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心肌损伤促进急性心肌梗死临床前模型肾皮质中基质金属蛋白酶-9 的活性。

Myocardial Injury Promotes Matrix Metalloproteinase-9 Activity in the Renal Cortex in Preclinical Models of Acute Myocardial Infarction.

机构信息

Molecular Cardiology Research Institute, Surgical and Interventional Research Laboratories, and The CardioVascular Center, Tufts Medical Center, 800 Washington Street Box # 80, Boston, MA, 02111, USA.

出版信息

J Cardiovasc Transl Res. 2022 Apr;15(2):207-216. doi: 10.1007/s12265-021-10114-y. Epub 2021 Mar 29.

Abstract

New mechanistic insight into how the kidney responds to cardiac injury during acute myocardial infarction (AMI) is required. We hypothesized that AMI promotes inflammation and matrix metalloproteinase-9 (MMP9) activity in the kidney and studied the effect of initiating an Impella CP or veno-arterial extracorporeal membrane oxygenation (VA-ECMO) before coronary reperfusion during AMI. Adult male swine were subjected to coronary occlusion and either reperfusion (ischemia-reperfusion; IR) or support with either Impella or VA-ECMO before reperfusion. IR and ECMO increased while Impella reduced levels of MMP-9 in the myocardial infarct zone, circulation, and renal cortex. Compared to IR, Impella reduced myocardial infarct size and urinary KIM-1 levels, but VA-ECMO did not. IR and VA-ECMO increased pro-fibrogenic signaling via transforming growth factor-beta and endoglin in the renal cortex, but Impella did not. These findings identify that AMI increases inflammatory activity in the kidney, which may be attenuated by Impella support.

摘要

需要深入了解肾脏在急性心肌梗死(AMI)期间对心脏损伤的反应机制。我们假设 AMI 会促进肾脏的炎症和基质金属蛋白酶-9(MMP9)活性,并研究在 AMI 期间冠状动脉再灌注前开始使用 Impella CP 或静脉-动脉体外膜肺氧合(VA-ECMO)对其的影响。成年雄性猪经历冠状动脉闭塞,再灌注(缺血再灌注;IR)或在再灌注前使用 Impella 或 VA-ECMO 进行支持。IR 和 ECMO 增加,而 Impella 在心肌梗死区、循环和肾皮质中降低 MMP-9 水平。与 IR 相比,Impella 降低了心肌梗死面积和尿 KIM-1 水平,但 VA-ECMO 没有。IR 和 VA-ECMO 通过转化生长因子-β和内皮素在肾皮质中增加了促纤维化信号,但 Impella 没有。这些发现表明 AMI 增加了肾脏的炎症活性,Impella 支持可能会减轻这种活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5b/8983528/3f87471bfcab/12265_2021_10114_Fig1_HTML.jpg

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