Endothelial Activation in Lacunar Stroke Subtypes

Knottnerus, Iris L.H.; Govers‐Riemslag, José W. P.; Hamulyák, Karly; Rouhl, Rob P.W.; Staals, Julie; Spronk, Henri M. H.; Oerle, René van; Raak, E.P.M. van; Lodder, J.; Cate, Hugo Ten; Oostenbrugge, Robert J. van

doi:10.1161/strokeaha.109.576223

Cited by 66 publications

(55 citation statements)

References 36 publications

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“…Very few studies used cellular biomarkers of endothelial dysfunction. Finally, with the exception of a few studies, 52,66,74,79,84 only selective biomarkers involved in different points of the complex pathways linking together endothelial dysfunction and coagulation system/inflammation processes were analyzed. It should be underlined that the assessment of individual biomarkers cannot provide information on relative contributions by the distinct pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Plasminogen activator inhibitor resulted independently associated with the presence of WMH and/or lacunar infarcts and reduced fractional anisotropy on diffusion tensor imaging sequences in three studies. 71,74,79 Four studies investigated the association between D-dimer and markers of SVD. Gottesmann et al 52 found an independent association between D-dimer levels and subclinical lacunar infarcts in the Atherosclerosis Risk in Communities cohort.…”

Section: 61mentioning

confidence: 99%

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

Poggesi

Pasi

Pescini

et al. 2015

J Cereb Blood Flow Metab

220

183

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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

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Section: Discussionmentioning

confidence: 99%

Section: 61mentioning

confidence: 99%

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

Poggesi

Pasi

Pescini

et al. 2015

J Cereb Blood Flow Metab

220

183

View full text Add to dashboard Cite

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“…26 Blood pressure is the major determinant of arteriosclerosis and endothelial dysfunction in patients with chronic kidney disease, 27 and endothelial dysfunction within capillaries appears to contribute to the development of CMBs. 28 Recent studies have shown that endothelial dysfunction is an important mechanism of cerebrovascular damage in patients with lacunar infarction 29 that is correlated with an increased risk of acute ischemic stroke. 30 However, the exact mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis

et al. 2012

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Cerebral microbleeds (CMBs) are recognized as a manifestation of arteriolosclerosis in cerebral small vessels. However, little is known regarding whether stroke patients with CMBs often have systemic atherosclerosis. The aim of the present study was to elucidate this issue using the cardio-ankle vascular index (CAVI), a new index of systemic atherosclerosis, in acute ischemic stroke patients. We prospectively studied 105 patients (71 males, median age ¼ 70.0 years) with acute ischemic stroke. All of the patients were examined using T2*-weighted gradient echo magnetic resonance imaging (MRI) to look for and assess the CMBs and using fluid-attenuated inversion recovery to evaluate white matter hyperintensity (WMH). We assigned the patients into CMB and non-CMB groups and compared the clinical characteristics of these groups. The factors associated with CMBs were investigated using multivariate logistic regression analysis. T2*-weighted gradient echo MRI revealed CMBs in 47 patients (44.8%) and no CMBs in 58 patients (55.2%). The CAVI was significantly higher in the CMBs group (10.5 vs. 8.6, Po0.001).In the multivariate logistic regression analysis, CAVI per one point increase (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.12-2.00; P ¼ 0.006), advanced WMH (OR, 4.78; 95% CI, 1.55-14.74; P ¼ 0.006) and impaired kidney function (OR, 3.31; 95% CI, 1.16-9.81; P ¼ 0.031) were independent factors associated with the presence of CMBs. A high CAVI was independently associated with CMBs in patients with acute ischemic stroke. Our results indicated that ischemic stroke patients with CMBs may have cerebral arteriolosclerosis as well as systemic atherosclerosis.

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“…37 An intact vascular endothelium is also required for effective autoregulation of cerebral blood flow. In a study monitoring circulating blood markers in lacunar stroke, Knottnerus et al 38 concluded that endothelial dysfunction is a significant mechanism confined to the asymptomatic but not to the symptomatic subtype.…”

Section: Factors That Increase Vulnerability To Sbimentioning

confidence: 99%

“…В исследовании по монито-рингу циркулирующих в крови маркеров лакунарного инсульта Knottnerus и соавт. [38] пришли к выводу, что дисфункция эндотелия является важным механизмом, характерным для бессимптомного, но не симптомного подтипа.…”

Section: Disclosuresunclassified