Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC 3004, Australia.
Clin Sci (Lond). 2010 May 18;119(4):175-83. doi: 10.1042/CS20100011.
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.
在急性心肌梗死（MI）后左心室（LV）重构中，炎症和细胞外基质（ECM）重塑起着重要作用。先前的研究表明，急性 MI 患者的血浆 MMP（基质金属蛋白酶）水平升高，但它们的来源尚不清楚。单核细胞募集到梗死心肌对于炎症反应至关重要，但它们在 LV 重构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 MI 或稳定型心绞痛患者和健康对照者的血液样本中分离外周血单核细胞（PBMC）（分别为 14、8 和 12 例）。将 PBMC 培养 24 小时，通过明胶酶谱法测量培养基中 MMP9 的水平，并通过实时 PCR 测量 MMP9 基因表达。使用两个超阵列（ECM 和粘附分子，以及常见细胞因子；每个阵列包含 84 个基因）通过 5 例急性 MI 患者和 5 例对照者的 PBMC 筛选基因表达谱。我们发现，与两个对照组相比，急性 MI 患者的 PBMC 在 mRNA 和蛋白水平上的 MMP9 表达均增加了 2 倍（均 P<0.05）。值得注意的是，PBMC 不表达 MMP2。超阵列筛选显示，PBMC 不仅表达 MMPs、TIMPs（金属蛋白酶组织抑制剂）和基质蛋白，而且是细胞粘附分子、炎症细胞因子和生长因子的重要来源。与对照组相比，急性 MI 患者共有 42 个基因差异表达。通过实时 PCR 证实了所选基因的表达。总之，PBMC 是血浆 MMP9 升高的关键细胞来源，但不是 MMP2 的来源。PBMC 还参与急性 MI 中的全身和局部炎症及基质重塑。
