Correlation between serum soluble ASGR1 concentration and low-density lipoprotein cholesterol levels: a cross-sectional study

Abstract

Background: Recent studies have shown that loss-of-function mutations in hepatic asialoglycoprotein receptor 1 (ASGR1) are associated with low levels of circulating cholesterol and a reduced risk of coronary artery disease (CAD). In contrast to ASGR1 on the hepatocyte membrane, serum soluble ASGR1 (sASGR1) is a secreted form that has been detected in circulation. However, the functions of serum sASGR1 are unclear. This study aims to investigate the relationship between human serum sASGR1 concentration and low-density lipoprotein cholesterol (LDL-C) levels.

Methods: In a cohort of 134 participants who underwent coronary angiography examination, basic information was recorded, and blood samples were collected for biochemical testing. The serum sASGR1 concentration was determined by ELISA kits. The relationship between sASGR1 concentration and LDL-C levels was examined using linear regression models and interaction tests. Univariate and multivariate analyses were used to identify clinical variables that affect sASGR1 levels.

Results: After adjusting for potential confounders such as age, sex, BMI, and statin use, the serum sASGR1 concentration was positively correlated with LDL-C levels (β = 0.093, 95% CI: 0.04 to 0.14, P < 0.001). Subgroup analysis and interaction tests showed that the effect of serum sASGR1 concentration on LDL-C levels was significantly influenced by hypertension status (P for interaction = 0.0067). The results of a multivariate linear regression analysis incorporating age, serum TG, LDL-C, nonesterified fatty acid (NEFA), white blood cell counts (WBCC), and fibrinogen revealed that LDL-C (β = 1.005, 95% CI: 0.35 to 1.66, P = 0.003) and WBCC (β = 0.787, 95% CI: 0.41 to 1.16, P < 0.0001) were independent influencing factors for serum sASGR1 levels.

Conclusions: The serum sASGR1 concentration was positively correlated with LDL-C levels. In addition, hypertension status significantly affected the effect of serum sASGR1 on LDL-C levels. This study provides some research ideas for clinical doctors and researchers, as well as some references for additional research on serum sASGR1.

Keywords: ASGR1; Atherosclerotic cardiovascular disease; Cholesterol metabolism; Lipid metabolism; Low-density lipoprotein cholesterol.

Fig. 1

Relationship between serum sASGR1 and hASGR1. Circulating asialoglycoproteins bind hASGR1 on the surface of hepatocytes, ultimately resulting in reduced intracellular cholesterol efflux (red arrow). Circulating sASGR1 secreted by the liver competitively binds asialoglycoproteins with hASGR1. The sASGR1-asialoglycoprotein complex also enters the liver through hASGR1 on the surface of hepatocytes (black arrow)