Exercise and hypercholesterolemia produce disparate shifts in coronary PKC expression

Donna Hope Korzick, Megan E. Rishel, Douglas K. Bowles

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)381-388
Number of pages8
JournalMedicine and Science in Sports and Exercise
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2005

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Hypercholesterolemia
Protein Kinase C
Coronary Disease
High Fat Diet
Swine
Protein Isoforms
Coronary Vessels
Fats
Cholesterol
Sedentary Lifestyle
Miniature Swine
Proteins
Sex Characteristics
Androgens
Triglycerides

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

@article{4c5fb45f63f1461ea028eac3f866fa2a,
title = "Exercise and hypercholesterolemia produce disparate shifts in coronary PKC expression",
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 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.",
author = "Korzick, {Donna Hope} and Rishel, {Megan E.} and Bowles, {Douglas K.}",
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Exercise and hypercholesterolemia produce disparate shifts in coronary PKC expression. / Korzick, Donna Hope; Rishel, Megan E.; Bowles, Douglas K.

In: Medicine and Science in Sports and Exercise, Vol. 37, No. 3, 01.03.2005, p. 381-388.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Exercise and hypercholesterolemia produce disparate shifts in coronary PKC expression

AU - Korzick, Donna Hope

AU - Rishel, Megan E.

AU - Bowles, Douglas K.

PY - 2005/3/1

Y1 - 2005/3/1

N2 - 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.

AB - 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.

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