Background: The triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and triglyceride-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute indicators for insulin resistance (IR). This study aimed to compare the predictive value of these indicators for 5-year mortality in critically ill patients with chronic heart failure (CHF). Methods: Critically ill patients with CHF were identified from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) III and IV databases. The primary outcome was 5-year mortality. The relationship between the three indices and mortality risk was determined using multivariate Cox proportional hazards models, Kaplan–Meier (K‒M) analysis and restricted cubic splines analysis. A receiver operating characteristic (ROC) curve was generated to compare the ability of the three indices to predict mortality. Finally, whether the IR indices would further increase the predictive ability of the basic model including baseline variables with a significance level between survivors and non-survivors was evaluated by ROC curve. Results: Altogether, 1329 patients with CHF were identified from the databases. Cox proportional hazards models indicated that the TyG index was independently associated with an elevated risk of 5-year mortality (hazard ratio [HR], 1.56; 95% confidence interval [CI] 1.29–1.9), while the TyG-BMI index and TG/HDL-C level were significantly associated with 5-year mortality, with an HR (95% CI) of 1.002 (1.000–1.003) and 1.01 (1.00–1.03), respectively. The K–M analysis revealed that the cumulative incidence of all-cause 5-year death increased with increasing quartiles of the TyG index, TyG-BMI index, or TG/HDL-C ratio. According to the ROC curve, the TyG index outperformed the TyG-BMI and TG/HDL-C ratio at predicting all-cause 5-year mortality (0.608 [0.571–0.645] vs. 0.558 [0.522–0.594] vs. 0.561 [0.524–0.598]). The effect of the TyG index on all-cause mortality was consistent across subgroups, with no significant interaction with randomized factors. Furthermore, adding the TyG index to the basic model for 5-year mortality improved its predictive ability (area under the curve, 0.762 for the basic model vs. 0.769 for the basic model + TyG index); however, the difference was not statistically significant. Conclusion: As continuous variables, all three indices were significantly associated with 5-year mortality risk in critically ill patients with CHF. Although these IR indices did not improve the predictive power of the basic model in patients with CHF, the TyG index appears to be the most promising index (vs. TyG-BMI and TG/HDL-C ratio) for prevention and risk stratification in critically ill patients with CHF.

Background: Prior research has established the correlation between insulin resistance (IR) and hypertension. While the association between triglyceride-glucose (TyG) index, a reliable surrogate marker of IR, and uncontrolled hypertension as well as arterial stiffness among individuals with hypertension remains undisclosed. Methods: In this study, a total of 8513 adults diagnosed with hypertension from the National Health and Nutrition Examination Survey 1999–2018 were included. The primary outcome of the study are arterial stiffness (represented with estimated pulse wave velocity, ePWV) and uncontrolled hypertension. Logistic regression model, subgroup analysis, restricted cubic spine, and smooth curve fitting curve were conducted to evaluate the association between the IR indicators and uncontrolled hypertension and arterial stiffness in individuals with hypertension. Results: Among included participants, the overall prevalence of uncontrolled hypertension was 54.3%. After adjusting for all potential covariates, compared with the first quartile of TyG index, the risk of uncontrolled hypertension increased about 28% and 49% for participants in the third quartile (OR, 1.28; 95% CI 1.06–1.52) and the fourth quartile (OR, 1.49; 95% CI 1.21–1.89) of TyG index, respectively. The higher OR of TyG index was observed in participants taking antihypertensive medication [fourth quartile versus first quartile (OR, 2.03; 95% CI 1.37–3.11)]. Meanwhile, we explored the potential association between TyG index and arterial stiffness and found that TyG index was significantly associated with increased arterial stiffness (β for ePWV, 0.04; 95% CI 0.00–0.08; P = 0.039). However, traditional IR indicator HOMA-IR showed no significant positive correlation to uncontrolled hypertension as well as arterial stiffness in US adults with hypertension. Conclusion: Elevated levels of the TyG index were positive associated with prevalence of uncontrolled hypertension and arterial stiffness among US adults with hypertension.

