Abnormal lipoprotein particles and cholesterol efflux capacity in patients with psoriasis

Abstract

Objectives Psoriasis is a Th-1/17 mediated inflammatory disease associated with increased risk of cardiovascular disease (CVD). Inflammation may modulate lipoprotein particle number and directly impair HDL functions, in particular reverse cholesterol transport (RCT). We sought to study how chronic in vivo inflammation modulates lipoprotein particle composition using nuclear magnetic resonance spectroscopy (NMR) and HDL efflux in psoriasis. Methods and Results We prospectively enrolled a consecutive sample of patients with psoriasis (n=122) and compared lipoprotein and metabolic risk factors to patients without psoriasis (n=134). Fasting lipids, insulin, glucose were measured by standard assays, and lipoprotein concentration and size were measured by NMR. In a random subset (n=100 each group), HDL efflux capacity was quantified using a validated ex vivo system involving the incubation of macrophages with apolipoprotein B-depleted serum from patients. Traditional lipid concentrations were similar in both groups except for HDL concentration which was lower in psoriasis (43 mg/dL (36–58) vs 50 (42–62), p<0.01). However, NMR showed an atherogenic profile in psoriasis similar to that observed in diabetes, with significant increase in LDL particle concentration [1210.5 (1002–1498) vs 1115 (935–1291), p=0.03] with decrease in LDL size [20.6 (20.3–21.1) vs 21.3 (20.6–21.1), p<0.001] beyond CV risk factors and HOMA-IR (p=0.001). Finally, HDL efflux capacity was lower in psoriasis compared to controls in fully adjusted models (beta −0.14, p=0.001). Conclusions These data support a more atherogenic lipoprotein profile by NMR and decreased HDL efflux capacity in psoriasis patients compared to controls beyond CVD risk factors. The abnormal lipoprotein particle composition and HDL efflux capacity in psoriasis may provide a link between psoriasis and CVD.

Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

“…Analysis of the plasma lipid showed a decrease in total cholesterol, cholesterol esters, and phospholipids (Supplemental Figure 2B). We also measured serum cholesterol efflux capacity, which is the ability of HDL to accept lipids for reverse cholesterol transport; this has been shown to be impaired in psoriasis patients (20) and accelerate atherosclerosis in humans (21). We found HDL efflux to be significantly decreased by 20% in the K14-Rac1V12 -/+ mice (Supplemental Figure 2C).…”

IL-22 is induced by S100/calgranulin and impairs cholesterol efflux in macrophages by downregulating ABCG1

“…This is supported by the in vitro experiments demonstrating that rIL-22 downregulates ABCG1 expression in THP-1 macrophages and is functionally validated by reduced cholesterol effl ux. Mehta et al ( 49 ) recently reported on reduced cholesterol effl ux capacity of serum from patients with psoriasis. Although the IL-22 level was not reported in this cohort study, our data raises the hypothesis that elevated IL-22 levels often associated with autoimmune diseases, including psoriasis and rheumatoid arthritis, may mediate reduced cholesterol effl ux in foam cells.…”

The Association Between Psoriasis and Cardiovascular Diseases

“…Increased levels of total cholesterol, triglycerides, lowdensity lipoprotein cholesterol, oxidatively modified lipids, and decreased levels of HDL(açılımını yaz) cholesterol is exhibited by patients with psoriasis by numerous studies (40,46). Mehta et also supportted that a more atherogenic lipoprotein profile and decreased HDL efflux capacity in psoriasis patients compared to controls beyond CVD risk factors.…”

“…Mehta et also supportted that a more atherogenic lipoprotein profile and decreased HDL efflux capacity in psoriasis patients compared to controls beyond CVD risk factors. The abnormal lipoprotein particle composition and HDL efflux capacity in psoriasis may provide a link between psoriasis and CVD (46). Lipoprotein (a) (Lp(a)) is a genetically established molecule whose function has been involved in cardiovascular pathology, and whose levels have been accounted to be raised in patients with psoriasis may be a factor contributing to an increased cardiovascular risk in patients with psoriasis (47).…”