The Influence of the ACE I/D Polymorphism on Plasma PAI-1 Concentrations During Exercise

Abstract

1768 PURPOSE: During physical exertion, the capacity to lyse inappropriate or excessive clot (fibrinolysis) increases to protect against exertion-related ischemic events such as heart attack or stroke, which are often caused by an occlusive thrombus or clot. Increased fibrinolysis during physical exertion is partially due to a decrease in plasminogen activator inhibitor-1 (PAI-1), the main circulating inhibitor of tissue plasminogen activator. The insertion/deletion (I/D) polymorphism of the ACE gene is associated with resting plasma PAI-1 concentrations. The present study sought to investigate the METHODS: Fifty healthy, untrained males (mean + SD, age = 26 ± 5yrs, ht = 180.9 ± 8.1 cm, wt = 86.3 ± 14.6 kg) performed a maximal exercise test on a motorized treadmill. Blood samples were obtained via clean venipuncture with subjects in a semi-recumbent position prior to and immediately following exercise. Blood was drawn into an acidified citrate solution and centrifuged to obtain platelet-poor plasma. PAI-1 activity and antigen were assessed using enzyme-linked immunoadsorbant assay. DNA was extracted from whole blood and amplified by polymerase chain reaction (PCR) using allele-specific primers. PCR products were then electrophoresed in a 2% agarose gel and imaged with an ultra-violet transilluminator for genotype determination. Potential differences between subjects homozygous for the D allele (D) versus those possessing at least one I allele (I) for resting and exercise-induced PAI-1 activity and PAI-1 antigen were assessed using analysis of variance. RESULTS: There were no group differences for height, weight, age, VO2max, or peak heart rate (p>0.05). No significant difference was observed for PAI-1 antigen between groups at baseline (I = 35.8 ± 32.3 ng/ml, D = 26.4 ± 18.7 ng/ml, p>0.05) or post-exercise (I = 31.5 ± 27.6 ng/ml, D = 23.3 ± 15.6 ng/ml, p>0.05). Likewise, no differences were observed for PAI-1 activity pre-exercise (I = 12.8 ± 12.7 IU/ml, D = 13.4 ± 14.0 IU/ml, p>0.05) or post-exercise (I = 7.9 ± 8.4 IU/ml, D = 7.9 ± 9.0 IU/ml, p>0.05). No group × time interaction was observed for either PAI-1 activity or antigen. CONCLUSIONS: The ACE I/D genotype does not influence the PAI-1 response to high-intensity exercise.