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Exercise training ameliorates coronary endothelial dysfunction in atherosclerosis through endoplasmic reticulum stress and uncoupling protein‐2
Author(s) -
Hong Junyoung,
Park Eunkyung,
Lee Jonghae,
Park Yoonjung
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.535.5
Subject(s) - endocrinology , medicine , unfolded protein response , endothelial dysfunction , vasodilation , endothelium , sodium nitroprusside , tunicamycin , chemistry , endoplasmic reticulum , nitric oxide , biochemistry
Prolonged endoplasmic reticulum (ER) stress, that has been known as an interrupted of ER homeostasis causing apoptosis and inflammation, is closely associated with cardiovascular diseases including atherosclerosis. Uncoupling protein (UCP)‐2 regulates mitochondrial reactive oxygen species (ROS) and its impairment may be associated with atherosclerosis. However, the role of ER stress and UCP‐2 in coronary endothelial dysfunction in atherosclerosis is unclear and no study has been conducted to determine the effect of exercise on ER stress and UCP‐2‐associated coronary arterioles dysfunction in atherosclerosis. Methods Wild type (WT), WT 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 were used for the study. To test coronary arterioles function, endothelium‐dependent (acetylcholine, ACh) vasodilation and endothelium‐independent nitroprusside (SNP) vasodilation of isolated and pressurized coronary arterioles 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, and uncoupling protein‐2 (UCP‐2) inhibitor, Genepin were incubated and ACh‐induced dilation were measured to investigate the underlying mechanisms. Results ACh‐induced vasodilation was attenuated in ApoE KO compared to WT, but exercise training ameliorated the ACh‐induced vasodilatation in ApoE KO‐EX while endotheliumin‐dependent SNP‐induced vasodilation was not different among the groups. 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. Conclusion Our findings suggest that exercise alleviates endothelial dysfunction in atherosclerotic coronary arterioles through the NOS, UCP‐2, and ER stress signaling pathways. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .