Abstract 15233: Exercise Reverses Endoplasmic Reticulum Stress-Associated Vascular Dysfunction in Mesentery Arteries in Atherosclerosis
Introduction: Endoplasmic reticulum (ER) stress, known as a disruption of ER homeostasis resulting in an accumulation of misfolded and unfolded protein response (UPR) is linked to cardiovascular diseases including atherosclerosis. Underlying mechanisms for mesenteric arterial dysfunction in atherosclerosis, major cause of chronic mesenteric ischemia, is unclear and no study has been done to investigate the effect of exercise on mesenteric arterial dysfunction in atherosclerosis.
Hypothesis: We hypothesized that ER stress aggravates endothelial dysfunction in mesenteric arteries in atherosclerosis and exercise ameliorate those endothelial dysfunction.
Methods: We used wild type (WT), wild type with exercise training, running on the treadmill for 12 weeks (WT-EX), apolipoprotein E knockout (ApoE KO) and ApoE KO with exercise training (ApoE KO-EX) mice. To test mesenteric artery function, endothelium-dependent (acetylcholine, ACh) vasodilation and endothelium-independent nitroprusside (SNP) vasodilation of isolated and pressurized mesenteric arteries were measured by a concentration-dependent manner. The vessels were incubated with endothelial nitric oxide synthase (eNOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), ER stress inducer tunicamycin, ER stress inhibitor, Tudca, caspase-1 inhibitor (AC-YVARD-cmk) and uncoupling protein-2 (UCP-2) inhibitor, Genepin were incubated and ACh-induced dilation was measured to investigate the underlying mechanisms.
Results: ACh-induced vasodilation was attenuated in ApoE KO compared to WT but exercise training improved the ACh-induced vasodilatation in ApoE KO-EX while endothelium-independent SNP-induced vasodilation was not different among the groups. Incubation of Tudca and AC-YVARD-cmk improved ACh-induced vasodilation in ApoE KO. ACh-induced vasodilation in the presence of L-NAME, tunicamycin and Genepin were reduced in WT, WT-EX and ApoE KO-EX, but not in ApoE KO.
Conclusions: Our findings suggest that ER stress plays a significant role in vascular endothelial dysfunction in atherosclerotic mesenteric arteries and exercise restores it through ER stress and its downstream signaling pathways including NOS, UCP-2 and caspase-1.
Author Disclosures: K. Kim: None. E. Park: None. J. Lee: None. J. Hong: None. Y. Park: None.
- © 2016 by American Heart Association, Inc.