INTRODUCTION: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
INTRODUCTION: 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). METHODS: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. RESULTS: 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. CONCLUSION: 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.
Authors: J M Saxton; I Zwierska; K Hopkinson; E Espigares; S Choksy; S Nawaz; R Walker; A G Pockley Journal: Eur J Vasc Endovasc Surg Date: 2008-01-15 Impact factor: 7.069
Authors: Thomas H Marwick; Matthew D Hordern; Todd Miller; Deborah A Chyun; Alain G Bertoni; Roger S Blumenthal; George Philippides; Albert Rocchini Journal: Circulation Date: 2009-06-08 Impact factor: 29.690
Authors: Arturo A Arce-Esquivel; Kurt V Kreutzer; James W E Rush; James R Turk; M Harold Laughlin Journal: Med Sci Sports Exerc Date: 2012-01 Impact factor: 5.411
Authors: James R Turk; Kyle K Henderson; Gregory D Vanvickle; Justin Watkins; M Harold Laughlin Journal: Int J Exp Pathol Date: 2005-10 Impact factor: 1.925
Authors: Matthias Nahrendorf; Farouc A Jaffer; Kimberly A Kelly; David E Sosnovik; Elena Aikawa; Peter Libby; Ralph Weissleder Journal: Circulation Date: 2006-09-25 Impact factor: 29.690
Authors: Beat A Kaufmann; John M Sanders; Christopher Davis; Aris Xie; Patrick Aldred; Ian J Sarembock; Jonathan R Lindner Journal: Circulation Date: 2007-06-25 Impact factor: 29.690
Authors: Christian F Rueda-Clausen; Patricio López-Jaramillo; Carlos Luengas; Maria del Pilar Oubiña; Victoria Cachofeiro; Vicente Lahera Journal: Mediators Inflamm Date: 2009-06-23 Impact factor: 4.711
Authors: T Dylan Olver; Zachary I Grunewald; Thomas J Jurrissen; Rebecca E K MacPherson; Paul J LeBlanc; Teagan R Schnurbusch; Alana M Czajkowski; M Harold Laughlin; R Scott Rector; Shawn B Bender; Eric M Walters; Craig A Emter; Jaume Padilla Journal: Am J Physiol Regul Integr Comp Physiol Date: 2017-12-04 Impact factor: 3.619
Authors: Shiying Wang; Claudia Y Wang; Sunil Unnikrishnan; Alexander L Klibanov; John A Hossack; F William Mauldin Journal: Invest Radiol Date: 2015-11 Impact factor: 6.016
Authors: Shiying Wang; Sunil Unnikrishnan; Elizabeth B Herbst; Alexander L Klibanov; Frank William Mauldin; John A Hossack Journal: Invest Radiol Date: 2017-09 Impact factor: 6.016