title: Chymase plays an important role in left ventricular remodeling induced by intermittent hypoxia in mice.
abstract: Intermittent hypoxia caused by sleep apnea is associated with cardiovascular disease. Chymase has been reported to play an important role in the development of cardiovascular disease, but it is unclear whether chymase is involved in the pathogenesis of left ventricular remodeling induced by intermittent hypoxia. The aim of this study was to evaluate the effect of a novel chymase inhibitor (NK3201) on hypoxia-induced left ventricular remodeling in mice. Male C57BL/6J mice (9 weeks old) were exposed to intermittent hypoxia or normoxia and were treated with NK3201 (10 mg/kg per day) or the vehicle for 10 days. Left ventricular systolic pressure showed no significant differences among all of the experimental groups. Exposure to intermittent hypoxia increased left ventricular chymase activity and angiotensin II expression, which were both suppressed by treatment with NK3201. Intermittent hypoxia also increased the mean cardiomyocyte diameter, perivascular fibrosis, expression of inflammatory cytokines, oxidative stress, and NADPH-dependent superoxide production in the left ventricular myocardium. These changes were all suppressed by NK3201 treatment. Therefore, chymase might play an important role in intermittent hypoxia-induced left ventricular remodeling, which is independent of the systemic blood pressure.
authors.affiliation: Department of Internal Medicine III, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kento
authors.initials: K
authors.lastname: Kitada
authors.forename: Chika
authors.initials: C
authors.lastname: Yamashita
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Miyamura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Mori
authors.forename: Akira
authors.initials: A
authors.lastname: Ukimura
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ohkita
authors.forename: Denan
authors.initials: D
authors.lastname: Jin
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Mizuo
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Okada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000447:Aldehydes / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D053818:Chymases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009929:Organ Size; D011743:Pyrimidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: D000081:Acetamides; D000447:Aldehydes; D015850:Interleukin-6; D008054:Lipid Peroxides; C437945:NK3201; D011743:Pyrimidines; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D000804:Angiotensin II; D009249:NADP; D053818:Chymases; C027576:4-hydroxy-2-nonenal