Alterations in the oxidative metabolic profile in vascular smooth muscle from hyperlipidemic and diabetic swine

Tina M. Roberts, Michael Sturek, Joseph L. Dixon, Christopher D. Hardin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

High cholesterol, especially LDL cholesterol, has been associated with the development of atherosclerotic plaques in arteries. To investigate the changes in cellular substrate metabolism early in the atherogenic process, Sinclair miniature swine were treated for 12 weeks with either a control diet, a high fat diet, or a high fat diet with the addition of alloxan to induce diabetes. The fractional entry into the TCA cycle of 1,2-13C-acetate (5 mM), 1-13C-glucose (5 mM), and unlabeled, endogenous lipids was determined in control, hyperlipidemic, and diabetic/hyperlipidemic pigs using 13C-isotopomer analysis of glutamate. The diabetic state of the pigs was validated by plasma glucose measurements made after 10 weeks of alloxan treatment for control (65 ± 6 mg/dL), hyperlipidemic (63 ± 5 mg/dL), and diabetic/hyperlipidemic (333 ± 52 mg/dL) pigs. Plasma glucose values did not correlate with the percentage of glucose entry into the TCA cycle (R2 = 0.0819, n = 10). Alterations in the pattern of substrate oxidation were better correlated with changes in plasma lipids (cholesterol and triglycerides) than with changes in plasma glucose. Plasma total cholesterol and total triglyceride levels significantly correlated with changes in acetate metabolism (R2 = 0.7768 and R2 = 0.4787, respectively) and with changes in glucose metabolism (R2 = 0.6067 and R2 = 0.4506, respectively). We conclude that alterations in lipid profile, especially those that were observed in the diabetic milieu, are associated with early changes in vascular smooth muscle oxidative metabolism. These changes in oxidative metabolism may precede alterations in smooth muscle phenotype and, therefore, may play an important role in the early pathogenesis of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume217
Issue number1-2
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Metabolome
Vascular Smooth Muscle
Muscle
Metabolism
Swine
Glucose
Plasmas
Nutrition
Alloxan
Cholesterol
High Fat Diet
Lipids
Triglycerides
Acetates
Fats
Miniature Swine
Atherosclerotic Plaques
Substrates
Medical problems
LDL Cholesterol

Keywords

  • C-NMR
  • Atherosclerosis
  • Diabetes mellitus
  • Substrate utilization

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Alterations in the oxidative metabolic profile in vascular smooth muscle from hyperlipidemic and diabetic swine. / Roberts, Tina M.; Sturek, Michael; Dixon, Joseph L.; Hardin, Christopher D.

In: Molecular and Cellular Biochemistry, Vol. 217, No. 1-2, 2001, p. 99-106.

Research output: Contribution to journalArticle

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