Vascular dysfunction in cerebrovascular disease: mechanisms and therapeutic intervention

Miller, A. A. , Budzyn, K. and Sobey, C. G. (2010) Vascular dysfunction in cerebrovascular disease: mechanisms and therapeutic intervention. Clinical Science, 119(1), pp. 1-17. (doi: 10.1042/CS20090649) (PMID:20370718)

Abstract

The endothelium plays a crucial role in the control of vascular homoeostasis through maintaining the synthesis of the vasoprotective molecule NO• (nitric oxide). Endothelial dysfunction of cerebral blood vessels, manifested as diminished NO• bioavailability, is a common feature of several vascular-related diseases, including hypertension, hypercholesterolaemia, stroke, subarachnoid haemorrhage and Alzheimer's disease. Over the past several years an enormous amount of research has been devoted to understanding the mechanisms underlying endothelial dysfunction. As such, it has become apparent that, although the diseases associated with impaired NO• function are diverse, the underlying causes are similar. For example, compelling evidence indicates that oxidative stress might be an important mechanism of diminished NO• signalling in diverse models of cardiovascular ‘high-risk’ states and cerebrovascular disease. Although there are several sources of vascular ROS (reactive oxygen species), the enzyme NADPH oxidase is emerging as a strong candidate for the excessive ROS production that is thought to lead to vascular oxidative stress. The purpose of the present review is to outline some of the mechanisms thought to contribute to endothelial dysfunction in the cerebral vasculature during disease. More specifically, we will highlight current evidence for the involvement of ROS, inflammation, the RhoA/Rho-kinase pathway and amyloid β-peptides. In addition, we will discuss currently available therapies for improving endothelial function and highlight future therapeutic strategies.

• Item Type: Articles
• Additional Information: A.A.M. is the recipient of an NHMRC (National Health and Medical Research Council) Biomedical Career Development Award. K. B. is the recipient of an NHMRC C. J .Martin Training Fellowship. C.G. S. is an NHMRC a Senior Research Fellow.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Miller, Dr Alyson
• Authors: Miller, A. A., Budzyn, K., and Sobey, C. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Clinical Science
• Publisher: Portland Press
• ISSN: 0143-5221
• ISSN (Online): 1470-8736
• Published Online: 07 April 2010