Immunogenetics of Atherosclerosis-Link between Lipids, Immunity, and Genes

Atherosclerosis is a complex disease process with lipid as a traditional modifiable risk factor and therapeutic target in treating atherosclerotic cardiovascular disease (ACVD). Recent evidence indicates that genetic influence and host immune response also are vital in this process. How these elements interact and modify each other and if immune response may emerge as a novel modifiable target remain poorly understood.

Numerous preclinical studies have clearly demonstrated that hypercholesterolemia is essential for atherogenesis, but genetic variations and host immune-inflammatory responses can modulate the pro-atherogenic effect of elevated LDL-C. Clinical studies also suggest that a similar paradigm may also be operational in atherogenesis in humans. More importantly each element modifies the biological behavior of the other two elements, forming a triangular relationship among the three. Modulating any one of them will have downstream impact on atherosclerosis. This brief review summarizes the relationship among lipids, genes, and immunity in atherogenesis and presents evidence to show how these elements affect each other. Modulation of immune response, though in its infancy, has a potential to emerge as a novel clinical strategy in treating ACVD.