Etanercept or intravenous immunoglobulin attenuates expression of genes involved in post-myocardial infarction remodeling.
Etanercept or intravenous immunoglobulin attenuates expression of genes involved in post-myocardial infarction remodeling.
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DOI：
10.1016/j.cardiores.2005.02.016
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发表时间：
2005-07
影响因子：
10.8
通讯作者：
D. Gurantz;A. Yndestad;B. Halvorsen;O. Lunde;J. Omens;T. Ueland;P. Aukrust;C. Moore;J. Kjekshus;B. Greenberg
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文献类型：
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作者：
D. Gurantz;A. Yndestad;B. Halvorsen;O. Lunde;J. Omens;T. Ueland;P. Aukrust;C. Moore;J. Kjekshus;B. Greenberg
目的：急性心肌梗死（MI）后炎性细胞因子如肿瘤坏死因子（TNF）α水平持续升高可能导致适应不良的心室重构。本研究的目的是研究免疫调节治疗的影响与重组可溶性肿瘤坏死因子受体（TNFR：Fc）或静脉注射免疫球蛋白（IVIg）对左，右心室心肌梗死后remodelinginrats.Methods和结果：成年雄性Sprague-Dawley大鼠进行MI左冠状动脉结扎和随机治疗与车辆，TNFR：Fc，或IVIg和7天后处死。主要结论如下：（i）TNFR：与媒介物处理的对照相比，Fc和IVIg处理的大鼠发生较少的右心室（RV）肥大。(ii)MI后大鼠的LV和动脉压不受TNFR：Fc或IVIg治疗的影响。(iii)如通过实时RT-PCR所确定的，两种治疗都降低了肥大相关基因、心房利钠肽和β/α-肌球蛋白重链的比率以及与细胞外基质重塑相关的基因（即，胶原蛋白I和III、基质金属蛋白酶[MMP]-2及其组织抑制剂TIMP-1）。(iv)用IVIg治疗，而不是TNFR：Fc，降低RV中MMP-2酶谱活性以及TNFα和单核细胞趋化蛋白-1基因的表达。TNFR：Fc）和更一般的免疫调节方法（即，IVIg）在MI急性期减弱心脏重塑过程和相关基因的表达。这些发现提高了MI后开始免疫调节治疗可能有利于预防心力衰竭的后期发展的可能性。
Objective: Persistently elevated levels of inflammatory cytokines such as tumor necrosis factor (TNF)α after acute myocardial infarction (MI) may contribute to maladaptive ventricular remodeling. The aim of the present study was to examine the effects of immunomodulatory therapy with recombinant soluble TNF receptor (TNFR:Fc) or intravenous immunoglobulin (IVIg) on left and right ventricular post-MI remodeling in rats.Methods and results: Adult male Sprague–Dawley rats were subjected to MI by left coronary artery ligation and randomized to treatment with vehicle, TNFR:Fc, or IVIg and sacrificed after 7 days. The main findings were that: (i) TNFR:Fc- and IVIg-treated rats developed less right ventricular (RV) hypertrophy compared to vehicle-treated controls. (ii) LV and arterial pressures in post-MI rats were not affected by the TNFR:Fc or IVIg treatment. (iii) As determined by real-time RT-PCR, both treatments reduced the expression of the hypertrophy-related genes, atrial natriuretic peptide and the ratio of β/α-myosin heavy chains, and genes related to extracellular matrix remodeling (i.e., collagens I and III, matrix metalloproteinase [MMP]-2 and its tissue inhibitor TIMP-1) in the non-ischemic segment of LV and, in particular, in the RV. (iv) Treatment with IVIg, but not TNFR:Fc, reduced MMP-2 zymographic activity in the RV and the expression of genes for TNFα and monocyte chemoattractant protein-1.Conclusion: Therapy targeted directly against TNFα (i.e., TNFR:Fc) and a more general immunomodulatory approach (i.e., IVIg) in the acute phase of MI attenuates the cardiac remodeling process and expression of genes that are involved. These findings raise the possibility that initiation of immunomodulatory therapy post-MI could be beneficial in preventing the later development of heart failure.