Metabolic Profiling in Association with Vascular Endothelial Cell Dysfunction Following Non-Toxic Cadmium Exposure.

This study aimed to determine the metabolic profile of non-toxic cadmium (Cd)-induced dysfunctional endothelial cells using human umbilical vein endothelial cells (HUVECs). HUVECs (n = 6 per group) were treated with 0, 1, 5, or 10 µM cadmium chloride (CdCl2) for 48 h. Cell phenotypes, including nitric oxide (NO) production, the inflammatory response, and oxidative stress, were evaluated in Cd-exposed and control HUVECs. Cd-exposed and control HUVECs were analysed using gas chromatography time-of-flight/mass spectrometry. Compared to control HUVECs, Cd-exposed HUVECs were dysfunctional, exhibiting decreased NO production, a proinflammatory state, and non-significant oxidative stress. Further metabolic profiling revealed 24 significantly-altered metabolites in the dysfunctional endothelial cells. The significantly-altered metabolites were involved in the impaired tricarboxylic acid (TCA) cycle, activated pyruvate metabolism, up-regulated glucogenic amino acid metabolism, and increased pyrimidine metabolism. The current metabolic findings further suggest that the metabolic changes linked to TCA cycle dysfunction, glycosylation of the hexosamine biosynthesis pathway (HBP), and compensatory responses to genomic instability and energy deficiency may be generally associated with dysfunctional phenotypes, characterized by decreased NO production, a proinflammatory state, and non-significant oxidative stress, in endothelial cells following non-toxic Cd exposure.

Studies on the Anti-Inflammatory Effect of Xiaoyao Pills in The Treatment of Postmenopausal Osteoporosis in Mice.

Osteoporosis is a common metabolic disease of elderly and postmenopausal women, with no obvious symptoms during its early stages. In the latter stages of this condition, the patients are prone to fractures, and this can seriously affect their health and quality of life. The worldwide increase in life expectancy has made osteoporosis a global concern. The Xiaoyao pills were previously used in the treatment of depression. In addition, the drug appeared to have estrogen-like activity, which affected the expression of ALP, an early osteoblast-specific marker, and COL-1, a major component of bone extracellular matrix. Xiaoyao pills were assessed for their effects on postmenopausal osteoporosis (PMOM) in mice. The target information of each herbal component of Xiaoyao pills was accessed through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Information from GeneCards, OMIM, PharmGkb, TTD, DrugBank, and other websites was used to construct the regulatory network of the herbal complex through Cytoscape and String network to assess the protein interactions. Mice were ovariectomized, and treated with high and low doses of Xiaoyao pills and these were compared to controls. Their symptoms were assessed by immunocytochemistry of bone tissues. The results suggested that Xiaoyao pills had the ability to alleviate the symptoms of PMOM in ovariectomized mice through the IL-17 signaling pathway. This drug has the potential to become a novel therapeutic agent for the treatment of osteoporosis.

Metabolic profiling reveals the heterogeneity of vascular endothelial function phenotypes in individuals at extreme cardiovascular risk.

Maladapted vascular endothelial metabolism in the context of endothelial function differing in phenotype remains unknown, which limits our understanding of the heterogeneous pathogenesis of atherosclerotic cardiovascular disease (CVD). This study aimed to profile serum metabolic alterations of different vascular endothelial function phenotypes in asymptomatic adults at extreme cardiovascular risk. In addition to 12 CVD patients, 103 individuals free of CVD were categorized as having normal endothelial function (NEF) (n = 30), cardiovascular risk-promoting endothelial function (PEF) (n = 18), cardiovascular risk-resistant endothelial function (REF) (n = 25), and vulnerable endothelial function (VEF) (n = 30). Serum metabolic profiles were detected using gas chromatography time-of-flight/mass spectrometry and multivariate statistics. Compared to the NEF group, a total of 17, 17, 22, and 13 differential metabolites were identified in the PEF, REF, VEF, and CVD groups, respectively. Of the altered metabolic pathways, multiple pathways were consistent between the PEF and CVD groups, including pyrimidine metabolism, starch and sucrose metabolism, aminoacyl-tRNA biosynthesis, arginine and proline metabolism, and d-glutamine and d-glutamate metabolism. Notably, a relative increase in low-calorie sugar in galactose metabolism was exclusively found in the REF group, and a relative increase in the ratio of acetyl-CoA to CoA was suggested in the VEF group based on elevated butanoate metabolism and reduced pantothenate and CoA biosynthesis. Our findings clearly indicate distinct metabolic patterns across groups with heterogeneous vascular endothelial function in the context of extreme cardiovascular risk, and improve our understanding of the pathogenic heterogeneity of early CVD in asymptomatic populations.

Association of Impaired Vascular Endothelial Function with Increased Cardiovascular Risk in Asymptomatic Adults.

Impaired vascular endothelial function has attracted attention as a prognostic indicator of cardiovascular prevention. The association between impaired endothelial function and cardiovascular risk in the asymptomatic population, however, has been poorly explored. We evaluated the association of brachial artery flow-mediated dilation (FMD) with Framingham-estimated 10-year cardiovascular disease (CVD) risk in subjects free of CVD, especially by cardiovascular risk profiles. In total, 680 adults aged 30-74 years were enrolled from Rongan and Rongshui of Liuzhou, Guangxi, China, through a cross-sectional study in 2015. In the full-adjusted model, the odds ratio for the estimated 10-year CVD risk comparing the low FMD (<6%) with the high FMD (≥10%) was 2.81 (95% confidence interval [CI]: 1.21, 6.53; P for trend = 0.03). In subgroup analyses, inverse associations between FMD and the estimated 10-year CVD risk were found in participants with specific characteristics. The adjusted odds ratios, comparing the 25th and the 75th percentiles of FMD, were 2.77 (95% CI: 1.54, 5.00) for aged ≥60 years, 1.77 (95% CI: 1.16, 2.70) for female, 1.59 (95% CI: 1.08, 2.35) for nonsmokers, 1.74 (95% CI: 1.02, 2.97) for hypertension, 1.59 (95% CI: 1.04, 2.44) for normal glycaemia, 2.03 (95% CI: 1.19, 3.48) for C-reactive protein ≥10 mg/L, and 1.85 (95% CI: 1.12, 3.06) for eGFR <106 mL/minute per 1.73 m2. Therefore, impaired endothelial function is associated with increased CVD risk in asymptomatic adults. This inverse association is more likely to exist in subjects with higher cardiovascular risk.