Statins augment collateral growth in response to ischemia but they do not promote cancer and atherosclerosis.

Abstract

3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are widely prescribed to lower cholesterol. Recent reports suggest that statins may promote angiogenesis in ischemic tissues. It remains to be elucidated whether statins potentially enhance unfavorable angiogenesis associated with tumor and atherosclerosis. Here, we induced hind limb ischemia in wild-type mice by resecting the right femoral artery and subsequently inoculated cancer cells in the same animal. Cerivastatin enhanced blood flow recovery in the ischemic hind limb as determined by laser Doppler imaging, whereas tumor growth was significantly retarded. Cerivastatin did not affect capillary density in tumors. Cerivastatin, pitavastatin, and fluvastatin inhibited atherosclerotic lesion progression in apolipoprotein E-deficient mice, whereas they augmented blood flow recovery and capillary formation in ischemic hind limb. Low-dose statins were more effective than high-dose statins in both augmentation of collateral flow recovery and inhibition of atherosclerosis. These results suggest that statins may not promote the development of cancer and atherosclerosis at the doses that augment collateral flow growth in ischemic tissues.

• Authors: Masataka Sata, Hiroaki Nishimatsu, Jun-ichi Osuga, Kimie Tanaka, Nobukazu Ishizaka, Shun Ishibashi, Yasunobu Hirata, Ryozo Nagai
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 43 Issue 6 Pg. 1214-20 (Jun 2004) ISSN: 1524-4563 [Electronic] United States
• PMID: 15166180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Fatty Acids, Monounsaturated
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Indoles
• Pyridines
• Quinolines
• Fluvastatin
• cerivastatin
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Nos3 protein, mouse
• pitavastatin

Topics

• Animals
• Apolipoproteins E (deficiency, genetics)
• Arteriosclerosis (chemically induced, etiology, genetics)
• Fatty Acids, Monounsaturated (administration & dosage, pharmacology, therapeutic use)
• Femoral Artery (surgery)
• Fluvastatin
• Hindlimb (blood supply)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, pharmacology, therapeutic use, toxicity)
• Hypercholesterolemia (complications, genetics)
• Indoles (administration & dosage, pharmacology, therapeutic use)
• Ischemia (drug therapy, physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neovascularization, Pathologic (chemically induced)
• Neovascularization, Physiologic (drug effects)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Pyridines (administration & dosage, pharmacology, therapeutic use, toxicity)
• Quinolines (administration & dosage, pharmacology, therapeutic use)