Jugdutt Bodh I, Palaniyappan Arivazhagan, Uwiera Richard R E, Idikio Halliday
Division of Cardiology, Department of Medicine, 2C2 Walter MacKenzie Health Sciences Centre, University of Alberta, Edmonton, AB, Canada.
Mol Cell Biochem. 2009 Feb;322(1-2):25-36. doi: 10.1007/s11010-008-9936-9. Epub 2008 Nov 5.
We assessed whether aging augments left ventricular (LV) damage, remodeling, and dysfunction and alters expression of healing-specific-matricellular proteins (HSMPs), matrix metalloproteinases (MMPs) and other pertinent proteins after acute reperfused-ST-segment-elevation myocardial infarction (RSTEMI) in the dog model. The findings suggest a novel role for HSMPs, MMPs, and the other proteins in the age-related increase in LV damage, remodeling, and dysfunction. Potentially detrimental effects of the altered proteins appear to outweigh beneficial effects and contribute to adverse outcome. Deleterious changes include the increase in matrix-degrading MMPs, inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, HSMPs such as secreted-protein-acidic-and-rich-in-cysteine (SPARC) and osteopontin (OPN), the blunted increase in endothelial-NOS (eNOS), and the decrease in IL-10 and neuronal NOS (nNOS). Potentially beneficial changes include increases in the HSMP secretory-leucocyte-protease-inhibitor (SLPI) and cytokine transforming growth factor (TGF)-beta(1). Targeting these proteins may mitigate enhanced LV remodeling and dysfunction with aging.
我们评估了在犬急性再灌注ST段抬高型心肌梗死（RSTEMI）模型中，衰老是否会加剧左心室（LV）损伤、重塑和功能障碍，并改变愈合特异性基质细胞蛋白（HSMPs）、基质金属蛋白酶（MMPs）及其他相关蛋白的表达。研究结果表明，HSMPs、MMPs和其他蛋白在与年龄相关的左心室损伤、重塑和功能障碍增加中具有新的作用。蛋白改变产生的潜在有害影响似乎超过有益影响，并导致不良后果。有害变化包括基质降解MMPs、诱导型一氧化氮合酶（iNOS）、促炎细胞因子白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α增加，分泌性富含半胱氨酸的酸性蛋白（SPARC）和骨桥蛋白（OPN）等HSMPs增加，内皮型一氧化氮合酶（eNOS）增加减弱，以及IL-10和神经元型一氧化氮合酶（nNOS）减少。潜在的有益变化包括HSMP分泌型白细胞蛋白酶抑制剂（SLPI）和细胞因子转化生长因子（TGF）-β1增加。针对这些蛋白可能会减轻衰老引起的左心室重塑和功能障碍增强。
