title: Effect of atorvastatin (Lipitor) on myocardial apoptosis and caspase-8 activation following coronary microembolization.
abstract: We determined the effect of atorvastatin on myocardial apoptosis and caspase-8 activation following coronary microembolization (CME) in a rat model. For this, 50 rats were randomly and equally divided into CME; sham-operated (control); atorvastatin lavage; gastric lavage control; and caspase-8 inhibitor (CHO) groups. In CME animals, a microembolization ball was injected through the left ventricle. Sham animals were injected with normal saline (NS). Atorvastatin group received atorvastatin gastric lavage once-a-day, 1 week before surgery. Gastric lavage controls had similar lavage with NS. CHO group was i.p-injected (CHO: 10 mg/kg) 30 min before surgery. Cardiac indices in each group were determined by echocardiography 6-h postoperatively. TUNEL assay and western blot were used for myocardial apoptosis and expression of caspases-3/-8, respectively. Echocardiography data show that left ventricular ejection fraction (LVEF) in CME group was significantly decreased (P < 0.05) compared with sham controls. Besides, left ventricular fractional shortening (FS) and cardiac output (CO) were also decreased with an increase in left ventricular end-diastolic dimension (LVEDd). Atorvastatin and CHO animals had significantly improved (P < 0.05) cardiac function compared with CME group. Myocardial apoptosis and activation levels of caspases-3/-8 were significantly increased (P < 0.05) compared with sham; myocardial apoptosis and activation levels of caspases-3/-8 were significantly decreased (P < 0.05) in atorvastatin and CHO groups compared with CME group. In conclusion, atorvastatin pretreatment suppressed post-CME myocardial apoptosis and improved cardiac function through the blockade of a myocardial death receptor-mediated apoptotic pathway.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. drlilang@163.com
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Su
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Rixin
authors.initials: R
authors.lastname: Dai
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Lu
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000069059:Atorvastatin; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects*; D004621:Embolization, Therapeutic; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053218:Receptors, Death Domain / Q000378:metabolism
chemical_list: D006538:Heptanoic Acids; D011758:Pyrroles; D053218:Receptors, Death Domain; D000069059:Atorvastatin; D053148:Caspase 3; D053181:Caspase 8