血液单核细胞衍生的巨噬细胞中的 C 反应蛋白水平与颈动脉粥样硬化病变中的含量呈显著相关性。
A significant correlation between C - reactive protein levels in blood monocytes derived macrophages versus content in carotid atherosclerotic lesions.
机构信息
Laboratory of Clinical Biochemistry, Rambam Health Care Campus, Haifa, Israel.
出版信息
J Inflamm (Lond). 2014 Mar 3;11(1):7. doi: 10.1186/1476-9255-11-7.
BACKGROUND
Atherosclerosis is a complex disease involving different cell types, including macrophages that play a major role in the inflammatory events occurring in atherogenesis. C-Reactive Protein (CRP) is a sensitive systemic marker of inflammation and was identified as a biomarker of cardiovascular diseases. Histological studies demonstrate CRP presence in human atherosclerotic lesions, and we have previously shown that macrophages express CRP mRNA. CRP could be locally secreted in the atherosclerotic lesion by arterial macrophages and local regulation of CRP could affect its pro-atherogenic effects. Moreover, human blood derived macrophages (HMDM) expression of CRP could reflect atherosclerotic lesion secretion of CRP.
METHODS
Ten type 2 diabetic patients and ten non-diabetic patients scheduled to undergo carotid endarterectomy were enrolled in this study, and their blood samples were used for serum CRP, lipid determination, and for preparation of HMDM further analyzed for their CRP mRNA expression and CRP content. Carotid lesions obtained from the patients were analyzed for their CRP and interleukin 6 (IL-6) content by immunohistochemistry.
RESULTS
Lesions from diabetic patients showed substantially higher CRP levels by 62% (p = 0.05) than lesions from non diabetic patients, and CRP staining that co-localized with arterial macrophages. CRP carotid lesion levels positively correlated with CRP mRNA expression (r2 = 0.661) and with CRP content (r2 = 0.611) in the patient's HMDM.
CONCLUSIONS
Diabetes up-regulated carotid plaques CRP levels and CRP measurements in HMDM could reflect atherosclerotic lesion macrophages secretion of CRP. Understanding the regulation of locally produced macrophage CRP in the arterial wall during atherogenesis could be of major importance in identifying the underlying mechanisms of inflammatory response pathways during atherogenesis.
背景
动脉粥样硬化是一种涉及多种细胞类型的复杂疾病，其中巨噬细胞在动脉粥样硬化发生的炎症事件中起主要作用。C 反应蛋白（CRP）是炎症的敏感系统标志物，被确定为心血管疾病的生物标志物。组织学研究表明 CRP 存在于人类动脉粥样硬化病变中，我们之前已经表明巨噬细胞表达 CRP mRNA。CRP 可由动脉巨噬细胞在动脉粥样硬化病变中局部分泌，CRP 的局部调节可能影响其促动脉粥样硬化作用。此外，人血来源的巨噬细胞（HMDM）CRP 的表达可反映动脉粥样硬化病变中 CRP 的分泌。
方法
本研究纳入了 10 名 2 型糖尿病患者和 10 名非糖尿病患者，他们接受颈动脉内膜切除术，采集其血样用于血清 CRP、血脂测定，并制备 HMDM，进一步分析其 CRP mRNA 表达和 CRP 含量。通过免疫组织化学分析患者颈动脉病变的 CRP 和白细胞介素 6（IL-6）含量。
结果
糖尿病患者的病变中 CRP 水平显著升高 62%（p=0.05），病变中 CRP 与动脉巨噬细胞共定位。CRP 颈动脉病变水平与患者 HMDM 中的 CRP mRNA 表达（r2=0.661）和 CRP 含量（r2=0.611）呈正相关。
结论
糖尿病上调了颈动脉斑块 CRP 水平，HMDM 中的 CRP 测量值可反映动脉粥样硬化病变中巨噬细胞 CRP 的分泌。了解动脉粥样硬化发生过程中动脉壁中局部产生的巨噬细胞 CRP 的调节作用，对于确定动脉粥样硬化发生过程中炎症反应途径的潜在机制可能具有重要意义。
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