期刊
ATHEROSCLEROSIS
卷 288, 期 -, 页码 175-185出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2019.05.005
关键词
Atherosclerosis; Computed tomography; Microarrays; Calcification; Carotid stenosis; Smooth muscle cells
资金
- European Union [722609]
- Swedish Heart and Lung Foundation
- Swedish Research Council [K2009-65X-2233-01-3, K201365X-06816-30-4, 349-2007-8703]
- Uppdrag Besegra Stroke [P581/2011-123]
- Stockholm County Council [ALF2011-0260, ALF-20110279]
- Swedish Society for Medical Research
- Tore Nilsson's Foundation
- Magnus Bergvall's Foundation
- Karolinska Institute Foundation
Background and aims: Unstable carotid atherosclerosis causes stroke, but methods to identify patients and lesions at risk are lacking. We recently found enrichment of genes associated with calcification in carotid plaques from asymptomatic patients. Here, we hypothesized that calcification represents a stabilising feature of plaques and investigated how macro-calcification, as estimated by computed tomography (CT), correlates with gene expression profiles in lesions. Methods: Plaque calcification was measured in pre-operative CT angiographies. Plaques were sorted into high- and low-calcified, profiled with microarrays, followed by bioinformatic analyses. Immunohistochemistry and qPCR were performed to evaluate the findings in plaques and arteries with medial calcification from chronic kidney disease patients. Results: Smooth muscle cell (SMC) markers were upregulated in high-calcified plaques and calcified plaques from symptomatic patients, whereas macrophage markers were downregulated. The most enriched processes in high-calcified plaques were related to SMCs and extracellular matrix (ECM) organization, while inflammation, lipid transport and chemokine signaling were repressed. These findings were confirmed in arteries with high medial calcification. Proteoglycan 4 (PRG4) was identified as the most upregulated gene in association with plaque calcification and found in the ECM, SMA+ and CD68+/TRAP + cells. Conclusions: Macro-calcification in carotid lesions correlated with a transcriptional profile typical for stable plaques, with altered SMC phenotype and ECM composition and repressed inflammation. PRG4, previously not described in atherosclerosis, was enriched in the calcified ECM and localized to activated macrophages and smooth muscle-like cells. This study strengthens the notion that assessment of calcification may aid evaluation of plaque phenotype and stroke risk.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据