Feature Inspection Section, Urumqi, Xin-Jiang Medical University, China.
Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3925-3935. doi: 10.26355/eurrev_201806_15278.
Inflammation and extracellular matrix degradation play a role in cardiac rupture (CR) after myocardial infarction (MI). It has been found that the expression of inflammatory cytokine S100A8/A9 was elevated in acute MI patients, whereas its impact in CR after infarction remains unclear.
Samples from cardiac tissue and peripheral blood of patients with CR after MI, MI, patients without CR, and healthy control (cardiotrauma) were collected to test the expressions of S100A8/A9, p-p65, and MMP-9. Co-culture system for HCF cells and macrophages were established to identify the impact of hypoxia-ischemia on the expressions of S100A8/A9 and TNFα. S100A9 and/or TNFα blocking agent were applied to examine the effect on macrophages migration, expressions of S100A8, S100A9, and TNFα. Western blot was adopted to determine levels of p-p65 and MMP-9 protein after the inhibition of S100A9 and/or TNFα.
Compared with healthy control and non-CR patients, serum S100A8/A9 and MMP-9 levels were elevated in cardiac tissues of CR patients, while S100A8/A9, p-p65, and MMP-9 were also overexpressed. Hypoxia-ischemia significantly caused the increasing levels of S100A8/A9 and TNFα in macrophages (p < 0.05). The blockade of S100A9 and/or TNFα suppressed the activation and migration of macrophages. The inhibition of S100A9 expression also decreased the secretion of TNFα in macrophages, while the suppression of TNFα showed no significant impact on S100A8 and S100A9 levels. Downregulation of TNFα or NF-κB markedly declined p-p65 and MMP-9 protein levels in HCF cells from co-culture system or single culture, whereas the blockade of S100A9 only reduced their expressions in co-cultured HCF cells.
The level of S100A8/A9 was upregulated in MI patients with CR. S100A8/A9 induced the activation of NF-κB and expression of MMP-9 protein in HCF cells through facilitating secretion of TNFα from macrophages, which may play a role in triggering extracellular matrix degradation and CR.
炎症和细胞外基质降解在心肌梗死后心脏破裂（CR）中起作用。已经发现，在急性 MI 患者中，炎症细胞因子 S100A8/A9 的表达升高，但其在梗死后 CR 中的影响尚不清楚。
收集 MI 后 CR 患者、MI 患者、无 CR 患者和健康对照（心肌创伤）的心脏组织和外周血样本，以检测 S100A8/A9、p-p65 和 MMP-9 的表达。建立 HCF 细胞和巨噬细胞的共培养系统，以确定缺氧缺血对 S100A8/A9 和 TNFα 表达的影响。应用 S100A9 和/或 TNFα 阻断剂，观察对巨噬细胞迁移、S100A8、S100A9 和 TNFα 表达的影响。采用 Western blot 法检测 S100A9 和/或 TNFα 抑制后 p-p65 和 MMP-9 蛋白水平。
与健康对照组和非 CR 患者相比，CR 患者心脏组织中血清 S100A8/A9 和 MMP-9 水平升高，同时 S100A8/A9、p-p65 和 MMP-9 也过度表达。缺氧缺血明显导致巨噬细胞中 S100A8/A9 和 TNFα 水平升高（p<0.05）。S100A9 和/或 TNFα 阻断抑制了巨噬细胞的激活和迁移。S100A9 表达抑制也降低了巨噬细胞中 TNFα 的分泌，而 TNFα 的抑制对 S100A8 和 S100A9 水平没有显著影响。下调 TNFα 或 NF-κB 显著降低共培养或单培养的 HCF 细胞中 p-p65 和 MMP-9 蛋白水平，而 S100A9 阻断仅降低共培养的 HCF 细胞中的表达。
CR 后 MI 患者 S100A8/A9 水平升高。S100A8/A9 通过促进巨噬细胞中 TNFα 的分泌，诱导 HCF 细胞中 NF-κB 的激活和 MMP-9 蛋白的表达，这可能在触发细胞外基质降解和 CR 中起作用。
