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

心肌损伤促进急性心肌梗死临床前模型中肾皮质基质金属蛋白酶-9 活性

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作者:Xiaoying Qiao #, Shreyas Bhave #, Lija Swain, Elric Zweck, Lara Reyelt, Paige Crowley, Shiva K Annamalai, Aditya Chennjorwala, Michele Esposito, Allen Razavi, Sina Foroutanjazi, Cody Machen, Katherine Thayer, Lena Jorde, Richard H Karas, Navin K Kapur

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.

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