Untargeted metabolomics identifies indole-3-propionic acid to relieve Ang II-induced endothelial dysfunction in aortic dissection.

Indole-3-propionic acid (IPA), a gut microbiota-derived metabolite of tryptophan, has been proven to fulfill an essential function in cardiovascular disease (CVD) and nerve regeneration disease. However, the role of IPA in aortic dissection (AD) has not been revealed. We aimed to investigate the role of IPA in the pathogenesis of AD and the underlying mechanisms of IPA in endothelial dysfunction. Untargeted metabolomics has been employed to screen the plasma metabolic profile of AD patients in comparison with healthy individuals. Network pharmacology provides insights into the potential molecular mechanisms underlying IPA. 3-aminopropionitrile fumarate (BAPN) and angiotensin II (Ang II) were administered to induce AD in mice, while human umbilical vein endothelial cells (HUVECs) were employed for in vitro validation of the signaling pathways predicted by network pharmacology. A total of 224 potentially differential plasma metabolites were identified in the AD patients, with 110 up-regulated metabolites and 114 down-regulated metabolites. IPA was the most significantly decreased metabolite involved in tryptophan metabolism. Bcl2, caspase3, and AKT1 were predicted as the target genes of IPA by network pharmacology and molecular docking. IPA suppressed Ang II-induced apoptosis, intracellular ROS generation, inflammation, and endothelial tight junction (TJ) loss. Animal experiments demonstrated that administration of IPA alleviated the occurrence and severity of AD in mice. Taken together, we identified a previously unexplored association between tryptophan metabolite IPA and AD, providing a novel perspective on the underlying mechanism through which IPA mitigates endothelial dysfunction to protect against AD.

Targeting metabolism in aortic aneurysm and dissection: from basic research to clinical applications.

Aortic aneurysm and dissection (AAD) are a group of insidious and lethal cardiovascular diseases that characterized by seriously threatening the life and health of people, but lack effective nonsurgical interventions. Alterations in metabolites are increasingly recognized as universal features of AAD because metabolic abnormalities have been identified not only in arterial tissue but also in blood and vascular cells from both patients and animal models with this disease. Over the past few decades, studies have further supported this notion by linking AAD to various types of metabolites such as those derived from gut microbiota or involved in TCA cycle or lipid metabolism. Many of these altered metabolites may contribute to the pathogenesis of AAD. This review aims to illustrate the close association between body metabolism and the occurrence and development of AAD, as well as summarize the significance of metabolites correlated with the pathological process of AAD. This provides valuable insight for developing new therapeutic agents for AAD. Therefore, we present a brief overview of metabolism in AAD biology, including signaling pathways involved in these processes and current clinical studies targeting AAD metabolisms. It is necessary to understand the metabolic mechanisms underlying AAD to provides significant knowledge for AAD diagnosis and new therapeutics for treatment.

Incidence and risk factors of recurrent pain in acute aortic dissection and in-hospital mortality.

BACKGROUND: We investigated the prevalence of recurrent pain and its relationship with in-hospital mortality in acute aortic dissection (AAD). PATIENTS AND METHODS: Between 2011 and 2016, 234 AAD patients were selected. Recurrent pain was defined as a mean of VAS > 3, within 48 hours following hospital admission or before emergency operation. Patients with and without recurrent pain were divided into group I and group II, respectively into type A AAD and type B AAD patients. Our primary outcome was in-hospital mortality. RESULTS: The incidence of recurrent pain was 24.4 % in AAD patients. Incidence of recurrent pain was higher in type A AAD patients than type B AAD patients (48.9 vs. 9.6 %). Overall in-hospital mortality was 25.6 %. Type A AAD had a higher in-hospital mortality than type B AAD patients (47.7 vs. 12.3 %). Group I had significantly higher in-hospital mortality than group II (type A: 79.1 vs. 17.8 %; type B: 57.1 vs. 7.6 %, all P < 0.001), as was the case with medical managed patients (type A: 72.1 vs. 13.3 %; type B: 35.7 vs. 2.3 %, all P < 0.001). Logistic regression analysis showed that use of one drug alone and waist pain were predictive factors for recurrent pain in type A AAD and type A AAD patients, respectively (OR 3.686, 95 % CI: 1.103~12.316, P = 0.034 and OR 14.010, 95 % CI: 2.481~79.103, P = 0.003). Recurrent pains were the risk factors (type A: OR 11.096, 95 % CI: 3.057~40.280, P < 0.001; type B: OR 14.412, 95 % CI: 3.662~56.723, P < 0.001), while invasive interventions were protective (type A: OR 0.133, 95 % CI: 0.035~0.507, P < 0.001; type B: OR 0.334, 95 % CI: 0.120~0.929, P = 0.036) for in-hospital mortality in AAD patients. CONCLUSIONS: Approximately one-fourth of AAD patients presented with recurrent pains, which might increase in-hospital mortality. Thus, interventional strategies at early stages are important.

