title: The Effects and Mechanism of Atorvastatin on Pulmonary Hypertension Due to Left Heart Disease.
abstract: BACKGROUND
  Pulmonary hypertension due to left heart disease (PH-LHD) is one of the most common forms of PH, termed group 2 PH. Atorvastatin exerts beneficial effects on the structural remodeling of the lung in ischemic heart failure. However, few studies have investigated the effects of atorvastatin on PH due to left heart failure induced by overload.
  
  
  METHODS
  Group 2 PH was induced in animals by aortic banding. Rats (n = 20) were randomly divided into four groups: a control group (C), an aortic banding group (AOB63), an atorvastatin prevention group (AOB63/ATOR63) and an atorvastatin reversal group (AOB63/ATOR50-63). Atorvastatin was administered for 63 days after banding to the rats in the AOB63/ATOR63 group and from days 50 to 63 to the rats in the AOB63/ATOR50-63 group.
  
  
  RESULTS
  Compared with the controls, significant increases in the mean pulmonary arterial pressure, pulmonary arteriolar medial thickening, biventricular cardiac hypertrophy, wet and dry weights of the right middle lung, percentage of PCNA-positive vascular smooth muscle cells, inflammatory infiltration and expression of RhoA and Rho-kinase II were observed in the AOB63 group, and these changes concomitant with significant decreases in the percentage of TUNEL-positive vascular smooth muscle cells. Treatment of the rats in the AOB63/ATOR63 group with atorvastatin at a dose of 10 mg/kg/day significantly decreased the mean pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arteriolar medial thickness, inflammatory infiltration, percentage of PCNA-positive cells and pulmonary expression of RhoA and Rho-kinase II and significantly augmented the percentage of TUNEL-positive cells compared with the AOB63 group. However, only a trend of improvement in pulmonary vascular remodeling was detected in the AOB63/ATOR50-63 group.
  
  
  CONCLUSIONS
  Atorvastatin prevents pulmonary vascular remodeling in the PH-LHD model by down-regulating the expression of RhoA/Rho kinase, by inhibiting the proliferation and increasing the apoptosis of pulmonary arterial smooth muscle cells, and by attenuating the inflammation of pulmonary arteries.
authors.affiliation: Department of Cardiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yi-Zhan
authors.initials: YZ
authors.lastname: Guo
authors.affiliation: Department of Cardiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Jiao-Jie
authors.initials: JJ
authors.lastname: Xue
authors.affiliation: Department of Cardiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Zhi-Chong
authors.initials: ZC
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Shi-Yao
authors.initials: SY
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Mao-De
authors.initials: MD
authors.lastname: Ou
authors.affiliation: Department of Cardiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Kang-Lin
authors.initials: KL
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D017209:Apoptosis; D001160:Arterioles / Q000378:metabolism; D000069059:Atorvastatin / Q000627:therapeutic use*; D049109:Cell Proliferation; D006331:Heart Diseases / Q000188:drug therapy* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006439:Hemodynamics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007249:Inflammation; D008168:Lung / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin