Abstract 643: Gender -based Differences In Left Ventricular Remodeling After Myocardial Infarction: Insight Into The Protective Role Of Integrin-linked Kinase

Abstract

There is conflicting data about gender differences with regard to left ventricular (LV) remodeling after myocardial infarction (MI). Moreover, the molecular basis for gender-based differences in LV remodeling remains unknown. This study evaluated whether gender differences exist in LV remodeling after MI. Given that integrin-linked kinase (ILK) influences LV remodeling, we also examined whether gender affects the modulation of ILK post-MI. Female and male Wistar rats were assigned to one of three groups: a sham group, a moderate MI group (size: 20-39% of LV area) and a large MI group (size: ≥40% of LV area). The MI was produced by coronary occlusion and echocardiographic analysis as well as ILK expression was performed six weeks post-MI. The MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of the left ventricle as a function of necrotic area size for both genders. However, female rats with large MI showed a lower diastolic (5.4±1 mm 2 ) and systolic dilatation (3.9±0.9 mm 2 ) than respective male rats (8.2±0.7 mm 2 and 5.7±1.1 mm 2 , respectively). Both gene (moderate MI: 1.85±0.15; large MI: 2.35±0.16, p<0.001) and protein (moderate MI: 3.21±0.09; large MI: 4.75±0.24, p<0.001) levels of ILK were increased as a function of MI size in female rats. However, only male rats in the large MI group showed an altered ILK mRNA level (moderate MI: 1.51±0.10; large MI: 1.69±0.08, p<0.001). A negative linear correlation was evident between LV dimensions and ILK protein expression in female rats with large MI (left ventricle diastolic area:ILK protein content: r 2 =0.52, p=0.003; left ventricle systolic area:ILK protein content: r 2 =0.68, p<0.001). In conclusion, post-MI ILK expression is altered in a gender-specific manner and higher ILK levels found in females may be sufficient to improve geometry of LV; however, may not be sufficient to improve LV function.