Upregulation of Type III endothelial cell Nitric Oxide Synthase by HMG-CoA reductase inhibitors

US6147109A · kind A · utility

Assignees

• The General Hospital Corporation · US
• The Brigham and Women's Hospital, Inc. · US

Inventors

• James Liao · Boston, US
• Ulrich Laufs · Cologne, DE
• Matthias Endres · Berlin, DE
• Michael A. Moskowitz · Belmont, US

Key dates

• Filing date: Aug 11, 1998
• Grant date: Nov 14, 2000
• Expiry date: Aug 11, 2018

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P43/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A new use for HMG-CoA reductase inhibitors is provided. In the instant invention, HMG-CoA reductase inhibitors are found to upregulate endothelial cell Nitric Oxide Synthase activity through a mechanism other than preventing the formation of oxidative-LDL. As a result, HMG-CoA reductase inhibitors are useful in treating or preventing conditions that result from the abnormally low expression and/or activity of endothelial cell Nitric Oxide Synthase. Such conditions include pulmonary hypertension, ischemic stroke, impotence, heart failure, hypoxia-induced conditions, insulin deficiency, progressive renal disease, gastric or esophageal motility syndrome, etc. Subjects thought to benefit mostly from such treatments include nonhyperlipidemics and nonhypercholesterolemics, but not necessarily exclude hyperlipidemics and hypercholesterolemics.