Angiogenic Markers in Cerebrovascular Disease (ANFIS)

Plain-language summary

Intracranial atherosclerosis (ICAS) is the most common cause of stroke worldwide. It carries a worse prognosis than other stroke etiologies, with an annual rate of recurrent stroke and death of 15% despite intensive medical management, and as high as 35% in certain populations. Overall, treatment and prevention of stroke due to ICAS has been unsuccessful. While two recent clinical trials have shown modest improvement in the efficacy of intensive medical treatment, these trials were terminated early given the elevated rate of complications, stroke, and death in the interventional arms. In fact, intensive medical management appears to reduce the risk of embolism; however, medical management alone does not address the progression of intracranial arterial stenosis or the pathophysiologic components of hypoperfusion and poor collateral circulation. Levels and types of various angiogenic factors in the blood and tissues have been proposed to be predictive of patient outcome after ischemic stroke and treatment for stroke. This study therefore pursues a new paradigm to investigate responses to ICAS treatment from the perspective of cerebral collateral vessel generation and the role of angiogenic factors. Specifically, pro- and anti-angiogenic factors in patients with ICAS are evaluated at baseline and longitudinally in response to both medical and surgical treatment. For this we have developed methodologies for the isolation and measurement of these growth factors in plasma of patients with ICAS. These methodologies will enable us to obtain a detailed understanding of the variation and dynamic properties of local and circulating angiogenic factors over time in response to medical and surgical treatment, and their association to outcome phenotypes. This analysis is complemented by studies of angiographic development of neovascularization. If successful, this study will help to better understand the role of angiogenesis in ICAS and create a foundation from which to explore therapeutic treatments for ICAS which harness the natural processes of angiogenesis.

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