Background: Hydrogen peroxide (H ₂ O ₂ ) is a critical molecular signal in the development of abdominal aortic aneurysm ( AAA ) formation. Vascular peroxidase 1 ( VPO 1) catalyzes the production of hypochlorous acid ( HOC l) from H ₂ O ₂ and significantly enhances oxidative stress. The switch from a contractile phenotype to a synthetic one in vascular smooth muscle cells ( VSMC s) is driven by reactive oxygen species and is recognized as an early and important event in AAA formation. This study aims to determine if VPO 1 plays a critical role in the development of AAA by regulating VSMC phenotypic switch. Methods and Results: VPO 1 is upregulated in human and elastase‐induced mouse aneurysmal tissues compared with healthy control tissues. Additionally, KLF 4, a nuclear transcriptional factor, is upregulated in aneurysmatic tissues along with a concomitant downregulation of differentiated smooth muscle cell markers and an increase of synthetic phenotypic markers, indicating VSMC phenotypic switch in these diseased tissues. In cultured VSMC s from rat abdominal aorta, H ₂ O ₂ treatment significantly increases VPO 1 expression and HOC l levels as well as VSMC phenotypic switch. In support of these findings, depletion of VPO 1 significantly attenuates the effects of H ₂ O ₂ and HOC l treatment. Furthermore, HOC l treatment promotes VSMC phenotypic switch and ERK 1/2 phosphorylation. Pretreatment with U0126 (a specific inhibitor of ERK 1/2) significantly attenuates HOC l‐induced VSMC phenotypic switch. Conclusions: Our results demonstrate that VPO 1 modulates VSMC phenotypic switch through the H ₂ O ₂ / VPO 1/ HOC l/ ERK 1/2 signaling pathway and plays a key role in the development of AAA . Our findings also implicate VPO 1 as a novel signaling node that mediates VSMC phenotypic switch and plays a key role in the development of AAA . Clinical Trial Registration: URL : www.chictr.org.cn . Unique identifier: Chi CTR 1800016922.

Reactive oxygen species (ROS) play essential roles in the pulmonary vascular remodelling associated with hypoxia-induced pulmonary hypertension (PH). Vascular peroxidase 1 (VPO1) is a newly identified haeme-containing peroxidase that accelerates oxidative stress development in the vasculature. This study aimed to determine the potential role of VPO1 in hypoxia-induced PH-related vascular remodelling. The vascular morphology and VPO1 expression were assessed in the pulmonary arteries of Sprague–Dawley (SD) rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and VPO1 expression and HOCl production were significantly increased in hypoxic rats, which also exhibited obvious vascular remodelling. Furthermore, a hypoxia-induced PH model was generated by exposing primary rat pulmonary artery smooth muscle cells (PASMCs) to hypoxic conditions (3% O₂, 48 h), which significantly increased the expression of NOX4 and VPO1 and the production of HOCl. These hypoxic changes were accompanied by enhanced proliferation, apoptosis resistance, and migration. In PASMCs, hypoxia-induced changes, including effects on the expression of cell cycle regulators (cyclin B1 and cyclin D1), apoptosis-related proteins (bax, bcl-2, and cleaved caspase-3), migration promoters (matrix metalloproteinases 2 and 9), and NF-κB expression, as well as the production of HOCl, were all inhibited by silencing VPO1 with small interfering RNAs. Moreover, treatment with HOCl under hypoxic conditions upregulated NF-κB expression and enhanced proliferation, apoptosis resistance, and migration in PASMCs, whereas BAY 11-7082 (an inhibitor of NF-κB) significantly inhibited these effects. Collectively, these results demonstrate that VPO1 promotes hypoxia-induced proliferation, apoptosis resistance, and migration in PASMCs via the NOX4/VPO1/HOCl/NF-κB signalling pathway.

Selenium was one of the essential trace elements that played a pivotal role in human health. Although previous studies have investigated the relationship between selenium and non-alcoholic fatty li...

Reactive oxygen species (ROS) derived from NADPH oxidases (NOX) plays an essential role in advanced glycation end products (AGEs)-induced diabetic vascular endothelial dysfunction. Peroxidasin (PXDN, VPO1) is one member of peroxidases family that catalyzes hydrogen peroxide (H₂O₂) to hypochlorous acid (HOCl). This present study aimed to elucidate the role of PXDN in promoting vascular endothelial dysfunction induced by AGEs in diabetes mellitus. We found that, compared to non-diabetic (db/m) mice, PXDN expression was notably increased in db/db mice with impaired endothelium-dependent relaxation. Knockdown of PXDN in vivo through tail vein injection of siRNA restored the impaired endothelium-dependent relaxation function of db/db mice which is accompanied with up-regulation of eNOS Ser1177 phosphorylation and NO production. AGEs significantly elevated expression of PXDN and 3-Cl-Tyr, but decreased phosphorylation of Akt and eNOS and NO release in HUVECs. All these effects induced by AGEs were remarkable alleviated by silencing PXDN with small interfering RNAs. In addition, HOCl treatment alone as well as HOCl added with Akt inhibitor MK2206 inhibited phosphorylation of Akt and eNOS, reducing NO production. More importantly,AGEs-induced up-regulation of PXDN and 3-Cl-Tyr with endothelial dysfunction were transformed by NOX2 silencing and H₂O₂ scavengers. Thus, these results support the conclusion that PXDN promotes AGEs-induced diabetic vascular endothelial dysfunction by attenuating eNOS phosphorylation at Ser1177 via NOX2/HOCl/Akt pathway.