Abstract 3759: Enhanced External Counterpulsation Arrests the Progression of Atherosclerosis by Regulating Cellular Apoptosis and Proliferation Signaling Pathway
Shear stress may be the most crucial local factor affecting atherogenesis. Enhanced External Counterpulsation (EECP) has been documented to increase arterial wall shear stress in vivo. We hypothesize that chronic exposure to increased pulsatile shear stress by EECP arrests the progression of atherosclerosis due to hypercholesterolemia. Forty-eight pigs were randomized to usual diet (n = 7), high-cholesterol diet (n = 18), and high-cholesterol diet plus EECP (34±2 hours, n = 23). At week 15, the left anterior descending coronary arteries (LAD) were collected for HE staining, transmission electron microscopy examination, immunohistochemical analysis of AKT, caspase- 3 and TUNEL assay. Expression and localization of NK- κB was assessed by immunofluorescence and confocal laser scanning microscope. The aortas were isolated for Sudan staining and Western-blot analysis. Blood lipids, viscosity, Doppler ultrasound flow examination was performed. Statistical analysis was by Kruskal-Wallis and Mann-Whitney tests. During EECP, the peak diastolic arterial wall shear stress in the right brachial artery increased significantly compared with baseline (53.18±3.81 dynes/cm2 versus 23.92±2.02 dynes/cm2, p<0.001), as well as the mean arterial wall shear stress (27.46±2.22 dynes/cm2 versus 20.43±1.87 dynes/cm2, p< 0.001). High-cholesterol diet induced remarkable atherosclerotic lesions with excessive cellular proliferation and apoptosis. In comparison, hypercholesterolemic animals receiving EECP showed ameliorated atherosclerotic lesions in LADs ( lesion/medial area ratio: 19.71±3.79 % versus 7.32±1.59 %, p = 0.001) and aortas (percentage of plaque area: 9.95±1.81 % versus 5.16±1.08 %, p = 0.011), coupled with decreased TUNEL positive staining (64±2.08 % versus 49±2.27 %, p< 0.001), reduced caspase- 3 protein expression, AKT and NF- κB activity. This study demonstrates that EECP administration leads to reduced atherosclerotic lesions, coupled with dual inhibitory effects on vascular cellular proliferation and apoptosis. Its mechanisms are related to chronic increased shear stress by EECP suppressing the over-activation of the AKT/NF-κB signaling pathway.