PPAR- Activation Prevents Septic Cardiac Dysfunction via Inhibition of Apoptosis and Necroptosis.

Oxid Med Cell Longev

Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

Published: April 2018

Sepsis-induced cardiac dysfunction remains one of the major causes of death in intensive care units. Overwhelmed inflammatory response and unrestrained cell death play critical roles in sepsis-induced cardiac dysfunction. Peroxisome proliferator-activated receptor- (PPAR-) has been proven to be cardioprotective in sepsis. However, the mechanism of PPAR--mediated cardioprotection and its relationship with inflammation and cell death are unclear. We hypothesized that activation of PPAR- by reducing cardiac inflammation, myocardial apoptosis, and necroptosis may prevent myocardial dysfunction in sepsis. Rats were subjected to cecal ligation and puncture (CLP) with or without PPAR- agonist (rosiglitazone) or antagonist T0070907 (T007). After CLP, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated proinflammatory cytokines, and increased apoptosis, necrosis, and necroptosis. This process is corresponded with decreased inhibitor B (IB) and increased NF-B, receptor-interacting protein kinase-1 (RIP1), RIP3, and mixed lineage kinase-like (MLKL) protein. Activation of PPAR- by rosiglitazone pretreatment enhanced PPAR- activity and prevented these changes, thereby improving the survival of septic rats. In contrast, inhibition of PPAR- by T007 further exacerbated the condition, dropping the survival rate to nearly 0%. In conclusion, PPAR- activation by reducing proinflammatory cytokines, apoptosis, and necroptosis in the myocardium prevents septic myocardial dysfunction.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560091PMC
http://dx.doi.org/10.1155/2017/8326749DOI Listing

Publication Analysis

Top Keywords

cardiac dysfunction
12
apoptosis necroptosis
12
ppar-
8
ppar- activation
8
prevents septic
8
sepsis-induced cardiac
8
cell death
8
activation ppar-
8
myocardial dysfunction
8
proinflammatory cytokines
8

Similar Publications

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!