Donna H Korzick1, Megan E Rishel, Douglas K Bowles. 1. Noll Physiological Research Center, Intercollege Program in Physiology, The Penn State University, University Park, PA 16802, USA. dhk102@psu.edu
Abstract
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.
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.
Authors: Darla L Tharp; Isabelle Masseau; Jan Ivey; Venkataseshu K Ganjam; Douglas K Bowles Journal: Cardiovasc Res Date: 2009-01-30 Impact factor: 10.787