Endothelial Dysfunction in Lacunar Stroke: A Systematic Review

Abstract

Background: Endothelial dysfunction is thought to play an important role in the pathogenesis and progression of cerebral small-vessel disease in lacunar stroke patients. Methods: We systematically searched the literature (MEDLINE, EMBASE) for evidence of endothelial activation and dysfunction in lacunar stroke. The selected papers were assessed by a predefined checklist to estimate methodological and informative quality. The papers were categorized into subheadings concerning the different physiologic functions of the endothelium and a subheading concerning toxins for the endothelium. Results: 29 articles were eligible for further analysis. We found 16 publications on regulation of vascular tone by the endothelium, which showed an impaired function at several time points after the stroke by means of different clinical methods (e.g. flow-mediated vasodilatation and CO₂ reactivity). Nine references showed elevated levels of markers of hemostatic function of the vascular endothelium (e.g. von Willebrand factor, thrombomodulin) in acute and subsequent phases. In 4 papers, adhesion molecules (e.g. E- and P-selectin) were elevated only during the acute phase. Homocysteine, a toxin for the endothelium, was elevated in patients in 3 papers. Conclusions: The current literature suggests that endothelial dysfunction might be involved in the pathogenesis of lacunar stroke, especially in those patients with concomitant silent lacunar infarcts and ischemic white matter lesions. Future research on endothelial function in lacunar stroke should concentrate on long-term clinical as well as radiological follow-up in well-defined cases and combine multiple methods to evaluate endothelial function.

Extended extraocular phenotype of PROM1 mutation in kindreds with known autosomal dominant macular dystrophy

“…Interestingly, the presence of MPs has also been reported to be positively associated with contrast-enhancing lesions on brain MRI in subjects with multiple sclerosis 35 and furthermore, endothelial dysfunction is thought to have an important role in the pathogenesis of cerebral small-vessel disease especially in those patients with concomitant silent lacunar infarcts and ischaemic WM lesions. 36 In line with this possible accelerated aging effect, the older member from the kindred B and one carrier of the PROM1 mutation in family A showed some memory disturbance and impairment in measures of executive functions in addition to small WM lesions. The remaining carriers in both families had average IQs and unimpaired performance on the other cognitive measures.…”

Insulin Resistance Is a Risk Factor for Silent Lacunar Infarction

“…31 It is regarded that the activation of the cerebral microvascular endothelium might be the primary step in the pathogenesis of SLI, subsequently leading to increased permeability of the blood-brain barrier. 34,35 IR is also suggested to be related to endothelial dysfunction. Both IR and endothelial dysfunction are commonly observed in many cardiovascular diseases.…”

A Systematic Review of Dynamic Cerebral and Peripheral Endothelial Function in Lacunar Stroke Versus Controls

“…11 A recent systematic review identified endothelial dysfunction in lacunar ischemic stroke but did not control for risk factor exposure or other stroke subtypes. 12 Therefore, it is unclear whether endothelial changes observed in patients with lacunar ischemic stroke might be specific to small vessel disease or simply reflect age, vascular risk factors, generalized (possibly coincidental) atheroma, or the effects of having a stroke. We performed a systematic review of all studies that assessed cerebral or peripheral vascular reactivity in patients with lacunar ischemic stroke.…”