高脂血症患者粘附分子水平及调脂干预的研究

目的　观察高脂血症患者可溶性 P-选择素 ( s P- sel)和可溶性细胞间粘附分子 - 1( s ICAM- 1)的表达及阿托伐他汀的调脂干预的作用。方法　用酶联免疫吸附法 ( EL ISA)及放免法检测 32例高脂血症患者 (男 19例 ,女 13例 )服用阿托伐他汀 ( 10 mg/ d,疗程 4～ 6周 )前后血浆 s ICAM- 1和 s P- sel的水平并与性别、年龄相匹配的 30例正常血脂组对照。结果　高脂血症患者血浆 s ICAM- 1和 s P- sel的水平明显高于对照组 ( P<0 .0 1) ;阿托伐他汀治疗 4～ 6周后总胆固醇 ( TC)、甘油三酯 ( TG)、低密度脂蛋白胆固醇 ( L DL - C)、s ICAM- 1和 s P- sel的水平显著下降 ( P<0 .0 1) ;s ICAM- 1和 s P- sel与 TC、L DL- C、TG呈正相关 ( P<0 .0 5 ) ,HDL- C升高不明显。结论　 1)血浆 s ICAM- 1和s P- sel的表达增加推测是高脂血症致动脉粥样硬化的一个重要环节 ;2 )阿托伐他汀降低 s ICAM- 1和 s P- sel水平可能主要是通过调节血脂而产生。     

过敏性紫癜患儿血清sE一选择素和sP一选择素水平的变化及其意义

目的：研究过敏性紫癜（HSP）患儿血清sE选择素和sP一选择素水平变化,探讨其在HSP发病机制中的作用。方法：以30例健康儿童为对照组,将80例初发HSP患儿按尿常规结果分为HSP组（49例）和HSPN组（3l例）,两组分别于急性期和恢复期采血测定sE一选择素和sP一选择素,同时测定血清中胱抑素C（CysC）的浓度,并将胱抑素C（CysC）水平与外周血sE一选择素和sP一选择素进行相关分析。结果：HSP和HSPN患儿血清sE一选择素和sP一选择素水平高于对照组,差异有统计学意义（P〈0．05）;HSPN组sE－选择素和sP一选择素水平明显高于HSP组,且差异有统计学意义（P〈0．05）;患儿外周血sE一选择素和sP－选择素水平与胱抑素C（CysC）水平呈正的直线关系（r＝0．589,P〈0．01）。结论：sE一选择素和sP选择素可能参与HSP急性期血管内皮细胞炎性以及脏器损伤的机制,对过敏性紫癜早期诊断具有良好的临床价值。     

Soluble CD40 ligand and soluble P-selectin levels in Gilbert's syndrome: A link to protection against atherosclerosis?

Objective

To investigate the role of CD40 ligand and P-selectin in the mechanism of decreased incidence of cardiovascular disease in Gilbert's syndrome (GS).

Design and methods

The soluble forms of CD40 ligand (sCD40L) and P-selectin (sP-selectin), and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS (n = 25) and compared to healthy controls (n = 53).

Results

sCD40L and hs-CRP levels were significantly lower in GS compared to the controls (0.33 ± 0.27 vs 0.71 ± 0.37 ng/mL, p < 0.001 and 0.51 ± 0.45 vs 1.16 ± 1.31 mg/L, p = 0.046, respectively). Both sCD40L and hs-CRP were negatively correlated with total bilirubin (r = − 0.5, p < 0.001 and r = − 0.34, p = 0.002, respectively). sP-selectin levels were lower in GS when compared to the controls but the difference did not reach statistical significance (p = 0.052). No correlation was found between the plasma levels of sCD40L, sP-selectin and hs-CRP.

Conclusion

These novel findings suggest that reduced sCD40L and hs-CRP concentrations may have a role in the mechanism of protection against atherosclerosis in GS.     

Umbilical sP-selectin levels are different in preeclamptic pregnancies with intrauterine normal growth and growth restricted fetus

Objective.?The aim of this study was the analysis of the umbilical cord serum sP-selectin levels in pregnancies complicated by severe preeclampsia with and without intrauterine growth restriction and in normotensive pregnancies.

Patients and methods. The study was carried out on 18 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group P) and 18 pregnant patients with severe preeclampsia complicated by intrauterine fetal growth restriction (IUGR) (group PI). The control group consisted of 34 patients with singleton uncomplicated pregnancies (group C). Umbilical serum sP-selectin concentrations were estimated using a sandwich ELISA assay according to the manufacturer's instruction (ELISA kit Bender MedSystems Vienna, Austria).

