Reduction of vascular inflammation might contribute to the beneficial effects of exercise. We hypothesized that 1) exercise would reduce carotid endothelial vascular cell adhesion molecule-1 (VCAM-1) and that 2) in vivo detection of carotid inflammation can be achieved in a large animal model using contrast-enhanced ultrasound (CEU) with VCAM-1–targeted microbubbles (MBs).
Familial hypercholesterolemic (FH) swine were divided into sedentary (Sed) and exercise-trained (Ex) groups. Ex pigs underwent 16–20 wk of treadmill aerobic exercise. At the end of the study, in vivo CEU with VCAM-1–targeted MBs and assessment of endothelial-dependent dilation (EDD) were performed in carotid arteries. VCAM-1 mRNA and protein expression were compared with markers of atherosclerotic disease and health, and in vitro EDD was assessed in carotid arteries.
Exercise training neither reduced inflammation nor improved EDD in carotid arteries of FH swine. Markers of atherosclerosis including VCAM-1 were prominent in the bifurcation compared with the proximal or distal common carotid artery and inversely associated with phosphorylated and total endothelial nitric oxide synthase. Signal intensity from VCAM-1-to-control MBs positively correlated with carotid VCAM-1 protein expression, validating our technique.
These results first demonstrate that aerobic exercise has no effect on carotid endothelial inflammatory markers and EDD in FH swine. Second, our findings indicate that CEU using VCAM-1–targeted MBs can detect inflammation in vivo, providing strong foundations for longitudinal studies examining the effect of therapeutic interventions on the inflammatory status of the endothelium.
1Department of Biomedical Sciences, University of Missouri, Columbia, MO; 2Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO; and 3Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO
Address for correspondence: Douglas K. Bowles, Ph.D., E102 Veterinary Medicine, University of Missouri Columbia, MO 65211; E-mail: BowlesD@missouri.edu.
Submitted for publication March 2012.
Accepted for publication June 2012.