Role of the vascular endothelium and plaque in acute ischemic stroke

The underlying cause of stroke lies in the damage to the arterial endothelial cell layer. The most profound damage is due to atherosclerosis, which can either occlude an artery or produce a thromboembolism. Diabetes and inflammation contribute to atherosclerosis and the associated endothelial damage by initiating and promoting the deposition of modified lipids in the subendothelium and by inhibiting endothelial nitric oxide (NO) production. At the same time, both production of endothelin-1 and generation of reactive oxygen species increase. In addition, leukocytes adhere to the endothelium and levels of C-reactive protein increase. The stroke that ensues upon cerebral artery occlusion or plaque rupture continues and exacerbates endothelial damage. Statins have been shown to be helpful in preventing stroke and diminishing its consequences. An international clinical trial to determine if an NO donor is effective (Efficacy of Nitric Oxide in Stroke study) is currently under way. Other interventions such as antioxidants, ρ kinase inhibition, and endothelial progenitor cells offer promising avenues of research and perhaps therapeutic avenues for treatment of stroke. This article discusses the role of the vascular endothelium in ischemic stroke and those interventions that may provide plausible avenues for future therapy.