title: Role of cyclooxygenase-1 and -2 in endothelium-dependent contraction of atherosclerotic mouse abdominal aortas.
abstract: The objective of this study was to determine the role of cyclooxygenase (COX)-1 or -2 in endothelium-dependent contraction under atherosclerotic conditions. Atherosclerosis was induced in apoE knockout (apoE(-/-)) mice and those with COX-1(-/-) (apoE(-/-)-COX-1(-/-)) by feeding with high fat and cholesterol food. Aortas (abdominal or the whole section) were isolated for functional and/or biochemical analyses. As in non-atherosclerotic conditions, the muscarinic receptor agonist acetylcholine (ACh) evoked an endothelium-dependent, COX-mediated contraction following NO synthase (NOS) inhibition in abdominal aortic rings from atherosclerotic apoE(-/-) mice. Interestingly, COX-1 inhibition not only abolished such a contraction in rings showing normal appearance, but also diminished that in rings with plaques. Accordingly, only a minor contraction (<30% that of apoE(-/-) counterparts) was evoked by ACh (following NOS inhibition) in abdominal aortic rings of atherosclerotic apoE(-/-)-COX-1(-/-) mice with plaques, and none was evoked in those showing normal appearance. Also, the contraction evoked by ACh in apoE(-/-)-COX-1(-/-) abdominal aortic rings with plaques was abolished by non-selective COX inhibition, thromboxane-prostanoid (TP) receptor antagonism, or endothelial denudation. Moreover, it was noted that ACh evoked a predominant production of the prostacyclin (PGI2, which mediates abdominal aortic contraction via TP receptors in mice) metabolite 6-keto-PGF1α, which was again sensitive to COX-1 inhibition or COX-1(-/-). Therefore, in atherosclerotic mouse abdominal aortas, COX-1 can still be the major isoform mediating endothelium-dependent contraction, which probably results largely from PGI2 synthesis as in non-atherosclerotic conditions. In contrast, COX-2 may have only a minor role in such response limited to areas of plaques under the same pathological condition.
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Li
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: The Central Lab, Shantou University Medical College, Shantou, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Luo
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
authors.forename: Yingzhan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Central Lab, Shantou University Medical College, Shantou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Molecular and Cell Biology, Shantou University Medical College, Shantou, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Huang
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
authors.forename: Yingbi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051545:Cyclooxygenase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D016861:Cyclooxygenase Inhibitors; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D009569:Nitric Oxide; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D000109:Acetylcholine
keywords: PGI2 synthesis; atherosclerosis; knockout mouse; vasoconstriction