Composição da lipoproteína de densidade alta (HDL) e sua capacidade em remover colesterol celular estão associadas ao risco reduzido de desenvolvimento de artrite reumatoide

Abstract

In rheumatoid arthritis (RA), the risk of cardiovascular death is 50% higher compared to the general population. This increased risk is partly due to the systemic inflammation characteristic of RA and changes in the lipoprotein profiles. This study investigated plasma lipid levels, lipid ratios, and the composition and functionality of high-density lipoprotein (HDL) in control individuals and RA subjects based on the disease’s inflammatory score (DAS28). HDL was isolated from fasting plasma by ultracentrifugation from individuals with RA (n=56) and control individuals (n=50) matched by age, sex and body mass index (BMI). Of the 56 participants with RA, 13 (23%) were in remission/low disease activity and 43 (77%) had active disease. Plasma lipids (total cholesterol, TC; triglycerides, TG) and HDL composition (TC; TG; phospholipids, PL) were determined using enzymatic methods; apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1), by immunoturbidimetry. Macrophages differentiated from cells obtained from the bone marrow of mice were loaded with cholesterol and then exposed to HDL from individuals in the RA and control groups for 24 h. After washing, the cells were incubated with lipopolysaccharides (LPS), as an inflammatory insult, for 24 h. The concentration of interleukin-6 (IL-6) and tumor necrosis factor (TNF) was determined in the culture medium by ELISA. Cellular cholesterol removal by HDL was determined in macrophages previously overloaded with cholesterol and 14C-cholesterol. Comparisons were made using the Mann–Whitney test, and binary logistic regression was used to identify the predictors of active RA. A p-value < 0.05 was considered significant. Plasma concentrations of low-density lipoprotein (LDLc), apoB and TG, and TG/HDLc were similar between the RA and CTR groups. Higher plasma concentrations of TC and HDLc, TC/apoB, and higher content of PL and apoA-1 in HDL were observed in total RA group. Subjects with active disease exhibited higher levels of TG and the TG/HDLc ratio; and lower levels of HDLc, the TC/apoB ratio, and TC and apoA-1 content in HDL particles compared to those with remission/low-activity RA. Increased levels of HDLc [odds ratio (OR) 0.931, 95% CI = 0.882–0.984], TC/apoB (OR 0.314, 95% CI = 0.126–0.78), and HDL particle content in TC (OR 0.912, 95% CI = 0.853–0.976), PL (OR 0.973, 95% CI = 0.947–1.000), and apoA-1 (OR 0.932, 95% CI = 0.882–0.985) were associated with a decreased risk of active disease, but BMI (OR 1.169, 95% CI = 1.004–1.360) and TG (OR 1.031, 95% CI = 1.005–1.057) were positively associated with active disease. There was no difference in IL-6 and TNF concentrations between the groups. A reduction in HDL-mediated cholesterol efflux increased the OR for active RA by 26.2%. The plasma levels of HDLc, along with the composition and functionality of HDL, influence the inflammatory score in RA and may affect the development of cardiovascular disease.