Endothelial Dysfunction and Hyperhomocysteinemia-Linked Cerebral Small Vessel Disease: Underlying Mechanisms and Treatment Timing.

Shuang Li,Xia Luo,Jinglun Li,Lan Wen,Guangjian Li,Yan Huang

doi:10.3389/fneur.2021.736309

Abstract

Cerebral small vessel disease (cSVD)—a common cause of stroke and vascular dementia—is a group of clinical syndromes that affects the brain's small vessels, including arterioles, capillaries, and venules. Its pathogenesis is not fully understood, and effective treatments are limited. Increasing evidence indicates that an elevated total serum homocysteine level is directly and indirectly associated with cSVD, and endothelial dysfunction plays an active role in this association. Hyperhomocysteinemia affects endothelial function through oxidative stress, inflammatory pathways, and epigenetic alterations at an early stage, even before the onset of small vessel injuries and the disease. Therefore, hyperhomocysteinemia is potentially an important therapeutic target for cSVD. However, decreasing the homocysteine level is not sufficiently effective, possibly due to delayed treatment, which underlying reason remains unclear. In this review, we examined endothelial dysfunction to understand the close relationship between hyperhomocysteinemia and cSVD and identify the optimal timing for the therapy.

Highlights

Cerebral small vessel disease refers to a series of clinical, imaging, and pathological syndromes caused by various etiological factors affecting small arteries, capillaries, and venules in the brain
Several studies have shown that interventions to reduce tHcy, such as Bvitamin supplementation alone or in combination, had no effect on myocardial infarction and death from any cause or adverse event; statistical differences were observed in the stroke group [33, 34]. These results suggested that the nervous system may be more sensitive to the toxic effects of HHcy than the cardiovascular system
Nam et al showed that if an ischemic stroke occurs in Cerebral small vessel disease (cSVD) patients, disease progression might not be reversed by treatments meant to lower the tHcy levels, which suggest that patients with early or preclinical cSVD are more likely to benefit from Hcy-lowering therapy, and the curative effect was closely related to the timing of the treatment [68]

Summary

Introduction

Cerebral small vessel disease (cSVD) refers to a series of clinical, imaging, and pathological syndromes caused by various etiological factors affecting small arteries, capillaries, and venules in the brain. Abnormal endothelial secretion of soluble ICAM-1, promotes the adhesion of leucocytes, which causes small vessels to occlude, and leads to incidence of silent brain infarctions and periventricular white matter lesions, implying ED in relation to progression of ischemic cerebral small vessel disease in type 2 diabetes [52].

Results

Conclusion