The Role of Matrix Metalloproteinases in Hemorrhagic Transformation in the Treatment of Stroke with Tissue Plasminogen Activator

Author:

Babenko Valentina A.1,Fedulova Ksenia S.1,Silachev Denis N.1,Rahimi-Moghaddam Parvaneh2ORCID,Kalyuzhnaya Yulia N.3,Demyanenko Svetlana V.3,Plotnikov Egor Y.1ORCID

Affiliation:

1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

2. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran 14496-14535, Iran

3. Academy of Biology and Biotechnology, Southern Federal University, 344090 Rostov-on-Don, Russia

Abstract

Ischemic stroke is a leading cause of disability and mortality worldwide. The only approved treatment for ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA), though this approach often leads to a severe complication: hemorrhagic transformation (HT). The pathophysiology of HT in response to tPA is complex and not fully understood. However, numerous scientific findings suggest that the enzymatic activity and expression of matrix metalloproteinases (MMPs) in brain tissue play a crucial role. In this review article, we summarize the current knowledge of the functioning of various MMPs at different stages of ischemic stroke development and their association with HT. We also discuss the mechanisms that underlie the effect of tPA on MMPs as the main cause of the adverse effects of thrombolytic therapy. Finally, we describe recent research that aimed to develop new strategies to modulate MMP activity to improve the efficacy of thrombolytic therapy. The ultimate goal is to provide more targeted and personalized treatment options for patients with ischemic stroke to minimize complications and improve clinical outcomes.

Funder

Russian Foundation for Basic Research

Iran National Science Foundation (INSF) and the Russian Foundation

Russian Science Foundation

Publisher

MDPI AG

Subject

Medicine (miscellaneous)

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