Systemic lupus erythematosus and cardiovascular disease: prediction and potential for therapeutic intervention

Abstract

Patients with systemic lupus erythematosus have a significantly increased risk of cardiovascular events due to atherosclerosis. Traditional cardiac risk factors cannot fully explain this increased risk. Recent evidence strongly suggests that atherosclerotic plaque is largely driven by inflammation and an active immunological response, in contrast to the long-held belief that plaque is a passive accumulation of lipids in the arterial wall. Current approaches to the prevention of atherosclerosis in systemic lupus erythematosus involve targeting modifiable cardiac risk factors. Future preventive strategies may include therapies that counteract the immunologic responses that lead to plaque formation.

Figure 1. Effects of high-density lipoprotein and proinflammatory high-density lipoprotein on atherosclerosis initiation and progression

(A) Illustration of the interaction between LDL, the entrance of monocytes into the artery wall, formation of oxidized LDL (OxLDL), and the engulfment of OxLDL by macrophages to form foam cells. HDL interrupts this atherosclerotic process by reverse cholesterol transport of oxidized lipids from foam cells, by blocking endothelial cell activation, and by prevention of oxidation of LDL via antioxidative enzymes in the normal HDL particle such as paraoxonase. (B) Proinflammatory, pro-oxidant HDL cannot carry out many of the protective functions of normal functioning HDL, leading to the formation of OxLDL, the release of chemokines and cytokines, the engulfment of OxLDL by CD36 receptors on macrophages to form foam cells and ultimately atherosclerotic plaque. HDL: High-density lipoprotein; LDL: Low-density lipoprotein; MCP-1: Monocyte chemotactic protein-1; piHDL: Proinflammatory high-density lipoprotein; ROS: Reactive oxygen species.