<p>Hypoxia-reoxygenation (H-R) injury is an important clinical phenomenon in patients with coronary artery disease (CAD). Endothelial injury is a critical step in the initiation and progression of atherosclerosis. Therefore, endothelial and cardiomyocyte protection has been considered an effective step in prevention and treatment of CAD.</p><p>To investigate the cardioprotective effect of tocopherols, omega-3 fatty acid [eicosapentaenoic acid (EPA)] and transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) during H-R, calcium tolerant myocytes isolated from adult rats were cultured and subjected to hypoxia for 24 hrs followed by reoxygenation of 3 hrs. All strategies, including tocopherol preparations, EPA and TGF-β<sub>1</sub>, showed attenuation of H-R-induced myocyte injury indicated by reduction of lactate dehydrogenase (LDH) release. Both a-tocopherol and a mixed- tocopherols (α-, γ-, and δ-) decreased the effects of H-R on iNOS expression and SOD activity in cultured myocytes. The mixed-tocopherols was more potent than a-tocopherol alone. EPA inhibited H-R-induced lipid peroxidation, MMP-1 expression and p38MAPK phosphorylation. TGF-β<sub>1</sub> blocked the increase in iNOS and PKB phosphorylation as well as the decrease in eNOS expression in cultured myocytes exposed to H-R.</p><p> To further investigate the protective effect of omega-3 fatty acids [docosahexaenoic acid (DHA) and EPA] and TGF-β<sub>1</sub>, the cultured endothelial cells were exposed to oxidant injury mediated by oxidized low-density lipoprotein (ox-LDL). Ox-LDL markedly reduced TGF-β<sub>1</sub> release, increased the expression of TGF-β<sub>1</sub> receptors, upregulated the expression of adhesion molecules, P-selectin and ICAM-1, enhanced the adhesion of monocytes to endothelial cells, and decreased protein kinase B (PKB) activation. Both DHA and EPA blocked these effects of ox-LDL on endothelial cells. Exogenous recombinant TGF-β<sub>1</sub> also ameliorated ox-LDL-induced expression of adhesion molecules and monocytes adhesion, which were blocked by antibodies to the TGF-β<sub>1</sub> type 2, but not to the type 3 receptor.</p><p>These observations provide mechanistic insights into H-R and oxidant injury and tissue protection by three different strategies.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-3769 |
| Date | January 2003 |
| Creators | Chen, Hongjiang |
| Publisher | Uppsala University, Department of Surgical Sciences, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1303 |
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