Psoriasis alters HDL composition and cholesterol efflux capacity

Abstract

This article is available online at http://www.jlr.org more than the skin ( 1 ). Traditional cardiovascular risk factors, such as hypertension, dyslipidemia, and obesity, are more frequent in psoriatic patients ( 2-4 ). However, even after adjusting for these risk factors, psoriasis has been shown to be associated with a higher incidence of myocardial infarction, stroke, and cardiovascular mortality ( 3,5,6 ). In moderate to severe psoriasis, a signifi cantly deteriorated lipid profi le was observed compared with healthy controls, with higher values of low-density lipoprotein, triglycerides, and signifi cantly decreased HDL levels ( 7 ).Recent studies clearly demonstrated that infl ammation impairs reverse cholesterol transfer in vivo ( 8, 9 ), providing evidence that infl ammation impairs HDL function. Emerging evidence suggests that assessment of HDL plasma concentrations alone is insuffi cient and indicate that the quality, rather than the mere quantity, of HDL determines its potential benefi cial effects against atherosclerosis ( 10 ). HDL is a complex lipoprotein particle with a broad variety of functions, also exerting atheroprotective activity via effects on the endothelium and by potent antiinfl ammatory capabilities ( 11-13 ). Recent studies have identifi ed HDL-associated proteins to be involved in the regulation of lipid metabolism, complement activation, growth-factor secretion, and proteolysis (14)(15)(16)(17)(18)(19).Functional impairment of HDL may contribute to the increased cardiovascular mortality experienced by psoriatic patients, but the impact of psoriasis on the composition and function of HDL has not been assessed. As qualitative alterations of HDL seem to be linked with increased cardiovascular complications, we hypothesized that HDL from psoriatic patients displays altered protein cargo and lipid composition, thereby rendering HDL dysfunctional.Abstract Psoriasis, a chronic infl ammatory skin disease, has been linked to increased myocardial infarction and stroke. Functional impairment of HDL may contribute to the excess cardiovascular mortality of psoriatic patients. However, data available regarding the impact of psoriasis on HDL composition and function are limited. HDL from psoriasis patients and healthy controls was isolated by ultracentrifugation and shotgun proteomics, and biochemical methods were used to monitor changed HDL composition. We observed a signifi cant reduction in apoA-I levels of HDL from psoriatic patients, whereas levels of apoA-II and proteins involved in acute-phase response, immune response, and endopeptidase/protease inhibition were increased. Psoriatic HDL contained reduced phospholipid and cholesterol. With regard to function, these compositional alterations impaired the ability of psoriatic HDL to promote cholesterol effl ux from macrophages. Importantly, HDLcholesterol effl ux capability negatively correlated with psoriasis area and severity index. We observed that control HDL, as well as psoriatic HDL, inhibited dihydrorhodamine (DHR) oxidation to a similar...

Unraveling the complexities of the HDL lipidome

“…Similarly, HDL free cholesterol is elevated in genetic LCAT defi ciency ( 108 ). By contrast, HDL content of cholesterol can be reduced in patients with psoriasis ( 92 ).…”

“…Furthermore, HDL3 from patients with myocardial infarction is enriched in triglyceride ( 95 ). Similarly, HDL from patients with malaria ( 117 ) and uremic patients on hemodialysis ( 91 ) displays elevated content of triglyceride, whereas HDL from patients with psoriasis is depleted in cholesteryl ester ( 92 ). Cytokine-induced increase in the activity of CETP paralleled by decreases in the activities of hepatic lipase, LPL, and LCAT can underlie hypertriglyceridemia, altered phospholipid composition characterized by elevated content of LPC and PE and diminished content of PC ( 90 ).…”

The Changing Face of HDL and the Best Way to Measure It

“…PON1 activity is substantially lower in patients with CAD, ACS, CKD, and RA, whereas lipoprotein-associated phospholipase A 2 (LpPLA 2 ) activity is increased in CKD and psoriasis (89,137,160,165,(171)(172)(173)(174)(175). Dysregulating the activity of PON1 and LpPLA 2 in this fashion not only compromises the antioxidative activity of HDL, but also promotes the formation of atherosclerotic plaques.…”

“…HDL fractions containing lower levels of apoA-I are observed in CKD, RA, and psoriasis, with SAA replacing apoA-I on HDL particles under inflammatory conditions (137,138,(165)(166)(167)(168). Patients with psoriasis have decreased apoA-I and apoM and increased apoA-II and SAA levels (169 ).…”

Epidemiology: Disease Associations and Modulators of HDL-Related Biomarkers

“…Recent reports have shown that HDL-C may be a biomarker for diseases like psoriasis (Holzer et al 2012), rheumatoid arthritis (Raterman et al 2013), and liver fibrosis in hepatitis C patients (Gangadharan et al 2012). Alterations in HDL composition have been observed also in hemodialysis patients (Mangé et al 2012).…”