NLRP3 Inflammasome May Be a Biomarker for Risk Stratification in Patients with Acute Coronary Syndrome.

Purpose: Acute coronary syndrome (ACS) has a high incidence and mortality rate worldwide, which has a considerable negative impact on the global economy. This study aimed to identify a group of ACS patients at a high risk of recurrent adverse cardiac events using the plasma NLRP3 inflammasome. Patients and methods: ACS patients admitted to Liaocheng People's Hospital between June 2021 and March 2022 were enrolled in this study. Patients were divided into low (levels < 3.84 ng/mL) and high (levels ≥ 3.84 ng/mL) groups based on the median NLRP3 inflammasome levels. The patients were divided into three groups according to the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P): low (scores ≤ 2 points), intermediate (scores = 3 points), and high (score ≥ 4 points) risk. We investigated the relationship between NLRP3 inflammasome and laboratory indicators. Additionally, we examined whether the NLRP3 inflammasome was an independent predictor of high TRS-2P and explored the applicability of the plasma NLRP3 inflammasome for predicting high TRS-2P. Results: Logistic regression analysis revealed that NLRP3 inflammasome was an independent predictor of high TRS-2P (odds ratio [OR]:2.013; 95% confidence interval [CI]: 1.174-3.452). The area under the receiver operating characteristic curve value of the NLRP3 inflammasome was 0.674 (95% CI: 0.611-0.737; P < 0.001). Conclusion: NLRP3 inflammasome levels are an independent predictive factor for high TRS-2P levels, which indicates that the NLRP3 inflammasome may help predict the prognosis of ACS patients.

Leukocyte telomere length: a potential biomarker for the prognosis of coronary artery disease.

Aim: This study aimed to explore the prognostic value of leukocyte telomere length (LTL) in patients with coronary artery disease (CAD). Materials & methods: We enrolled 366 CAD patients and 76 healthy subjects in this study. LTL was measured. All subjects were followed up for 6 months for further analysis regarding major adverse cardiac events (MACEs). Results: CAD patients had a significantly shortened LTL compared with healthy subjects (p < 0.05). The area under the curve for LTL prediction of MACEs was 0.769 (p < 0.001), with a shorter LTL being an independent predictor of MACEs (Cox proportional hazards regression, hazard ratio: 2.866; p < 0.001). Conclusion: LTL could be considered as an independent predictor of short-term MACEs in CAD.

HMGB1 Protects the Heart Against Ischemia-Reperfusion Injury via PI3K/AkT Pathway-Mediated Upregulation of VEGF Expression.

Delivery of exogenous high mobility group box 1 (HMGB1) may exert a beneficial effect on myocardial ischemia-reperfusion (I/R) injury. Since the expression of vascular endothelial growth factor (VEGF) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in the myocardium mediates the cardioprotective function of basic fibroblast growth factor, we hypothesized that VEGF and the PI3K/Akt signaling pathway also mediate the protective effects of intravenously delivered HMGB1. Thus, the objective of the present study was to analyze the impact of intravenous administration of HMGB1 on the myocardial expression of VEGF, myocardial fibrosis, and cardiac function in rats subjected to acute myocardial I/R. The ischemia was induced by ligation of the left anterior descending coronary artery for 30 min and was followed by 3 h of reperfusion. Myocardial malondialdehyde content, infarct size, and collagen volume fraction decreased, while the activity of superoxide dismutase was increased, the expression of VEGF and p-Akt was upregulated, and cardiac function was improved in the HMGB1-treated group when compared with rats subjected to I/R only (all P < 0.05). However, these effects of HMGB1 were abolished by LY294002. The obtained results demonstrate that the cardioprotective effects of intravenous administration of HMGB1 prior to I/R may be mediated by upregulation of myocardial expression of VEGF, which may activate the PI3K/Akt signaling pathway.

High mobility group box 1 protein attenuates myocardial ischemia reperfusion injury via inhibition of the p38 mitogen-activated protein kinase signaling pathway.

