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急性心肌梗死患者血清中骨形态发生蛋白 2 和 4 的水平。

Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction.

机构信息

Siberian State Medical University, 634055 Tomsk, Russia.

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, Russia.

出版信息

Cells. 2020 Sep 27;9(10):2179. doi: 10.3390/cells9102179.

Abstract

BACKGROUND

Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics.

METHODS

We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients ( = 31) during the six-month follow-up period after myocardial infarction (MI).

RESULTS

Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR.

CONCLUSIONS

Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.

摘要

背景

骨形态发生蛋白 2 和 4(BMPs)已被牵涉到左心室重构(LVR)过程中,如炎症和纤维化。我们假设这些知识可以转化为临床实践。

方法

我们研究了 31 例心肌梗死后 6 个月随访期间患者血清 BMP 水平的动态变化及其与 LVR 标志物和超声心动图参数的相关性。

结果

血清 BMPs 水平升高,6 个月随访时下降。BMP-2 从 MI 后第一天开始下降,BMP-4 从第 14 天开始下降。第 1 天 BMP-2 水平升高与肌钙蛋白 I 水平较低、再灌注时间较短和 6 个月随访时左心室射血分数(LV EF)较高有关。第 1 天 BMP-4 水平升高与可溶性肿瘤抑制因子 2(sST2)水平较低、年龄和再灌注时间较短有关。6 个月随访时 BMP-2 水平升高与 BMP-4、高敏 C 反应蛋白(hsCRP)和 sST2 水平升高有关。第 7 天 BMP-2 血清水平与 hsCRP 和基质金属蛋白酶(MMP)-9 水平升高有关。BMP-4 血清水平与第 3 天 hsCRP 和 MMP-9 水平较低、第 1 天 sST2 水平较低、第 7 天 LV EF 降低有关。多变量分析的结果支持 BMP-2 参与梗死后 LVR 的发展。

结论

我们的研究将关于 BMPs 在不良 LVR 发展中的实验数据转化为临床实践。MI 后 6 个月结束时,血清 BMPs 水平升高。BMP-2 从第一天开始下降,BMP-4 从第 14 天开始下降。BMP-2 和 BMP-4 与 LVR 的发展有关。它们与炎症标志物、细胞外基质降解、血流动力学应激和心肌损伤标志物的相关性进一步支持了我们的假设。进一步研究这些 BMPs 在体内梗死后 LVR 发展中的诊断和预测价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4d/7601292/8a3006755a91/cells-09-02179-g001.jpg

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