Endurance exercise training does not limit coronary atherosclerosis in familial hypercholesterolemic swine

Prospective, cohort studies in humans demonstrate that moderate to high levels of physical activity reduce both morbidity and mortality of coronary heart disease (CHD) including a decreased progression and/or regression of CHD with life‐style modification which includes exercise. However, a thorough review of both human and animal literature reveals equivocal evidence to support an intrinsic, direct exercise effect in attenuating the development of CHD. Exercise reduces development and/or causes regression of atherosclerotic lesions in mice and rabbits, however in larger mammals including primates, the evidence is more equivocal. A major limitation has been the lack of large animal models with clinically evident CHD disease. Thus, we sought to determine the effect of endurance exercise in CHD development and compensatory remodeling in a swine model of familial hypercholesterolemia (FH) that exhibits robust, complex atherosclerosis. Castrated male Rapacz familial hypercholesterolemic (FH) swine were obtained from the University of Wisconsin Swine Research and Teaching Center. Pigs were randomly assigned to either sedentary (Sed; n=9) or exercise trained (Ex; n=8) groups. At 10 months of age, Ex pigs began a 10 month treadmill‐training intervention consisting of moderate‐intensity (70% of maximal heart rate) once per day, for 5 days each week. At 14 months, all pigs were switched to a high‐fat, high‐cholesterol diet (HF; by weight 13% protein, 21.3% fat, 41.4% carbohydrate, 2% cholesterol and 1% sodium cholate). CHD was assessed by intravascular ultrasound (IVUS) both prior to (14 months of age) and after completion of 6 months on the HF diet (20 months of age). Angiograms and IVUS were obtained using standard coronary catheterization techniques. IVUS pullbacks (0.5 mm/sec; Galaxy II, Boston Scientific, 40MHz) were obtained for the proximal anterior descending (LAD) and left circumflex (LCX) arteries. For analysis, the total segment was subdivided into 3 sections and total vessel volume, lumen volume, total plaque burden volume and percent plaque burden were determined in the proximal, mid, and distal segments from 3D reconstruction (QIVUS software; Medis). Prior to HF diet, Ex resulted in a greater coronary artery size (vessel and lumen volume) in the proximal and mid sections of the LCX compared to SED, with no effect in the LAD. Relative plaque volume was minimal (~15–20% vessel area) in both Sed and Ex groups. After 6 months on HF diet, there was a 5–6 fold increase in absolute plaque volume in all segments of the LCX and LAD in both groups. Ex had no effect on absolute plaque volume at 20 months in any segment of either LCX or LAD. In both Sed and Ex groups, vessel volume was greater at 20 months compared to 14 months such that lumen volume was maintained despite the increase in plaque volume, i.e. compensatory outward remodeling was similar in both groups. Overall at 20 months, there was no significant difference in vessel volume, lumen volume, absolute or relative plaque volume in either the LCX or LAD between Sed and Ex animals. These findings fail to support an independent, direct effect of exercise in limiting CHD progression in familial hypercholesterolemia. Support or Funding Information NIH HL52490 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .