title: 7-Ketocholesterol induces the reduction of KCNMB1 in atherosclerotic blood vessels.
abstract: Hypertension is a high-risk symptom in atherosclerotic patients, and vascular rigidity is one of the main factors leading to hypertension. β1-Subunit of BKCa channel (KCNMB1; MaxiKβ1) has been reported as a modulator of vascular flexibility. To determine the relationship between atherosclerosis and KCNMB1, we studied some atherogenic factors affecting vascular tone. Blood of atherosclerotic patients shows increased concentration of 7-ketocholesterol (7K), which has been studied as a harmful lipid to blood vessels. Our data showed that KCNMB1 was significantly down-regulated in the presence of 7K, in a dose-/time-dependent manner in vascular smooth muscle cells (VSMCs). And, the reduction of KCNMB1 was confirmed in cell images of 7K-stimulated VSMCs and in vessel tissue images of ApoE knock-out mice. To determine whether aryl hydrocarbon receptor (AhR) was involved in the reduction of KCNMB1 by 7K-stimulation, protein level of AhR was analyzed by Western blot. Our data showed that the reduction of KCNMB1 was modulated through the AhR pathway. In conclusion, results of our study suggest that 7K induces the reduction of KCNMB1 through the AhR pathway.
authors.affiliation: Institute of Marine BioTechnology, Pusan National University, Busan, South Korea.
authors.forename: Yonghae
authors.initials: Y
authors.lastname: Son
authors.affiliation: Department of Pharmacology, School of Korean Medicine, Pusan National University, Busan, South Korea.
authors.forename: Wonjoo
authors.initials: W
authors.lastname: Chun
authors.affiliation: Department of Clinical Laboratory Science, Wonkwang Health Science University, Jeonbuk, South Korea.
authors.forename: Yong-Tae
authors.initials: YT
authors.lastname: Ahn
authors.affiliation: Department of Pharmacology, School of Medicine, Pusan National University, Busan, South Korea.
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
authors.affiliation: Institute of Marine BioTechnology, Pusan National University, Busan, South Korea.
authors.forename: Chul-Won
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Department of Marine Materials & Aquaculture, College of Fisheries Science, Pukyong National University, Busan, South Korea.
authors.forename: Jong-Myoung
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Aquaculture Industry Division, NFRDI, Gangneung, South Korea.
authors.forename: Chu
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Korean Medicine, Pusan National University, Busan, South Korea. Electronic address: wgan@pusan.ac.kr.
authors.forename: Won G
authors.initials: WG
authors.lastname: An
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism; D007653:Ketocholesterols / Q000378:metabolism* / Q000494:pharmacology*; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001057:Apolipoproteins E; C531905:KCNMB1 protein, human; C543091:Kcnmb1 protein, mouse; D007653:Ketocholesterols; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D018336:Receptors, Aryl Hydrocarbon; C003001:7-ketocholesterol
keywords: 7-Ketocholesterol; Atherosclerosis; HA-VSMC; Hypertension; KCNMB1