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CLINICAL RESEARCH

Genetic Polymorphism on Endothelial Nitric Oxide Synthase Affects Endothelial Activation and Inflammatory Response During the Acute Phase of Myocardial Infarction

Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece

Manuscript received April 1, 2005; revised manuscript received May 16, 2005, accepted May 22, 2005.

^_* Reprint requests and correspondence: Dr. Dimitris Tousoulis, Athens University Medical School, S Karagiorga 69, Glifada, Athens, Greece (Email: tousouli{at}med.uoa.gr).

OBJECTIVES: This study sought to evaluate the effect of genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS); on the risk for myocardial infarction (MI); and on the release of von Willebrand factor (vWF), interleukin (IL)-6, IL-1b, and oxidized low-density lipoprotein (ox-LDL) levels during the acute phase of MI and one year after the event.

BACKGROUND: Genetic polymorphism G894T on eNOS has been associated with increased cardiovascular risk. However, its role during the acute phase of MI is unknown.

METHODS: The study population consisted of 228 patients with a first event of premature MI and 519 matched control patients. One year after the event, 61 patients and 205 control patients were recalled for the follow-up study. Blood sampling was performed during the acute phase and after one year.

RESULTS: The risk for MI in 894TT was 1.992 (95% confidence interval [CI], 1.131 to 3.485), p < 0.05 versus GG+GT; 2.038 (95% CI, 1.125 to 3.695), p < 0.05 versus GG; and 2.009 (95% CI, 1.106 to 3.651), p < 0.05 versus GT. During the acute phase, vWF was higher in GT+TT (121.02 ± 5.47%) versus GG (84.6 ± 7.1%, p < 0.01), an effect persisting after one year (90.4 ± 3.8 vs. 73.1 ± 4.6%, p < 0.01). During the acute phase, GT+TT had higher ox-LDL and IL-6 (131.2 ± 6.4 IU/l and 8.5 ± 0.7 pg/ml) compared with GG (101.7 ± 9.64 IU/l and 6.2 ± 0.8 pg/ml, p < 0.05 for both), but no difference was found at one year.

CONCLUSIONS: G894T polymorphism on the eNOS gene increases the risk for premature MI and modifies the response of vascular endothelium during the acute phase of MI by affecting the release of vWF, IL-6, and oxidative stress status, an effect diminished one year after the event.

Abbreviations and Acronyms   CABG = coronary artery bypass grafting   eNOS = endothelial nitric oxide synthase   HDL = high-density lipoprotein   IL = interleukin   MI = myocardial infarction   NO = nitric oxide   ox-LDL = oxidized low-density lipoprotein   PCI = percutaneous coronary intervention   vWF = von Willebrand factor

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