The versatility of HDL: a crucial anti-inflammatory regulator

Low levels of plasma high-density lipoprotein (HDL) represent a major cardiovascular risk factor and therefore raising HDL has been proposed to positively affect patients with atherosclerotic heart disease. However, the current evidence that raising HDL per se will reduce atherosclerosis and thereby cardiovascular events still remains controversial.

In this review, we discuss the diverse anti-atherogenic and anti-inflammatory properties of HDL in the light of recent findings indicating that the quality rather than the mere quantity of HDL determines its beneficial effects against atherosclerosis. More specifically, we will focus on the conspicuous anti-inflammatory properties of HDL as this might contribute to the overall beneficial effects of HDL in diseased patients such as modulation of costimulatory/adhesion molecule expression, cytokine production and inhibition of the prototypical proinflammatory transcription factor NF-κB.

A range of clinical disorders share permanent inflammation as a characteristic hallmark including coronary artery disease, chronic kidney disease, diabetes mellitus or rheumatoid arthritis and also display distinct qualitative changes in the HDL compartment. Loss of anti-inflammatory functions of HDL is emerging as an important risk factor for disease progression and survival in these clinical entities.

It will be important to define the anti-inflammatory effects of HDL at the molecular level and to dissect the manifold functional implications to develop both novel functional assays that enable meaningful outcome studies and foster new therapeutic concepts in patients with altered HDL function.