Exercise and hypercholesterolemia produce disparate shifts in coronary PKC expression.

INTRODUCTION

Sedentary lifestyle and high-fat, high-cholesterol diets are each associated with elevated risk for coronary heart disease (CHD); however, the mechanisms by which they increase risk are unclear. Specific PKC isoforms have been implicated in the development of CHD, regulation of coronary vasoreactivity, as well as exercise-induced cardioprotection. Thus, diet and physical inactivity may increase CHD risk by altering coronary protein kinase C (PKC) isoform profiles.

PURPOSE

To determine whether coronary PKC isoform profiles are altered in a model of early CHD and whether exercise can prevent these changes.

METHODS

Male and female Yucatan miniature swine were either fed a normal (NF) or high-fat (HF) diet (8 vs 46% kilocalories from fat) and remained sedentary (Sed) or were treadmill-trained (Ex) at 75% of; VO2max (6 mph, 60 min) for 16 wk. Groups were as follows: NFSed (N=8/N=7), NFEx (N=8/N=7), HFSed (N=8/N=7), and HFEx (N=8/N=7). Western blotting was performed on right coronary conduit artery (CCA) segments (>1 mm I.D.) to measure total protein levels of PKC-alpha, -betaI, -betaII, -delta, -epsilon, and -zeta.

RESULTS

HF diet increased total cholesterol by more than sixfold with no increase in triglycerides. Hypercholesterolemia increased PKC-betaII and -epsilon protein levels in CCA of both male and female pig; Ex had no effect on this response. Ex-induced increases in PKC-betaI, PKC-delta, and PKC-zeta were observed in HF male pigs. Female pigs had higher baseline amounts of PKC-alpha (25%), PKC-betaI (33%), PKC-betaII (39%), and PKC-epsilon (29%), whereas male pigs had higher amounts of PKC-delta (308%). Further analyses revealed a direct relationship between androgens and PKC-delta levels.

CONCLUSION

Hypercholesterolemia and exercise exert disparate effects on coronary PKC expression. Observed sex differences in PKC protein profiles may also contribute to altered cardiovascular risk patterns in males versus females.