Loading...
Please wait, while we are loading the content...
Similar Documents
Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Endres, Matthias Laufs, Ulrich Huang, Zhihong Nakamura, Teruya Huang, Paul Lee Moskowitz, Michael A. Liao, James K. |
| Copyright Year | 1998 |
| Abstract | The treatment of ischemic strokes is limited to prophylactic agents that block the coagulation cascade. Here, we show that cholesterol-lowering agents, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, protect against cerebral injury by a previously unidentified mechanism involving the selective up-regulation of endothelial NO synthase (eNOS). Prophylactic treatment with HMG-CoA reductase inhibitors augments cerebral blood flow, reduces cerebral infarct size, and improves neurological function in normocholesterolemic mice. The up-regulation of eNOS by HMG-CoA reductase inhibitors is not associated with changes in serum cholesterol levels, but is reversed by cotreatment with L-mevalonate and by the downstream isoprenoid, geranylgeranyl pyrophosphate and not by farnesyl pyrophosphate. The blood flow and neuroprotective effects of HMG-CoA reductase inhibitors are completely absent in eNOS-deficient mice, indicating that enhanced eNOS activity by HMG-CoA reductase inhibitors is the predominant if not the only mechanism by which these agents protect against cerebral injury. Our results suggest that HMG-CoA reductase inhibitors provide a prophylactic treatment strategy for increasing blood flow and reducing brain injury during cerebral ischemia. |
| Starting Page | 32 |
| Ending Page | 40 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/95/15/8880.full.pdf |
| PubMed reference number | 9671773v1 |
| Volume Number | 95 |
| Issue Number | 15 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 3-hydroxy-3-methylglutaryl-coenzyme A Blood Coagulation Disorders Brain Injuries Cerebral Infarction Cerebral Ischemia Cerebrovascular Circulation Cerebrovascular accident Cholesterol Combined Modality Therapy Condoms, Unspecified Hydroxymethylglutaryl coenzyme A reductase Hydroxymethylglutaryl-CoA Reductase Inhibitors Ischemic stroke Isoprenoids Mevalonate NOS3 protein, human Nervous System Physiological Phenomena Nitric Oxide Synthase Technetium TC-99M Pyrophosphate Up-Regulation (Physiology) |
| Content Type | Text |
| Resource Type | Article |