An assessment of platelet parameters in different ethnic groups with hypertension subtypes and associated risk factors in Xinjiang, China.

The goal of this study was to investigate platelet parameters in populations with hypertension subtypes among the Han, Uygur, and Kazakh ethnic groups and their associated risk factors in Xinjiang, northwestern China. In total, 9816 adult participants were recruited from a multiethnic, cross-sectional cardiovascular risk survey. Our results indicated that the platelet counts in Han, Uygur, and Kazakh participants with isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic diastolic hypertension (SDH) varied significantly (P < 0.001). Additionally, the mean platelet volume (MPV) in Han, Uygur, and Kazakh participants with ISH was significantly different (P < 0.05). Furthermore, the individual platelet parameters had different associated risk factors. For example, the risk factors for platelet counts were Uygur ethnicity, Kazakh ethnicity, drinking, ISH, diabetes, and high triglycerides (TGs). The risk factors for MPV were Uygur ethnicity, smoking, overweight, obesity, ISH, IDH, diabetes, and high TGs. Gender was a risk factor for abnormal plateletcrit (PCT) values. Only a low high-density lipoprotein cholesterol level was found to be a risk factor for platelet distribution width (PDW). We suggest that more attention should be paid to platelet parameters and the associated risk factors to reinforce the effect of antiplatelet therapy and to provide a clinical basis for preventing the occurrence of thrombosis complications and cerebro- and cardiovascular diseases effectively.

Association of genetic variations in the lipid regulatory pathway genes FBXW7 and SREBPs with coronary artery disease among Han Chinese and Uygur Chinese populations in Xinjiang, China.

BACKGROUND: Hyperlipidemia is a major risk factor for coronary artery disease (CAD). The current study was designed to explore the possible correlation between single nucleotide polymorphisms (SNPs) in the lipid homeostasis regulatory genes F-box and WD repeat domain-containing 7 (FBXW7) and sterol regulatory element-binding proteins (SREBPs) with CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China. RESULTS: In the Uygur Chinese population, rs9902941 in SREBP-1 and rs10033601 in FBXW7 were found to be associated with CAD in a recessive model (TT vs. CT + CC, P = 0.032; GG vs. AG + AA, P = 0.010, respectively), and rs7288536 in SREBP-2 was found to be associated with CAD in an additive model (CT vs. CC + TT, P = 0.045). The difference was statistically significant in the Uygur Chinese population after multivariate adjustments [Odds ratio (OR) = 1.803, 95% confidence interval (CI): 1.036~3.137, P = 0.037; OR = 1.628, 95% CI: 1.080~2.454, P = 0.020; OR = 1.368; and 95% CI: 1.018~1.837, P = 0.037, respectively]. There were also significant interactions between the above-mentioned models in the Uygur Chinese population. However, these relationships were not observed before or after multivariate adjustment in the Han Chinese population. MATERIALS AND METHODS: A total of 1,312 Han Chinese (650 CAD patients and 662 controls) and 834 Uygur Chinese (414 CAD patients and 420 controls) were enrolled in this case-control study. Three SNPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) were selected and genotyped using the improved multiplex ligase detection reaction (iMLDR) method. CONCLUSIONS: The results of this study indicate that variations in the lipid regulatory pathway genes FBXW7 and SREBPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) are associated with CAD in the Uygur Chinese population in Xinjiang, China.

Association of lipid metabolism relevant gene FBXW7 polymorphism with coronary artery disease in Uygur Chinese population in Xinjiang, China: a case-control.

BACKGROUND: Hyperlipidemia is a major risk factor for coronary artery disease (CAD). As F-box and WD repeat domain-containing 7 (FBXW7) gene is an important regulating factor for lipid metabolism, the aim of the present study is to assess the association between human FBXW7 gene polymorphisms and CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China. METHODS: A total of 1,312 Han Chinese (650 CAD patients and 662 controls) and 834 Uygur Chinese (414 CAD patients and 420 controls) were enrolled in this case-control study. Three single nucleotide polymorphisms (SNPs) rs2255137 T>C, rs2292743 A>T, rs35311955 G>C of FBXW7 were selected and genotyped using the improved multiplex ligase detection reaction (iMLDR) method. RESULTS: We found that the rs2255137 CC genotype was very common in the CAD patients compared with the control subjects in the Uygur Chinese populations. After adjustments for several confounders: age, gender, smoking, drinking, hypertension, diabetes, TG, TC, HDL-C and LDL-C, this association remained significant. Furthermore, we investigated the relationships between rs2255137 genotypes and the circulating serum lipid levels and found that people carrying the C allele of rs2255137 may have higher serum lipid levels in the Uygur Chinese populations. CONCLUSION: Our results indicate that rs2255137 in FBXW7 gene is associated with CAD in the Uygur Chinese population in China.