Exercise attenuates reductions in intimal smooth muscle K + , but not Ca 2+ currents in a swine model of coronary artery disease

Abstract

Exercise has been shown to reduce mortality and in some instances regress coronary lesions in humans with coronary artery disease (CAD). Smooth muscle cell (SMC) phenotypic modulation plays a central role in coronary lesion development, and we have shown that ion channel activity can alter coronary SMC phenotype. In the current study we hypothesized, that intimal SMCs (iSMC) would exhibit reduced K+ and Ca2+channel currents compared to non-diseased coronary SMC (cSMC), and that these reductions would be attenuated by exercise. For these experiments, Rapacz Familial Hypercholesterolemic (FH) swine underwent either a prevention (PEX) or treatment (TEX) exercise protocol. PEX swine were treadmill-trained for 4 months prior to being fed a high fat diet (n=7) for 6 months, whereas TEX swine were fed the high fat diet for 6 months prior to initiating exercise (n=8) for 4 months. Other FH swine were sedentary (SED; n=10) but also fed the high fat diet for 6 months. The weight matched control (con; n=5) group did not have CAD. FH swine had elevated cholesterol (778 ± 21 mg/dL), triglycerides (96.3 ± 3.4 mg/dL), and coronary lesions (43.1 ± 1.5 % plaque by IVUS). Reduced K+ current in iSMC of FH SED (19.5 ± 3.4 pA/pF, 100mV) compared to cSMC (84.3 ± 9.3), was attenuated by TEX (40.9 ± 7.9), but not PEX (20.1 ± 2.5). Conversely, reduced L-type Ca2+channel current in iSMC of FH SED (−0.8 ± 0.3 pA/pF, 20 mV), compared to cSMC (−4.9 ± 0.5), was not attenuated by TEX (−0.9 ± 0.1) nor PEX (−0.4 ± 0.2). In conclusion, exercise may attenuate SMC phenotypic modulation and lesion progression in patients with CAD by the maintaining functional K+ channels. NIH HL52490