Matrix metalloproteinases as drug targets in ischemia/reperfusion injury.

Drug Discov Today

Department for Molecular Biomedical Research, VIB, Ghent, Belgium.

Published: September 2011

Deficient blood supply (ischemia) is a common consequence of some surgical procedures and certain pathologies. Once blood circulation is re-established (reperfusion), a complex series of events results in recruitment of inflammatory cells, rearrangement of the extracellular matrix and induction of cell death, which lead to organ dysfunction. Although ischemia/reperfusion (I/R) injury is an important cause of death, there is no effective therapy targeting the molecular mechanism of disease progression. Matrix metalloproteinases (MMPs), which are important regulators of many cellular activities, have a central role in disease progression after I/R injury, as suggested by numerous studies using MMP inhibitors or MMP-deficient mice. Here, we review the involvement of MMP activity in the various processes following I/R injury and the therapeutic potential of MMP inhibition.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.drudis.2011.06.009DOI Listing

Publication Analysis

Top Keywords

i/r injury
12
matrix metalloproteinases
8
disease progression
8
metalloproteinases drug
4
drug targets
4
targets ischemia/reperfusion
4
injury
4
ischemia/reperfusion injury
4
injury deficient
4
deficient blood
4

Similar Publications

Neutrophil Elastase as A Potential Target in Ischemia-Reperfusion Injury.

Curr Vasc Pharmacol

January 2025

Department of Pharmacy, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Neutrophil elastase (NE), a major protease in neutrophils, is important in promoting inflammation and multiple pathological processes. While NE is released abundantly in ischemiareperfusion (I/R) injury, the intricate relationship between NE and I/R injury remains unclear. We examine several aspects of how NE is involved in I/R injury.

View Article and Find Full Text PDF

Hepatic ischemia-reperfusion injury (IRI) poses a significant threat to clinical outcomes and graft survival during hemorrhagic shock, hepatic resection, and liver transplantation. Current pharmacological interventions for hepatic IRI are inadequate. In this study, we identified ginsenoside Rk2 (Rk2), a rare dehydroprotopanaxadiol saponin, as a promising agent against hepatic IRI through high-throughput screening.

View Article and Find Full Text PDF

Introduction: The mechanism of remimazolam, a benzodiazepine that activates γ-aminobutyric acid a (GABAa) receptors, in cerebral ischemia/reperfusion (I/R) injury is not well understood. Therefore, we explored whether remimazolam activates protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β)/nuclear factor erythroid 2-related factor 2 (NRF2) to attenuate brain I/R injury in transcerebral I/R-injured rats and transoxygenic glucose deprivation/reperfusion (OGD/R)-injured SY5Y cells.

Material And Methods: Remimazolam was added at the beginning of cell and rat reperfusion, and the PI3K/AKT inhibitor LY294002 was added to inhibit the AKT/GSK-3β/NRF2 pathway 24 h before cellular OGD/R treatment and 30 min before rat brain I/R treatment.

View Article and Find Full Text PDF

5-(3-(-(Carboxymethyl)naphthalene-2-sulfonamido)phenyl)-1-ethyl-1-pyrrole-2-carboxylic acid as a Keap1-Nrf2 inhibitor for cerebral ischemia/reperfusion injury treatment.

RSC Adv

January 2025

Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area (Ningxia Medical University), Ministry of Education, School of Pharmacy, Ningxia Medical University 1160 Shengli Street Yinchuan 750004 China

The Keap1 (Kelch-like ECH-Associating Protein 1)-Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2)-ARE (Antioxidant Response Element) signaling pathway plays a crucial role in the oxidative stress response and has been linked to the development and progression of various diseases. Its influence on cerebral ischemia/reperfusion (I/R) injury has garnered significant attention. In our study, we investigated the effect of compound 2, a non-covalent inhibitor of the Keap1-Nrf2 interaction, which was previously discovered by our research group.

View Article and Find Full Text PDF

Background: Hepatic ischemia/reperfusion (I/R) injury (HIRI) is an intrinsic phenomenon observed in the process of various liver surgeries. Unfortunately, there are currently few options available to prevent HIRI. Accordingly, we aim to explore the role and key downstream effects of B-cell lymphoma 6 (BCL6) in hepatic I/R (HIR).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!