Shamaei-Tousi Alireza, Stephens Jeffrey W, Bin Ren, Cooper Jacqueline A, Steptoe Andrew, Coates Anthony R M, Henderson Brian, Humphries Steve E
Division of Microbial Diseases, UCL Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK.
Eur Heart J. 2006 Jul;27(13):1565-70. doi: 10.1093/eurheartj/ehl081. Epub 2006 Jun 8.
Evidence is accumulating to support the hypothesis that the release of heat shock protein (Hsp)60 into the circulation is associated with the development of coronary heart disease (CHD). As diabetes is a risk factor for CHD, it was of interest to determine Hsp60 blood levels in a cross-sectional cohort of diabetic patients, some of whom had cardiovascular disease, and relate levels to relevant biochemical markers.
A total of 855 patients with T1DM or T2DM, recruited as part of the UCL Diabetes and Cardiovascular disease Study (UDACS), were assayed for plasma levels of Hsp60. Immunoreactive Hsp60 was detected in 54% of the samples, with 26% having plasma levels > 1 microg/mL. Levels of Hsp60 were higher in Caucasians than in other ethnic groupings, with 56.5% of Caucasian subjects, 37.5% of African-Caribbean subjects, and 47.1% of Indian subjects having detectable levels (P = 0.007), and with a higher proportion of non-smokers having detectable Hsp60 levels than smokers (54.9 vs. 43.5%, P = 0.01). Of note was the finding of an association between higher mean plasma levels of Hsp60 in subjects with clinically manifest cardiovascular disease and those with a history of myocardial infarction having an adjusted odds ratio of having detectable Hsp60 of 2.17 (CI 1.26-3.73).
This is the first report of circulating Hsp60 levels in diabetic patients, which suggests that this secreted mitochondrial cell stress protein may be playing an unexpected role in the cardiovascular pathology associated with diabetes.
越来越多的证据支持如下假说,即热休克蛋白(Hsp)60释放到循环系统中与冠心病(CHD)的发生有关。由于糖尿病是冠心病的一个危险因素,因此测定一组糖尿病患者(其中一些患有心血管疾病)横断面队列中的Hsp60血液水平,并将这些水平与相关生化标志物联系起来,是很有意义的。
作为伦敦大学学院糖尿病与心血管疾病研究(UDACS)的一部分,共招募了855例1型糖尿病或2型糖尿病患者,检测其血浆Hsp60水平。54%的样本中检测到免疫反应性Hsp60,其中26%的血浆水平>1μg/mL。白种人中Hsp60水平高于其他种族,56.5%的白种人、37.5%的非裔加勒比人和47.1%的印度人检测到可检测水平(P = 0.007),且不吸烟者中Hsp60可检测水平的比例高于吸烟者(54.9%对43.5%,P = 0.01)。值得注意的是,在有临床表现的心血管疾病患者和有心肌梗死病史的患者中,较高的平均血浆Hsp60水平与可检测到Hsp60的调整优势比为2.17(CI 1.26 - 3.73)之间存在关联。
这是关于糖尿病患者循环Hsp60水平的首次报告,表明这种分泌的线粒体细胞应激蛋白可能在与糖尿病相关的心血管病理过程中发挥意想不到的作用。