{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:44:51Z","timestamp":1770745491409,"version":"3.49.0"},"reference-count":41,"publisher":"Georg Thieme Verlag KG","issue":"09","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2011]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Microvascular dysfunction occurs in insulin resistance and\/or hyperinsulinaemia. Enhanced uptake of free fatty acids (FFA) and oxidised low-density lipoproteins (oxLDL) may lead to oxidative stress and microvascular dysfunction interacting with CD36, a PPAR\u03b1\/\u03b3-regulated scavenger receptor and long-chain FFA transporter. We investigated CD36 expression and CD36-mediated oxLDL uptake before and after insulin treatment in human dermal microvascular endothelial cells (HMVECs), \u00b1 different types of fatty acids (FA), including palmitic, oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. Insulin (10\u22128 and 10\u22127 M) time-dependently increased DiI-oxLDL uptake and CD36 surface expression (by 30 \u00b1 13%, p&lt;0.05 vs. untreated control after 24 hours incubation), as assessed by ELISA and flow cytometry, an effect that was potentiated by the PI3-kinase inhibitor wortmannin and reverted by the ERK1\/2 inhibitor PD98059 and the PPAR\u03b1\/\u03b3 antagonist GW9662. A \u226524 hour exposure to 50 \u03bcM DHA or EPA, but not other FA, blunted both the constitutive (by 23 \u00b1 3% and 29 \u00b1 2%, respectively, p&lt;0.05 for both) and insulin-induced CD36 expressions (by 45 \u00b1 27 % and 12 \u00b1 3 %, respectively, p&lt;0.05 for both), along with insulin-induced uptake of DiI-oxLDL and the downregulation of phosphorylated endothelial nitric oxide synthase (P-eNOS). At gel shift assays, DHA reverted insulin-induced basal and oxLDL-stimulated transactivation of PPRE and DNA binding of PPAR\u03b1\/\u03b3 and NF-\u03baB. In conclusion, omega-3 fatty acids blunt the increased CD36 expression and activity promoted by high concentrations of insulin. Such mechanisms may be the basis for the use of omega-3 fatty acids in diabetic microvasculopathy.<\/jats:p>","DOI":"10.1160\/th10-09-0574","type":"journal-article","created":{"date-parts":[[2011,7,5]],"date-time":"2011-07-05T06:49:40Z","timestamp":1309848580000},"page":"500-510","source":"Crossref","is-referenced-by-count":27,"title":["Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPAR\u03b1\/\u03b3 activity in microvascular endothelial 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