SEW2871 attenuates myocyte necroptosis in heart failure through inhibition of oxidative stress and inflammatory cytokines

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Background and Purpose Sphingosine‐1‐phosphate (S1P)/S1P receptor signalling exerts cardioprotective effects. However, the effect of selective S1P 1 agonist SEW2871 on myocyte necroptosis in heart failure underlying mechanisms are unknown. In present study, we tested hypothesis that attenuates through inhibition oxidative stress inflammatory cytokines. Experimental Approach Eight‐week‐old male C57BL/6J mice underwent myocardial infarction (MI) or sham operation. The animals were randomized to receive (5 mg·kg −1 ·day , i.p) placebo for 4 weeks. Key Results MI exhibited increases left ventricular (LV) end‐diastolic dimension, LV end‐systolic mass lung weight a decrease ejection fraction, indicating dilation, systolic dysfunction congestion, these alterations attenuated by treatment. Myocardial expression 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), marker stress, cytokines tumour necrosis factor‐α (TNF‐α), interleukin‐1β interleukin‐6, phosphorylated RIPK1 (p‐RIPK1), p‐RIPK3 p‐MLKL, reflective their respective kinase activities, markers necroptosis, was markedly increased group, increase abolished Similarly, intracellular levels reactive oxygen species, cytokines, p‐RIPK1, p‐MLKL protein H9C2 cardiomyocytes under mimic ischaemia prevented Conclusion Implications leading improvement remodelling function failure.

Language: Английский

The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: May 22, 2025

Abstract Immune system plays a crucial role in the physiological and pathological regulation of cardiovascular system. The exploration history milestones immune diseases (CVDs) have evolved from initial discovery chronic inflammation atherosclerosis to large-scale clinical studies confirming importance anti-inflammatory therapy treating CVDs. This progress has been facilitated by advancements various technological approaches, including multi-omics analysis (single-cell sequencing, spatial transcriptome et al.) significant improvements immunotherapy techniques such as chimeric antigen receptor (CAR)-T cell therapy. Both innate adaptive immunity holds pivotal CVDs, involving Toll-like (TLR) signaling pathway, nucleotide-binding oligomerization domain-containing proteins 1 2 (NOD1/2) inflammasome RNA DNA sensing well antibody-mediated complement-dependent systems. Meanwhile, responses are simultaneously regulated multi-level regulations epigenetics (DNA, RNA, protein) other key pathways interactions among cells, between cardiac or vascular cells. Remarkably, based on basic research system, also made pre-clinical immunotherapy. review provides an overview providing in-depth insights into highlighting impact Finally, we discuss strategies targeting translational implications

Language: Английский