Aortic stiffness and aerobic exercise: mechanistic insight from microarray analyses.
OBJECTIVE
Regular aerobic exercise reduces aortic stiffness. However, the mechanisms by which chronic exercise lowers arterial stiffness are not known. To determine the molecular mechanisms of these changes, the alteration of gene expression in the aorta by aerobic exercise training was measured with the microarray technique.


RESULTS
The differences in expression levels of 3800 genes in the abdominal aorta of sedentary control rats (8 wk old) and exercise-trained rats (8 wk old, treadmill running for 4 wk) were compared by the microarray analysis. Aortic pulse wave velocity (PWV) was lower and systemic arterial compliance was higher (both P < 0.05) in the exercise-trained group than in the control group. Of the 323 genes that displayed differential expression (upregulation of 206 genes and downregulation of 117 genes), a total of 29 genes (24 upregulated and 5 downregulated genes) were identified as potential candidate genes that may be involved in vasodilation and arterial destiffening. Using real-time quantitative polymerase chain reaction, we confirmed the results of microarray analysis that prostaglandin EP2 receptor (PGE-EP2R), prostaglandin EP4 receptor (PGE-EP4R), C-type natriuretic peptide (CNP), and endothelial nitric oxide synthase (eNOS) genes were differentially expressed. Furthermore, there were modest correlations between arterial stiffness and levels of these factors. Differential expression of eNOS gene was further verified at protein level by using Western blot analysis.


CONCLUSIONS
These results suggest that exercise training induces the altered expression in several genes including prostaglandin, CNP, and nitric oxide in the aorta and that these molecular changes (particularly eNOS as its protein expression was altered) may contribute, at least in part, to the beneficial effect of exercise training on aortic stiffness.
Maeda
Seiji
S
Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan. smaeda@tara.tsukuba.ac.jp
Iemitsu
Motoyuki
M
Miyauchi
Takashi
T
Kuno
Shinya
S
Matsuda
Mitsuo
M
Tanaka
Hirofumi
H
D000818:Animals; D001011:Aorta / Q000502:physiology*; D015153:Blotting, Western; D004548:Elasticity; D007150:Immunohistochemistry; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010805:Physical Conditioning, Animal; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020098:Natriuretic Peptide, C-Type; D052250:Nitric Oxide Synthase Type III