High-dose atorvastatin improves hypercholesterolemic coronary endothelial dysfunction without improving the...

Area of Science:

• Cardiovascular Research
• Pharmacology
• Molecular Biology

Background:

• 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have shown biphasic effects on myocardial angiogenesis.
• Endothelial function in coronary disease can be restored by statins.
• Investigating high-dose atorvastatin's impact on angiogenesis in chronic myocardial ischemia is crucial.

Purpose of the Study:

• To investigate the functional and molecular effects of high-dose atorvastatin on the endogenous angiogenic response.
• To assess atorvastatin's impact on myocardial angiogenesis in hypercholesterolemic swine with chronic ischemia.

Main Methods:

• Yucatan pigs were fed normal or high-cholesterol diets, with or without atorvastatin (3 mg/kg/day) for 13 weeks.
• Chronic ischemia was induced by ameroid constrictor placement.
• Microvessel relaxation, myocardial perfusion, and protein expression were assessed.

Main Results:

• High-cholesterol diet impaired microvessel relaxation, which atorvastatin normalized.
• Collateral-dependent myocardial perfusion was reduced in both cholesterol-fed groups.
• Atorvastatin increased Akt phosphorylation, decreased vascular endothelial growth factor, and increased endostatin expression.

Conclusions:

• Atorvastatin improved hypercholesterolemia-induced endothelial dysfunction but did not improve collateral-dependent perfusion.
• Increased endostatin and decreased vascular endothelial growth factor expression, alongside Akt activation, may explain the diminished angiogenic response.
• High-dose atorvastatin's effects on angiogenesis are complex and warrant further investigation.