Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

Abstract

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes. KeywordsCerebral small vessel disease, endothelium, inflammation, lacunar infarcts, white-mater hyperintensities The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain.1 Age/hypertension-related SVDs and cerebral amyloid angiopathy are the most common sporadic forms of SVD. Among a few genetic forms of SVD, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), caused by NOTCH3 gene mutations, is the most frequent one. It is a systemic arteriopathy although the clinical symptoms are those caused by brain dysfunction. The effects of both sporadic and inherited SVD on the brain parenchyma are represented by lesions mainly located in the subcortical structures, and include lacunar infarcts, ischemic white-matter lesions, and intracerebral hemorrhage. An international working group has recently published the STRIVE (STandards for ReportIng Vascular changes on nEuroimaging) to provide definitions and imaging standards for markers and consequences of SVD.2 According to this consensus, changes currently seen on neuroimaging related to SVD include lacunes, recent small subcortical infarcts, white-matter hyperintensities (WMH), perivascular spaces (PVS), microbleeds (MB), and brain atrophy.Over the last few decades, evidence has being accumulated regarding prevalence, clinical significance, and

Leukoaraiosis, Cerebral Hemorrhage, and Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke

“…Rather than causing sICH and poor outcome directly, leukoaraiosis could be considered a marker of brain frailty and a chronic microvascular disease state, likely interacting with other risk factors to lower the threshold for the adverse outcomes. For example, small vessel disease is associated with endothelial dysfunction, 20 which in relation to matrix metalloproteinase cascade upregulation, disruption of the blood brain barrier, hyperglycemia and hypertension in the acute stroke setting, 21, 22 might modify the cerebral tissue response to IV thrombolysis. This hypothesis is also supported by the findings of a similar risk of bleeding and poor outcome after thrombolysis in association with cerebral microbleeds on pre-treatment MRI, another marker of severely diseased small cerebral vasculature.…”

Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response

“…Vascular inflammation has been linked to endothelial dysfunction 26 . However, we found no evidence of upregulation of inflammatory enzymes (NOX-2, MMPs or COX-2), adhesion molecules (ICAM, VCAM, etc.)…”

Atrial Fibrillation and Cognition

“…32 In this context, the assessment of circulating endothelial biomarkers has been proposed as a useful way for a better comprehension of the pathophysiology of SVD. 33 A direct link between AF and cerebral SVD has been rarely investigated, although, when attempted, some association have been found. 34 Last, but not least, AF and dementia share common risk factors, and these same risk factors seem to play an important role in by guest on May 11, 2018 http://stroke.ahajournals.org/ Downloaded from the progression of cognitive impairment, from mild cognitive impairment to dementia.…”