Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
Department of Dermatology, Medical University of Graz, Graz, Austria.
J Invest Dermatol. 2014 Mar;134(3):635-642. doi: 10.1038/jid.2013.359. Epub 2013 Aug 28.
Psoriasis is a chronic inflammatory disorder associated with increased cardiovascular mortality. Psoriasis affects high-density lipoprotein (HDL) composition, generating dysfunctional HDL particles. However, data regarding the impact of anti-psoriatic therapy on HDL composition and function are not available. HDL was isolated from 15 psoriatic patients at baseline and after effective topical and/or systemic anti-psoriatic therapy and from 15 age- and sex-matched healthy controls. HDL from psoriatic patients showed a significantly impaired capability to mobilize cholesterol from macrophages (6.4 vs. 8.0% [(3)H]cholesterol efflux, P<0.001), low paraoxonase (217 vs. 350 μM(-1) minute(-1) mg(-1) protein, P=0.011) and increased Lp-PLA2 activities (19.9 vs. 12.1 nM(-1) minute(-1) mg(-1) protein, P=0.028). Of particular interest, the anti-psoriatic therapy significantly improved serum lecithin-cholesterol acyltransferase activity and decreased total serum lipolytic activity but did not affect serum levels of HDL-cholesterol. Most importantly, these changes were associated with a significantly improved HDL-cholesterol efflux capability. Our results provide evidence that effective anti-psoriatic therapy recovers HDL composition and function, independent of serum HDL-cholesterol levels, and support to the emerging concept that HDL function may be a better marker of cardiovascular risk than HDL-cholesterol levels.
银屑病是一种与心血管死亡率增加相关的慢性炎症性疾病。银屑病影响高密度脂蛋白(HDL)的组成,产生功能失调的 HDL 颗粒。然而,关于抗银屑病治疗对 HDL 组成和功能的影响的数据尚不清楚。从 15 名银屑病患者的基线和有效的局部和/或全身抗银屑病治疗后以及 15 名年龄和性别匹配的健康对照者中分离出 HDL。银屑病患者的 HDL 显示出从巨噬细胞中动员胆固醇的能力明显受损(6.4%比 8.0%[3H]胆固醇流出,P<0.001),对氧磷酶活性降低(217 比 350 μM(-1)分钟(-1)mg(-1)蛋白,P=0.011)和脂蛋白相关的 PLA2 活性增加(19.9 比 12.1 nM(-1)分钟(-1)mg(-1)蛋白,P=0.028)。特别有趣的是,抗银屑病治疗显著改善了血清卵磷脂胆固醇酰基转移酶活性,降低了总血清脂解活性,但不影响血清 HDL-胆固醇水平。最重要的是,这些变化与 HDL-胆固醇流出能力的显著改善相关。我们的结果提供了证据,表明有效的抗银屑病治疗可以恢复 HDL 的组成和功能,而不依赖于血清 HDL-胆固醇水平,并支持这样一种新兴的概念,即 HDL 功能可能比 HDL-胆固醇水平更能作为心血管风险的标志物。