Vascular smooth muscle metabolism and pyruvate dehydrogenase

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] In dyslipidemic states, most muscle types preferentially utilize fatty acids rather than glucose largely due to modulation of the pyruvate dehydrogenase complex (PDH) activity by pyruvate dehydrogenase kinase (PDK). We have previously shown that vascular smooth muscle (VSM) does not exhibit a decrease in glucose utilization during exposure to increased levels of either short or long chain fatty acids. To determine if the metabolic inflexibility of VSM may be due to differences in the PDH regulatory mechanisms compared to other muscles, we examined the effects of the PDK inhibitor dichloroacetate (DCA) and the PDP stimulator D-chiro-inositol (DCI) on glucose utilization and lactate production in hog carotid artery (HCA). We also performed western blot analyses of hog skeletal muscle and hog VSM PDK isoforms. In the presence of DCA, a decrease in glucose utilization was observed. Western blot analyses revealed that there is 2.8 fold more PDK3 and 3.2 fold less PDK2 in VSM compared to skeletal muscle. Glucose utilization was significantly increased in the presence of insulin and DCI in VSM. The presence of PDK3 and the relative insensitivity of HCA to DCA suggests that the PDK isoforms present in VSM may contribute to the metabolic inflexibility of this tissue. Therefore, we conclude that PDH in VSM is chronically inhibited by the presence of PDK-3 and this inhibition of PDH may contribute to the metabolic inflexibility of VSM during dyslipidemia, potentially making VSM susceptible to lipotoxicity and atherosclerosis.