Activation of peripheral blood mononuclear cells and extracellular matrix and inflammatory gene profile in acute myocardial infarction
Activation of peripheral blood mononuclear cells and extracellular matrix and inflammatory gene profile in acute myocardial infarction
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DOI：
10.1042/cs20100011
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发表时间：
2010-08-01
期刊：
影响因子：
6
通讯作者：
Dart, Anthony M.
中科院分区：
文献类型：
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作者：
Fang, Lu;Du, Xiao-Jun;Dart, Anthony M.
炎症和细胞外基质（ECM）重塑在急性心肌梗死（MI）后左心室（LV）重塑中起重要作用。既往研究显示急性心肌梗死患者血浆基质金属蛋白酶（MMP）水平升高，但其来源尚不清楚。单个核细胞向梗死心肌的募集对于炎症反应至关重要，但它们在LV重塑中的确切作用尚未得到充分研究，因为难以分离和研究局部炎症细胞的功能。为了解决这些问题，我们从急性心肌梗死或稳定型心绞痛患者或健康对照者的血液样品中分离PBMC（外周血单核细胞）（分别为n=14、8和12）。PBMCs培养24 h，明胶酶谱法检测培养液中MMP 9水平，实时荧光定量PCR检测MMP 9基因表达。两个超阵列（ECM和粘附分子，和常见的细胞因子; 84个基因包括在每个阵列）被用来筛选PBMCs的基因表达谱在5例急性心肌梗死患者和5个对照。我们发现，MMP 9在mRNA和蛋白水平的表达在急性MI患者的PBMC中增加2倍（均P < 0.05）与两个对照组相比。值得注意的是，PBMC不表达MMP 2。超阵列筛选结果显示，PBMCs不仅表达MMPs、TIMPs（组织金属蛋白酶抑制剂）和基质蛋白，而且是细胞粘附分子、炎性细胞因子和生长因子的重要来源。与对照组相比，急性心肌梗死患者中共有42个基因差异表达。通过实时PCR证实所选基因的表达。总之，PBMC是血浆MMP 9升高的关键细胞来源，但不是MMP 2。PBMC还有助于急性MI中的全身和区域炎症以及基质重塑。
Inflammation and ECM (extracellular matrix) remodelling play important roles in LV (left ventricular) remodelling following acute MI (myocardial infarction). Previous studies show elevated plasma MMP (matrix metalloproteinase) levels in patients with acute MI, but their sources are not clear. The recruitment of mononuclear cells into the infarcted myocardium is critical for inflammatory responses, but their exact roles in LV remodelling have not been fully investigated, as it is difficult to isolate and study the function of regional inflammatory cells. To address these questions, we isolated PBMCs (peripheral blood mononuclear cells) from blood samples of patients with acute MI or stable angina, or healthy controls (n=14, 8 and 12 respectively). PBMCs were cultured for 24 h and the MMP9 level in the culture medium was measured by gelatin zymography, and MMP9 gene expression was measured by real-time PCR. Two superarrays (ECM and adhesion molecules, and common cytokines; 84 genes included in each array) were employed to screen gene expression profiles by PBMCs in five patients with acute MI and five controls. We found that MMP9 expression by PBMCs at both the mRNA and protein levels was increased 2-fold (both P < 0.05) in patients with acute MI compared with the two control groups. Notably, MMP2 was not expressed by PBMCs. Superarray screening revealed that PBMCs not only expressed MMPs, TIMPs (tissue inhibitors of metalloproteinases) and matrix proteins, but also served as an important source of cell adhesion molecules, inflammatory cytokines and growth factors. A total of 42 genes were differentially expressed in patients with acute MI compared with controls. Expression of selected genes was confirmed by real-time PCR. In conclusion, PBMCs constitute a key cellular source for elevated plasma MMP9, but not for MMP2. PBMCs also contribute to systemic and regional inflammation and matrix remodelling in acute MI.