Hepatic pseudocapillarisation and atherosclerosis in ageing

Area of Science:

• Gerontology
• Vascular Biology
• Hepatology

Background:

• Cardiovascular disease (CVD) is a leading cause of death, with aging as a primary risk factor.
• Atherosclerosis underlies much of this age-related CVD.
• Current understanding lacks a direct link between liver aging and atherosclerosis pathogenesis.

Purpose of the Study:

• To propose a novel hypothesis linking age-related liver structural changes to atherosclerosis.
• To elucidate the role of liver sinusoidal endothelium fenestrations in this process.

Main Methods:

• Review and synthesis of existing literature on liver aging and atherosclerosis.
• Hypothetical model development based on established pathogenic mechanisms.

Main Results:

• Age-related pseudocapillarisation of liver sinusoidal endothelium involves endothelial thickening, basement membrane formation, and fenestration loss (defenestration).
• This defenestration impairs the liver sieve function, hindering chylomicron remnant clearance.
• Impaired clearance leads to postprandial hypertriglyceridaemia, a known contributor to atherosclerosis.

Conclusions:

• Age-induced loss of liver fenestrations directly contributes to atherosclerosis development.
• Maintaining or restoring liver fenestrations may offer a new therapeutic strategy for age-related CVD.
• Targeting liver sieve permeability could mitigate cardiovascular risk in the elderly.