Effects of pitavastatin on pressure overload-induced heart failure in mice.

Abstract

BACKGROUND:

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), which are widely used to lower plasma cholesterol levels, have been reported to have various pleiotropic effects such as protective effect of endothelial cells, angiogenic effect, antioxidant effect and anti-inflammatory effect. It is unclear, however, whether statins have any effects on the progression from left ventricular (LV) hypertrophy to heart failure in the established hypertrophied heart.

METHODS AND RESULTS:

C57BL/6 mice were treated with pitavastatin (pitava) or vehicle (control) from 2 weeks (established hypertrophy stage) after transverse aortic constriction (TAC) and the treatment was continued for 4 weeks. Pitavastatin significantly inhibited the progression from LV hypertrophy to heart failure as assessed on echocardiography. The cardiomyocyte cross-sectional area was significantly increased in the control group compared to the sham-operated mice (sham group), but it was not significantly different between the control group and the pitava group at 6 weeks after TAC. Moreover, pitavastatin induced myocardial angiogenesis (ratio of number of endothelial cells to cardiomyocytes) and decreased the myocardial fibrosis and oxidative stress. The expression of angiopoietin-1 in the heart was significantly increased by pitavastatin at 6 weeks after TAC.

CONCLUSIONS:

Pitavastatin has preventive effects on the progression of heart failure even in the hypertrophied heart.

• Authors: Yoshihito Kameda, Hiroshi Hasegawa, Akihiko Kubota, Hiroyuki Tadokoro, Yoshio Kobayashi, Issei Komuro, Hiroyuki Takano
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 76 Issue 5 Pg. 1159-68 ( 2012) ISSN: 1347-4820 [Electronic] Japan
• PMID: 22361916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiopoietin-1
• Angpt1 protein, mouse
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Quinolines
• pitavastatin

Topics

• Angiopoietin-1 (biosynthesis)
• Animals
• Blood Pressure
• Fibrosis (etiology, metabolism, pathology, prevention & control)
• Gene Expression Regulation (drug effects)
• Heart Failure (etiology, metabolism, pathology, prevention & control)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Hypertrophy, Left Ventricular (complications, metabolism, pathology)
• Mice
• Myocardium (metabolism, pathology)
• Neovascularization, Pathologic (metabolism, pathology, prevention & control)
• Oxidative Stress (drug effects)
• Quinolines (pharmacokinetics)
• Time Factors