circ_SMG6 may exacerbate MIRI through TLR4/mTOR-associated inflammatory and apoptotic signaling in cardiomyocytes, while sevoflurane attenuates myocardial injury, at least in part, by suppressing this circ_SMG6-related pathway.
MIRI increased myocardial apoptotic index, infarct size, and structural cardiac damage with elevated circ_SMG6 and TLR4/mTOR signaling in rats.
Sevoflurane treatment lessened MIRI-induced increases in apoptotic index, infarct size, structural cardiac damage, circ_SMG6 expression, and TLR4/mTOR signaling, although these were not entirely restored.
Hypoxia-reoxygenation (H/R) increased circ_SMG6 expression, activated TLR4/mTOR signaling, reduced cell viability, and increased TNF-α/IL-1β/IL-6 production in human cardiomyocyte cell lines.
circ_SMG6 knockdown reversed H/R-induced reductions in viability, inflammatory cytokine production, and TLR4/mTOR signaling activation in human cardiomyocytes.
circ_SMG6 overexpression further aggravated H/R-induced injury, including worsened viability, increased inflammatory cytokines, and enhanced TLR4/mTOR signaling.
Sevoflurane treatment phenocopied circ_SMG6 silencing at both functional and signaling levels in H/R-injured human cardiomyocytes.
circ_SMG6 is identified as a potential therapeutic target in sevoflurane-based cardioprotection against MIRI.
This research suggests that a circular RNA molecule called circ_SMG6 plays a harmful role in heart muscle damage that occurs when blood flow is restored after a heart attack — a process known as myocardial ischemia-reperfusion injury (MIRI). Using both rat models of MIRI and human heart muscle cells deprived of oxygen and then reoxygenated (mimicking what happens during a heart attack and its treatment), the study found that circ_SMG6 levels rise during this injury, and that this increase amplifies inflammation and cell death through a signaling pathway involving proteins called TLR4 and mTOR. When circ_SMG6 was artificially reduced in heart cells, injury was lessened; when it was increased, injury was worsened. The study also examined sevoflurane, an anesthetic gas known to have heart-protective properties. The researchers found that sevoflurane reduced circ_SMG6 levels in injured heart cells and in rat hearts after MIRI, and that its protective effects closely mirrored what happened when circ_SMG6 was silenced — including reduced inflammation (lower TNF-α, IL-1β, and IL-6 levels), improved cell survival, and reduced cell death. While sevoflurane did not completely reverse MIRI damage, it significantly lessened it. This research suggests that circ_SMG6 could be a novel target for protecting the heart during and after heart attacks, and that part of sevoflurane's well-known cardioprotective effect may work through suppressing this circular RNA. These findings open the door to future research into whether targeting circ_SMG6 directly — or using sevoflurane strategically during cardiac procedures — could improve outcomes for patients suffering from heart attacks or undergoing cardiac surgery.
Feng M, Li W, Chen B, Sun Y. (2026). Sevoflurane suppresses circ_SMG6 to inhibit TLR4/mTOR signaling and attenuate myocardial ischemia-reperfusion injury.. Molecular biology reports. https://doi.org/10.1007/s11033-026-12758-y