Epidemiological studies have shown an inverse relationship between severely low HDL-cholesterol levels and CHD. Besides the capacity in promoting cholesterol efflux, HDL can contribute to atheroprotection through a role in the modulation of the immune response. Among immune cells, monocytes can contribute in creating a pro-inflammatory milieu that supports the atherosclerotic process. In this study we aim to evaluate the effect of genetic HDL deficiency, specifically determined by mutations in LCAT gene, on monocyte immunophenotype and function.  
Monocytes were isolated from fresh blood in carriers of LCAT mutations (n=12) and from controls (n=9) matched for age, sex and BMI. Ex vivo analysis was performed with fluorescence-activated cell sorter analysis, inflammatory stimulation and transendothelial migration assays.
While no difference in the monocyte subset distribution was found between carriers and controls, expression of the integrin CD11c was nearly half in mutant LCAT (ΔMFI 220±56 vs 415±38 P=0.042) and monocytes displayed a reduction in migratory capacity compared to control (39.7±1.92 vs 48.0±1.83 %of migrated monocytes P=0.006). Monocytes from carriers proved to be less efficient in producing IL-8 and IL-1β upon 24-hour stimulation with LPS and Pam3Cys, and shown a decreased production of MCP-1 at baseline. All the effects were gene-dose dependent. No difference in circulating levels of hsCRP, MCP-1, TNF-α and IL-6 was appreciated. 
Genetic HDL deficiency due to LCAT gene mutations is associated with a dampened immune response of monocytes, despite the low plasma HDL-C levels. These findings contribute to our understanding of the increased atheroprotective role of HDL often seen in this disease.

01 - LOW HDL-CHOLESTEROL LEVELS ARE ASSOCIATED WITH A DECREASED MONOCYTE ACTIVITY AND INFLAMMATION IN CARRIERS OF LCAT MUTATION