genesis of hypoxic-ischemic (HI) brain injury. We previously reported that the \u03c9-6 long chain fatty acids, transarachidonic acids (TAAs), which are nitrative stress-induced nonenzymatically generated arachidonic acid derivatives, trigger selective microvascular endothelial cell death in neonatal neural tissue. The primary molecular target of TAAs remains unidentified. GPR40 is a G protein\u2013coupled receptor activated by long chain fatty acids, including \u03c9-6; it is highly expressed in brain, but its functions in this tissue are largely unknown. We hypothesized that TAAs play a significant role in neonatal HI-induced cerebral microvascular degeneration through GPR40 activation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Within 24 hours of a HI insult to postnatal day 7 rat pups, a cerebral infarct and a 40% decrease in cerebrovascular density was observed. These effects were associated with an increase in nitrative stress markers (3-nitrotyrosine immunoreactivity and TAA levels) and were reduced by treatment with nitric oxide synthase inhibitor. GPR40 was expressed in rat pup brain microvasculature. In vitro, in GPR40-expressing human embryonic kidney (HEK)-293 cells, [\n              <jats:sup>14<\/jats:sup>\n              C]-14\n              <jats:italic>E<\/jats:italic>\n              -AA (radiolabeled TAA) bound specifically, and TAA induced calcium transients, extracellular signal\u2013regulated kinase 1\/2 phosphorylation, and proapoptotic thrombospondin-1 expression. In vivo, intracerebroventricular injection of TAAs triggered thrombospondin-1 expression and cerebral microvascular degeneration in wild-type mice, but not in GPR40-null congeners. Additionally, HI-induced neurovascular degeneration and cerebral infarct were decreased in GPR40-null mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>GPR40 emerges as the first identified G protein\u2013coupled receptor conveying actions of nonenzymatically generated nitro-oxidative products, specifically TAAs, and is involved in (neonatal) HI encephalopathy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.112.300943","type":"journal-article","created":{"date-parts":[[2013,3,22]],"date-time":"2013-03-22T04:40:20Z","timestamp":1363927220000},"page":"954-961","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Fatty Acid Receptor Gpr40 Mediates Neuromicrovascular Degeneration Induced by Transarachidonic Acids in Rodents"],"prefix":"10.1161","volume":"33","author":[{"given":"Jean-Claude","family":"Honor\u00e9","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, Research Center - CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (J.-C.H., A.K., D.H., J.-C.R., C.Q., X.H., E.K.-D., P.H., S.C.); Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, Quebec, Canada (A.K.); Department of Pharmacology, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (J.-C.H., D.H., J.-C.R., S.C.); Montreal Diabetes Research Center - CRCHUM, Montr\u00e9al, Quebec, Canada (T.A., V.P.); Department of Medicine, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (T..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amna","family":"Kooli","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center - CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (J.-C.H., A.K., D.H., J.-C.R., C.Q., X.H., E.K.-D., P.H., S.C.); Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, Quebec, Canada (A.K.); Department of Pharmacology, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (J.-C.H., D.H., J.-C.R., S.C.); Montreal Diabetes Research Center - CRCHUM, Montr\u00e9al, Quebec, Canada (T.A., V.P.); Department of Medicine, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (T..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hamel","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center - CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (J.-C.H., A.K., D.H., J.-C.R., C.Q., X.H., E.K.-D., P.H., S.C.); Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, Quebec, Canada (A.K.); Department of Pharmacology, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (J.-C.H., D.H., J.-C.R., S.C.); Montreal Diabetes Research Center - CRCHUM, Montr\u00e9al, Quebec, Canada (T.A., V.P.); Department of Medicine, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (T..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Alquier","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center - CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (J.-C.H., A.K., D.H., J.-C.R., C.Q., X.H., E.K.-D., P.H., S.C.); Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, Quebec, Canada (A.K.); Department of Pharmacology, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (J.-C.H., D.H., J.-C.R., S.C.); Montreal Diabetes Research Center - CRCHUM, Montr\u00e9al, Quebec, Canada (T.A., V.P.); Department of Medicine, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (T..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9-Carlos","family":"Rivera","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center - CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (J.-C.H., A.K., D.H., J.-C.R., C.Q., X.H., E.K.-D., P.H., S.C.); Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, Quebec, Canada (A.K.); Department of Pharmacology, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (J.-C.H., D.H., J.-C.R., S.C.); Montreal Diabetes Research Center - CRCHUM, Montr\u00e9al, Quebec, Canada (T.A., V.P.); Department of Medicine, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (T..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Quiniou","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center - CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (J.-C.H., A.K., D.H., J.-C.R., C.Q., X.H., E.K.-D., P.H., S.C.); Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, Quebec, Canada (A.K.); Department of Pharmacology, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (J.-C.H., D.H., J.-C.R., S.C.); Montreal Diabetes Research Center - CRCHUM, Montr\u00e9al, Quebec, Canada (T.A., V.P.); Department of Medicine, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (T..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Hou","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center - CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (J.-C.H., A.K., D.H., J.-C.R., C.Q., X.H., E.K.-D., P.H., S.C.); Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, Quebec, Canada (A.K.); Department of Pharmacology, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (J.-C.H., D.H., J.-C.R., S.C.); Montreal Diabetes Research Center - CRCHUM, Montr\u00e9al, Quebec, Canada (T.A., V.P.); Department of Medicine, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (T..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsa","family":"Kermorvant-Duchemin","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center - CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (J.-C.H., A.K., D.H., J.-C.R., C.Q., X.H., E.K.-D., P.H., S.C.); Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, Quebec, Canada (A.K.); Department of Pharmacology, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (J.-C.H., D.H., J.-C.R., S.C.); Montreal Diabetes Research Center - CRCHUM, Montr\u00e9al, Quebec, Canada (T.A., V.P.); Department of Medicine, Universit\u00e9 de Montr\u00e9al, Quebec, Canada (T..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Hardy","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center - CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (J.-C.H., A.K., D.H., J.-C.R., C.Q., X.H., E.K.-D., P.H., S.C.); 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