Department of Vascular Surgery, Semmelweis University, Városmajor u. 68, Budapest, Hungary.
Cell Stress Chaperones. 2011 May;16(3):257-65. doi: 10.1007/s12192-010-0237-3. Epub 2010 Nov 3.
It has been previously reported that serum levels of 70-kDa heat shock protein (Hsp70) are elevated in peripheral artery disease. The aim of the present study was to examine whether increased serum Hsp70 levels are related to the extent of arterial calcification and standard laboratory parameters of patients with peripheral artery disease, as well as to markers of inflammation (C-reactive protein), atherosclerosis (homocysteine), and calcification (fetuin-a). One hundred eighty chronic atherosclerotic patients with significant carotid stenosis and/or lower extremity vascular disease were enrolled in this cross-sectional study. Systemic atherosclerosis and calcification was assessed by ultrasound (carotid intima-media thickness (IMT), presence of calcification at the abdominal aorta, carotid and femoral bifurcations, and aortic and mitral cardiac valves). Standard serum markers of inflammation, diabetes, renal function, ankle-brachial indexes, and traditional risk factors for atherosclerosis were noted. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay. Standard laboratory parameters (clinical chemistry), C-reactive protein (CRP), and homocysteine levels were determined by an autoanalyzer using the manufacturer's kits. Fetuin-a levels were measured by radial immunodiffusion. Patients' median age was 64 (57-71) years, 69% were men, and 34.5% had diabetes. Serum heat shock protein 70 levels were significantly higher in patients with more severe arterial calcification (p < 0.02) and showed significant positive correlations with serum bilirubin (r = 0.23, p = 0.002) and homocysteine levels (r = 0.18, p = 0.02). Serum Hsp70 did not correlate with body mass index, IMT, CRP, or fetuin-a levels in this cohort. Logistic regression analysis confirmed the association between sHsp70 and calcification score (OR, 2.189; CI, 1.156-4.144, p = 0.016) and this correlation remained significant (OR, 2.264; CI, 1.021-5.020, p = 0.044) after the adjustment for age, sex, eGFR, smoking, CRP, and homocysteine levels. Our data show that serum Hsp70 levels correlate with the severity of atherosclerosis in patients with carotid artery disease and chronic lower limb ischemia. These data support a putative role for plasma Hsp70 in the development of arterial calcification. Nevertheless, further studies are required to investigate the usefulness of circulating Hsp70 level as a marker of atherosclerotic calcification.
先前已有报道称，70kDa 热休克蛋白（Hsp70）的血清水平在周围动脉疾病中升高。本研究旨在探讨血清 Hsp70 水平升高是否与周围动脉疾病患者的动脉钙化程度和标准实验室参数相关，以及与炎症标志物（C 反应蛋白）、动脉粥样硬化标志物（同型半胱氨酸）和钙化标志物（胎球蛋白 A）相关。本横断面研究纳入了 180 例患有明显颈动脉狭窄和/或下肢血管疾病的慢性动脉粥样硬化患者。通过超声（颈动脉内膜中层厚度（IMT）、腹主动脉、颈动脉和股动脉分叉处、主动脉和二尖瓣心脏瓣膜处的钙化存在情况）评估系统性动脉粥样硬化和钙化。记录了炎症、糖尿病、肾功能、踝臂指数的标准血清标志物以及传统的动脉粥样硬化危险因素。采用酶联免疫吸附试验测定血清 Hsp70 水平。采用自动分析仪和制造商试剂盒测定常规实验室参数（临床化学）、C 反应蛋白（CRP）和同型半胱氨酸水平。采用放射免疫扩散法测定胎球蛋白 A 水平。患者的中位年龄为 64（57-71）岁，69%为男性，34.5%患有糖尿病。血清热休克蛋白 70 水平在动脉钙化程度更严重的患者中明显升高（p<0.02），并且与血清胆红素水平呈显著正相关（r=0.23，p=0.002）和同型半胱氨酸水平（r=0.18，p=0.02）。在该队列中，血清 Hsp70 与体重指数、IMT、CRP 或胎球蛋白 A 水平无相关性。Logistic 回归分析证实 sHsp70 与钙化评分之间存在关联（OR，2.189；95%CI，1.156-4.144，p=0.016），且在调整年龄、性别、eGFR、吸烟、CRP 和同型半胱氨酸水平后该相关性仍然显著（OR，2.264；95%CI，1.021-5.020，p=0.044）。我们的数据表明，血清 Hsp70 水平与颈动脉疾病和慢性下肢缺血患者的动脉粥样硬化严重程度相关。这些数据支持血浆 Hsp70 在动脉钙化发展中的潜在作用。然而，需要进一步的研究来探讨循环 Hsp70 水平作为动脉粥样硬化钙化标志物的有用性。
