HDL – Immune Cell Crosstalk in Autoimmune Diseases and its Role in Accelerated Atherosclerosis

Despite remarkable advances in lipid-lowering therapies, atherosclerotic cardiovascular disease (ASCVD) continues to be a major cause of morbidity and mortality worldwide, and chronic inflammation has been shown to contribute to residual cardiovascular risk.Autoimmune diseases are increasingly recognized as being associated with an increased risk of ASCVD that cannot be explained by traditional cardiovascular risk factors, such as dyslipidemia and hypertension.High-density lipoprotein (HDL) is an anti-atherogenic lipoprotein involved in reverse cholesterol transport. Recent studies have demonstrated that HDL possesses anti-inflammatory and immunomodulatory properties. In autoimmune diseases, both HDL dysfunction and immune dysregulation have been reported, including an impaired cholesterol efflux capacity (CEC), reduced paraoxonase-1 activity, alterations in HDL particle composition, and serum amyloid A enrichment. These findings suggest that crosstalk between HDL and immune cells may play an important role in atherosclerosis progression.Accordingly, this review summarizes the current evidence on HDL-immune cell interactions, discusses how HDL dysfunction contributes to accelerated atherosclerosis in autoimmune diseases, and highlights the therapeutic potential of targeting the HDL function to reduce residual cardiovascular risk or ASCVD risk.