Research progress on the effect of hypercholesterolemia on neural function and cerebrovascular disease

Abstract

Cholesterol is an essential component for neural physiology. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood⁃brain barrier (BBB). In order to keep brain function well, the content of cholesterol in brain must be accurately maintained through close coordination between astrocyte, neurons and vascular endothelial cell, which are the three main components of neurovascular unit (NVU). Hypercholesterolemia is usually accompanied with increased permeability of BBB, activated astrocytes then upregulate the transcription of a series of cholesterol⁃related genes, leading to high expression of cholesterol transmembrane proteins, which destroy the stability of the cell⁃to⁃cell signal transduction between astrocyte and neuron, together with activated microglia releasing a large number of neuroinflammatory factors, triggering the neuroinflammatory response, and eventually lead to neuronal cell apoptosis. As a result, hypercholesterolemia related cognitive dysfunction is present. Vascular endothelial injury characterized by erythrocyte stasis, is an early manifestation of hypercholesterolemia on brain small vessels and capillaries, the appearance of fribi thrombi is a sign of the late stage of cerebral small vessel disease (CSVD), causing extensive occlusion of brain microvessels, resulting in decreased vascular density and cerebral blood flow. Hypercholesterolemia shows positive correlation with the characteristic features of CSVD on MRI, such as lacunar infarction, periventricular white matter hyperintensity and brain atrophy, but rarely with cerebral microbleeds (CMBs). With the advent of statins and their wide⁃spread application, the risk of stroke and its all⁃cause mortality decreased greatly around the world, which is mainly related to the significant decrease of plasma low density lipoprotein cholesterol (LDL⁃C) level caused by statins. However, there are still a number of controversial reports about the relationship with hypercholesterolemia, statin therapy and the risk of cerebral hemorrhage, thus, further work is needed.

doi：10.3969/j.issn.1672⁃6731.2021.02.008