Impact of exercise training on endothelial transcriptional profiles in healthy swine: a genome-wide microarray analysis

Abstract

While the salutary effects of exercise training on conduit artery endothelial cells have been reported in animals and humans with cardiovascular risk factors or disease, whether a healthy endothelium is alterable with exercise training is less certain. The purpose of this study was to evaluate the impact of exercise training on transcriptional profiles in normal endothelial cells using a genome-wide microarray analysis. Brachial and internal mammary endothelial gene expression was compared between a group of healthy pigs that exercise trained for 16-20 wk (n = 8) and a group that remained sedentary (n = 8). We found that a total of 130 genes were upregulated and 84 genes downregulated in brachial artery endothelial cells with exercise training (>1.5-fold and false discovery rate <15%). In contrast, a total of 113 genes were upregulated and 31 genes downregulated in internal mammary artery endothelial cells using the same criteria. Although there was an overlap of 66 genes (59 upregulated and 7 downregulated with exercise training) between the brachial and internal mammary arteries, the identified endothelial gene networks and biological processes influenced by exercise training were distinctly different between the brachial and internal mammary arteries. These data indicate that a healthy endothelium is indeed responsive to exercise training and support the concept that the influence of physical activity on endothelial gene expression is not homogenously distributed throughout the vasculature.

Fig. 1.

Exercise training was associated with increased citrate synthase activity in forelimb skeletal muscles (sedentary group, n = 8; exercise-trained group, n = 8). Values are means ± SE. DELT, deltoid; TMH, triceps brachii medial head; TLH, triceps brachii long head; TLTH, triceps brachii lateral head; TAH, triceps brachii accessory head. *P < 0.05 vs. sedentary.

Fig. 2.

Impact of exercise training on endothelial transcriptional profiles in healthy swine.

Fig. 3.

Between-artery correlation in changes of gene expression induced by exercise training. Effects of exercise training produced an overlap of 66 genes between the brachial and internal mammary arteries. Each dot represents a gene. As illustrated, the direction of change for those genes was the same in both arteries (59 upregulated and 7 downregulated with exercise training). Dotted line depicts perfect agreement. EX/SED, exercise/sedentary.

Fig. 4.

Verification of microarray results by quantitative real-time PCR in a subset of brachial artery genes. Error bars indicate 95% confidence limits. *P < 0.05, significantly different between exercise-trained and sedentary pigs.

Fig. 5.

Top-scoring (and highly significant) gene networks influenced by exercise training in the brachial (left; score = 35) and internal mammary (right; score = 47) artery. Nodes represent genes/molecules, with their shape denoting the functional class of the molecule product (see legend inset). Molecules in red are those that are upregulated and molecules in green are those that are downregulated with exercise training, whereas molecules in gray are unchanged in expression but are members of the network. White molecules denote network members that were not represented on the array.