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Abnormal lipoprotein particles and cholesterol efflux capacity in patients with psoriasis
Nehal N Mehta1, Ron Li, Parasuram Krishnamoorthy
1Cardiovascular Institute, University of Pennsylvania School of Medicine, USA. nehal.mehta@uphs.upenn.edu
Insights
Psoriasis patients exhibit an atherogenic lipoprotein profile and reduced HDL efflux capacity, suggesting a link between this inflammatory skin disease and cardiovascular disease (CVD) risk.
Area of Science:
- Cardiovascular disease research
- Dermatology
- Metabolic and inflammatory diseases
Background:
- Psoriasis is an inflammatory disease linked to increased cardiovascular disease (CVD) risk.
- Chronic inflammation in psoriasis may negatively impact lipoprotein metabolism and HDL function, including reverse cholesterol transport (RCT).
- Understanding these effects is crucial for managing CVD risk in psoriasis patients.
Purpose of the Study:
- To investigate how chronic inflammation in psoriasis affects lipoprotein particle composition.
- To assess HDL efflux capacity in patients with psoriasis compared to controls.
- To explore the relationship between psoriasis, lipoprotein abnormalities, and CVD risk factors.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyze lipoprotein particle concentration and size.
- HDL efflux capacity was quantified ex vivo using macrophages and patient serum.
- Lipoprotein and metabolic risk factors were compared between 122 psoriasis patients and 134 controls.
Main Results:
- Psoriasis patients showed a significantly higher LDL particle concentration and smaller LDL particle size compared to controls, indicative of an atherogenic profile.
- Despite similar traditional lipid levels (except lower HDL in psoriasis), NMR revealed distinct lipoprotein differences beyond traditional CVD risk factors and HOMA-IR.
- HDL efflux capacity was significantly lower in psoriasis patients, even after adjusting for other risk factors.
Conclusions:
- Psoriasis is associated with an atherogenic lipoprotein profile and impaired HDL efflux capacity.
- These lipoprotein abnormalities may contribute to the elevated CVD risk observed in psoriasis.
- The findings highlight potential mechanisms linking psoriasis-related inflammation to cardiovascular complications.
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 = 0.02] 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.
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