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 V̇O _2max (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-α, -β₁, -β₁₁ -δ, -ε, and -ζ. Results: HF diet increased total cholesterol by more than sixfold with no increase in triglycerides. Hypercholesterolemia increased PKC- β₁₁ and -ε protein levels in CCA of both male and female pig; Ex had no effect on this response. Ex-induced increases in PKC-β₁, PKC-δ, and PKC-ζ were observed in HF male pigs. Female pigs had higher baseline amounts of PKC-α (25%), PKC-β₁, (33%), PKC-β₁₁ (39%), and PKC-ε (29%), whereas male pigs had higher amounts of PKC-δ (308%). Further analyses revealed a direct relationship between androgens and PKC-δ 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.