LOX-1 variants modulate the severity of cardiovascular disease: state of the art and future directions

Area of Science:

• Cardiovascular Science
• Genetics
• Molecular Biology

Background:

• Atherosclerosis remains a leading cause of ischemic cardiovascular diseases, with many patients at high risk despite lipid-lowering therapy.
• Lectin-like oxidized LDL receptor-1 (LOX-1) plays a crucial role in atherogenesis by internalizing oxidized low-density lipoproteins.
• Factors like cytokines and shear stress can increase LOX-1 expression, contributing to disease progression.

Purpose of the Study:

• To review the current understanding of single-nucleotide polymorphisms (SNPs) affecting OLR1 splicing and LOX-1 function.
• To explore how genetic variants of OLR1 influence the severity of atherosclerosis and cardiovascular disease.
• To highlight the potential of OLR1 variants in developing novel preventive strategies and identifying high-risk individuals.

Main Methods:

• Review of existing literature on OLR1 gene, its isoforms, and associated SNPs.
• Analysis of studies linking OLR1 variants to atherosclerosis and cardiovascular disease outcomes.
• Examination of the functional impact of different OLR1 isoforms, such as LOXIN, on disease progression.

Main Results:

• The OLR1 gene exhibits various isoforms and SNPs that modulate LOX-1 activity and its role in atherosclerosis.
• Specific OLR1 variants, including 3'UTR polymorphisms, are associated with more severe forms of cardiovascular disease.
• The LOXIN isoform, lacking part of the functional domain, appears to offer protection against atherosclerosis.

Conclusions:

• Understanding OLR1 genetic variants is crucial for advancing atherosclerosis research beyond traditional lipid targets.
• Identification of specific OLR1 SNPs can aid in stratifying patients based on cardiovascular event risk.
• Targeting OLR1 pathways or utilizing genetic information may lead to personalized preventive therapies for cardiovascular diseases.