The present study aimed to determine the effects of high mobility group box 1 protein (HMGB1) on myocardial ischemia reperfusion (I/R) injury in rats following acute myocardial ischemia and investigate the underlying molecular mechanisms of these effects. Male Wistar rats were randomly divided into the following groups (n=10/group): Sham operation; I/R; HMGB50 (50 ng/kg HMGB1 before I/R); HMGB100 (100 ng/kg HMGB1 before I/R); and HMGB200 (200 ng/kg HMGB1 before I/R). Serum cardiac troponin I (cTnI), interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were subsequently measured. Myocardial levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were also determined. Myocardial infarction size (IS) was determined by 2,3,5-triphenyltetrazolium chloride staining. Myocardial expression of hypoxia inducible factor (HIF)-1α and phosphorylated p38 mitogen-activated protein kinase (P-p38 MAPK) protein was measured using western blotting. The results demonstrated that HMGB1 significantly decreased serum levels of cTnI, IL-6 and TNF-α and myocardial IS in I/R rats compared with the sham group (all P<0.05). HMGB1 also significantly decreased and increased myocardial levels of MDA and SOD, respectively (both P<0.05). HMGB1 significantly increased myocardial expression of HIF-1α and decreased expression of P-p38 MAPK following I/R (both P<0.05). These effects of HMGB1 occurred in a dose-dependent manner. The results of the current study indicate that the cardioprotective effects of intravenous HMGB1 are associated with increased myocardial expression of HIF-1α via inhibition of P-p38 MAPK expression, leading to inhibition of the P-p38 MAPK signaling pathway.

Intravenous high mobility group box 1 upregulates the expression of HIF-1α in the myocardium via a protein kinase B-dependent pathway in rats following acute myocardial ischemia.

The effects of intravenous high mobility group box 1 (HMGB1) on myocardial ischemia/reperfusion (I/R) injury remains to be elucidated. The purpose of the present study was to investigate the effects of intravenous HMGB1 on the expression of hypoxia inducible factor-1α (HIF-1α) in the myocardium of rats following acute myocardial ischemia, and to examine the effects of intravenous HMGB1 on myocardial I/R injury. Male Wistar rats were divided into the following groups: Sham operation group (n=10), a group exposed to ischemia for 30 min and reperfusion for 4 h (I/R group) as a control (n=10), an HMGB group, in which 100 ng/kg HMGB was administered intravenously 30 min prior to ischemia (n=10), an LY group, in which LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), was administered intravenously (0.3 mg/kg) 40 min prior to ischemia (n=10), and the HMGB1+LY group, in which HMGB1 (100 ng/kg) and LY294002 (0.3 mg/kg) were administered intravenously 30 min and 40 min prior to ischemia, respectively (n=10). The serum levels of cardiac troponin I (cTnI) and tumor necrosis factor-α (TNF-α), and myocardial infarct size were measured. The expression levels of phosphorylated Akt and HIF-1α were investigated using western blot analyses. The results showed that pre-treatment with HMGB1 significantly decreased serum levels of cTnI, and TNF-α, and reduced myocardial infarct size following 4 h reperfusion (all P<0.05). HMGB1 also increased the expression levels of HIF-1α and p-Akt induced by I/R (P<0.05). LY294002 was found to eliminate the effects of intravenous HMGB1 on myocardial I/R injury (P<0.05). These results suggest that intravenous pre-treatment with HMGB1 may exert its cardioprotective effects via the upregulation of the myocardial expression of HIF-1α, which may be regulated by the PI3K/Akt signaling pathway, in rats following acute myocardial I/R.

Postconditioning with simvastatin decreases myocardial injury in rats following acute myocardial ischemia.

The aim of the present study was to investigate whether postconditioning with simvastatin attenuated myocardial ischemia reperfusion injury by inhibiting the expression of high mobility group box 1 (HMGB1) in rat myocardium following acute myocardial ischemia. In total, 30 male Sprague-Dawley rats were divided into sham operation (sham; n=10), acute myocardial infarction (AMI; n=10) and simvastatin (sim; n=10) groups. The AMI and sim groups were subjected to ischemia for 30 min, followed by reperfusion for 180 min. The rats in the sim group were administered 20 mg/kg simvastatin intravenously 5 min prior to reperfusion. Subsequently, the infarct size, serum cardiac troponin (c-TnI), tumor necrosis factor (TNF)-α and myocardial malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. Western blot analysis was used to detect the protein expression of HMGB1. Postconditioning with simvastatin was shown to decrease the infarct size and HMGB1 expression levels in the myocardium following AMI (P<0.05). In addition, postconditioning with simvastatin not only decreased the serum levels of c-TnI and TNF-α (P<0.05), but also inhibited the increase in MDA levels and the reduction in SOD activity (P<0.05). Therefore, postconditioning with simvastatin was shown to attenuate myocardial injury. The underlying mechanism may be associated with the downregulation of HMGB1 expression in the ischemic myocardium.