Soluble ST2 (interleukin 1 receptor-like 1) (sST2) is involved in inflammatory diseases and increased in heart failure (HF). We herein investigated sST2 effects on oxidative stress and inflammation in human cardiac fibroblasts and its pathological role in human aortic stenosis (AS). Using proteomics and immunodetection approaches, we have identified that sST2 down-regulated mitofusin-1 (MFN-1), a protein involved in mitochondrial fusion, in human cardiac fibroblasts. In parallel, sST2 increased nitrotyrosine, protein oxidation and peroxide production. Moreover, sST2 enhanced the secretion of pro-inflammatory cytokines interleukin (IL)-6, IL-1β and monocyte chemoattractant protein-1 (CCL-2). Pharmacological inhibition of transcriptional factor nuclear factor κB (NFκB) restored MFN-1 levels and improved oxidative status and inflammation in cardiac fibroblasts. Mito-Tempo, a mitochondria-specific superoxide scavenger, as well as Resveratrol, a general antioxidant, attenuated oxidative stress and inflammation induced by sST2. In myocardial biopsies from 26 AS patients, sST2 up-regulation paralleled a decrease in MFN-1. Cardiac sST2 inversely correlated with MFN-1 levels and positively associated with IL-6 and CCL-2 in myocardial biopsies from AS patients. sST2 affected mitochondrial fusion in human cardiac fibroblasts, increasing oxidative stress production and inflammatory markers secretion. The blockade of NFκB or mitochondrial reactive oxygen species restored MFN-1 expression, improving oxidative stress status and reducing inflammatory markers secretion. In human AS, cardiac sST2 levels associated with oxidative stress and inflammation. The present study reveals a new pathogenic pathway by which sST2 promotes oxidative stress and inflammation contributing to cardiac damage.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1042/CS20190475 | DOI Listing |
J Evid Based Integr Med
January 2025
Department of Biological Sciences, Faculty of Science, Beirut Arab University, Beirut, Lebanon.
Background: Polycystic Ovarian Syndrome (PCOS) is an endocrine disorder associated with increased risk of kidney and liver damage. Current treatments have shown contradictory outcomes, and their long-term use causes unwanted side effects. could serve as a complementary medicine to current PCOS treatments.
View Article and Find Full Text PDFZool Res
January 2025
Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, Guangdong 518057, China.
DNA2, a multifunctional enzyme with structure-specific nuclease, 5 -to-3 helicase, and DNA-dependent ATPase activities, plays a pivotal role in the cellular response to DNA damage. However, its involvement in cerebral ischemia/reperfusion (I/R) injury remains to be elucidated. This study investigated the involvement of DNA2 in cerebral I/R injury using conditional knockout (cKO) mice ( -Cre) subjected to middle cerebral artery occlusion (MCAO), an established model of cerebral I/R.
View Article and Find Full Text PDFACS Nano
January 2025
College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China.
Atopic dermatitis (AD) is a recurrent and chronic inflammatory skin condition characterized by a high lifetime prevalence and significant impairment of patients' quality of life, primarily due to intense itching and discomfort. However, current pharmacological interventions provide only moderate efficacy and are frequently accompanied by adverse side effects. The immune-pathogenesis of AD involves dysregulation of the Th2 immune response and exacerbation of inflammation related to excessive reactive oxygen species (ROS).
View Article and Find Full Text PDFFront Vet Sci
January 2025
Centre of Experimental and Clinical Regenerative Medicine, Small Animal Clinic, University of Veterinary Medicine and Pharmacy in Košice, Košice, Slovakia.
Eggshell membrane (ESM) is a rich source of bioactive compounds, including proteins, peptides, and antioxidants, contributing to its potential therapeutic benefits. These natural antioxidants might help neutralize reactive oxygen species (ROS) and modulate inflammatory responses, which are often linked with chondrocyte damage in osteoarthritis. In this study, we investigated the functional effects of ESM proteins on HO-induced oxidative stress in a neonatal canine chondrocytes.
View Article and Find Full Text PDFBackground: Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber by intestinal commensal bacteria, have demonstrated protective effects against acute lung injury (ALI) in animal models. However, the findings have shown variability across different studies. It is necessary to conduct a comprehensive evaluation of the efficacy of these treatments and their consistency.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!