کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5947917 1172375 2013 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Increased expression of heparanase in symptomatic carotid atherosclerosis
ترجمه فارسی عنوان
افزایش بیان هپارناز در آترواسکلروز عروق کرونری
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
چکیده انگلیسی

ObjectiveProliferation of smooth muscle cells (SMCs) can stabilize atherosclerotic lesions but the molecular mechanisms that regulate this process in humans are largely unknown. We have previously shown that heparan sulfate proteoglycans (HSPGs), such as perlecan, regulate SMC growth in animal models by modulating heparin-binding mitogens. Since perlecan is expressed at low levels in human atherosclerosis, we speculated that the effect of heparan sulfate (HS) in human disease was rather influenced by HS degradation and investigated the expression of heparanase (HPSE) in human carotid endarterectomies.Methods and resultsGene expression analysis from 127 endarterectomies in the BiKE database revealed increased expression of HPSE in carotid plaques compared with normal arteries, and a further elevation in symptomatic lesions. Increased HPSE protein expression in symptomatic plaque tissue was verified by tissue microarrays. HPSE mRNA levels correlated positively with expression of inflammatory markers IL-18, RANTES and IL-1β, and also T-cell co-stimulatory molecules, such as B7.2, CD28, LFA-1 and 4-1BB. Previously reported single nucleotide polymorphisms within HPSE were associated with differential mRNA expression in plaques. Immunohistochemistry revealed that inflammatory cells were major producers of HPSE in plaque tissue. HPSE immunoreactivity was also observed in SMCs adjacent to the necrotic core and was co-localized to deposits of fibrin.ConclusionsThis study demonstrates increased expression of HPSE in human atherosclerosis associated with inflammation, coagulation and plaque instability. Since HS can regulate SMC proliferation and influence plaque stability, the findings suggest that HPSE degradation of HS take part in the regulation of SMC function in human atherosclerosis.

► HPSE expression increased in carotid plaques and further elevated in symptomatic lesions. ► Polymorphisms in the HPSE gene strongly influenced HPSE expression in carotid plaques. ► Strong correlations between HPSE expression and markers of plaque instability. ► HPSE co-localized with deposited fibrin, in presence and absence of platelets. ► HPSE possibly contributes to plaque instability by a number of different mechanisms.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 226, Issue 1, January 2013, Pages 67-73
نویسندگان
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