Results.?Our study revealed different concentrations of soluble P-selectin in the umbilical cord in our both studied groups of preeclamptic women with and without IUGR. The umbilical cord levels of sP-selectin were decreased in the group with preeclampsia complicated by IUGR and increased in the preeclamptic women with the normal intrauterine fetal growth. The mean values of umbilical sP-selectin were 839.008?±?625.703?ng/ml in group P, 275.873?±?174.339?ng/ml in group PI, and 288.719?±?199.039?ng/ml in the control group, respectively.

Conclusions.?Higher levels of the umbilical sP-selectin may confirm the presence of platelet and endothelial cell activation and confirm a hypercoagulant state in preeclamptic disorder, especially in preeclampsia without IUGR.     

High levels of platelet-monocyte aggregates after valve replacement for aortic stenosis: relation to soluble P-selectin and P-selectin glycoprotein ligand-1 genes

Background

Calcific aortic valve stenosis is linked to atherosclerosis. The latter is associated with increased levels of platelets adhering to monocytes (PMA).

Objective

The hemodynamic impairment in symptomatic aortic valve stenosis can be abated by valve replacement. We investigated the effect of valve replacement on PMA and receptor-ligand axis P-selectin - P-selectin glycoprotein ligand-1 (PSGL-1) in severe aortic valve stenosis.

Patients and Methods

PMA, plasma P-selectin (sP-selectin) and polymorphisms within the coding region for PSGL-1 (SELPLG) were determined in 42 patients with severe aortic valve stenosis before and 4 to 8 months after valve replacement. Ten patients suffered from significant coronary artery disease and received also a coronary artery bypass graft. Thirty-four patients received a bioprosthetic valve and 8 patients who were < 65 years old received a mechanical valve.

Results

Before the intervention, PMA levels were significantly higher in patients with aortic valve stenosis than in two control cohorts, namely healthy indviduals and 88 age- and sex-matched patients with severe atherosclerosis, but without aortic valve stenosis (p < 0.001). PMA decreased after surgery, but normalized in only 3 patients, while further increases were noted in 11 patients. sP-selectin was elevated in 3 and 4 patients before and after valve replacement, respectively. sP-selectin increased significantly after surgery, but remained within the normal range. There was no correlation between changes of PMA and sP-selectin or any of the polymorphisms within SELPLG.

Conclusions

Exceedingly high PMA in aortic stenosis are independent of SELPLG polymorphisms, and largely of the hemodynamic compromise caused by the stenotic valve.     

Influence of renal function and platelet turnover on the antiplatelet effect of aspirin

Introduction

Kidney disease predisposes to cardiovascular events. This study investigated the influence of renal function and platelet turnover on the antiplatelet effect of aspirin in patients with coronary artery disease.

Materials and Methods

We included 124 aspirin-treated patients with coronary artery disease and normal to moderately reduced renal function. All tests were performed one hour after aspirin ingestion. Renal function was assessed using creatinine, estimated glomerular filtration rate (eGFR), and cystatin C. The antiplatelet effect of aspirin was evaluated using the VerifyNow® Aspirin assay and multiple electrode aggregometry (MEA, Multiplate®) induced by collagen (1.0 μg/mL) and arachidonic acid (1.0 mmol/L). Von Willebrand factor was measured as a marker of endothelial dysfunction. Platelet turnover was evaluated by measurements of immature, reticulated platelets.

Results

Renal function did not influence the antiplatelet effect of aspirin evaluated by MEA (r = − 0.2-0.09, p = 0.03-0.77) or the VerifyNow® (r = − 0.12-0.11, all p-values > 0.1). In contrast, renal function correlated inversely with von Willebrand factor levels (r_creatinine = 0.48, p < 0.0001; r_eGFR = − 0.46, p < 0.001; r_{cystatin C} = 0.54, p < 0.0001). The number of immature platelets correlated with platelet aggregation according to MEA (r = 0.20-0.39, all p-values < 0.03), but not according to VerifyNow® (r = − 0.07, p = 0.50).

Conclusions

A reduced antiplatelet effect of aspirin may be explained by an increased number of immature platelets. Moderately impaired renal function was associated with high levels of von Willebrand factor, but not with a reduced antiplatelet effect of aspirin.