Background: To investigate the effect of visit-to-visit fasting plasma glucose (FPG) variability on the left cardiac structure and function in patients with type 2 diabetes mellitus (T2DM). Methods: In this prospective cohort study, 455 T2DM patients were included and follow-up for a median of 4.7 years. FPG measured on every hospital visit was collected. FPG variability was calculated by its coefficient of variation (CV-FPG). Left cardiac structure and function were assessed using echocardiography at baseline and after follow-up. Multivariable linear regression analyses were used to estimate the effect of FPG variability on the annualized changes in left cardiac structure and function. Subgroup analysis stratified by mean HbA1c levels (< 7% and ≥ 7%) were also performed. Result: In multivariable regression analyses, CV-FPG was independently associated with the annualized changes in left ventricle (β = 0.137; P = 0.031), interventricular septum (β = 0.215; P = 0.001), left ventricular posterior wall thickness (β = 0.129; P = 0.048), left ventricular mass index (β = 0.227; P < 0.001), and left ventricular ejection fraction (β = − 0.132; P = 0.030). After additionally stratified by mean HbA1c levels, CV-FPG was still independently associated with the annualized changes in the above parameters in patients with HbA1c ≥ 7%, while not in patients with HbA1c < 7%. Conclusions: Visit-to-visit variability in FPG could be a novel risk factor for the long-term adverse changes in left cardiac structure and systolic function in patients with type 2 diabetes. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015, retrospectively registered.

Background: Changes in circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) are considered as a new perspective reflection of the endothelial injury and repair status. Our previous studies have demonstrated that berberine improved endothelial function and arterial stiffness in healthy subjects. In this study, we further investigated the effects of berberine on regulating the circulating EMPs and EPCs, and preventing endothelial dysfunction and arterial stiffness in spontaneously hypertensive rats (SHRs). Methods: Twenty male SHRs were randomly divided into two groups: Berberine-treated SHR group and vehicle-treated SHR group. The SHR rats were intragastrically treated with physiologic saline, berberine 50 mg/kg.d or vehicle for 4 weeks, respectively. Ten male Wistar-Kyoto (WKY) rats treated with vehicle served as normotensive controls. Tail systolic blood pressure was monitored every 2 weeks. At the end of the study, aortic pulse wave velocity (aPWV) was measured in vivo, and aorta were collected for measurement of endothelium-dependent vasodilation and immunohistological staining of elastic fiber. Peripheral blood was collected for circulating EMP detection and EPC culture. Results: Compared to normotensive rats, hypertensive rats displayed significantly higher circulating CD31+/CD42− MPs, lower number and colony-forming units (CFUs) of EPCs, worse endothelium-dependent vasodilation, and faster aPWV. Berberine treatment in SHRs partly reduced the blood pressure and circulating EMPs, and augmented EPC numbers and CFUs. In addition, berberine preserved arterial elasticity by lowering aPWV and increasing the content of arterial media elastin fiber, and improved endothelial function by maintaining better endothelium-dependent vasodilation. Robust relationship was observed among circulating CD31+/CD42− MPs, EPC numbers and aPWV. Conclusions: Abnormal changes of circulating EMPs and EPCs in SHRs are associated with endothelial dysfunction and arterial stiffness. Berberine may be a novel therapeutic option for the hypertension-related vascular injury in SHRs.

Background. Studies show that aliskiren exerts favourable effects not only on endothelial progenitor cells (EPCs) but also on endothelial function. However, the mechanism of the favourable effect of aliskiren on EPCs from patients with hypertension is unclear and remains to be further studied. Methods. The object of this study was to investigate and assess the in vitro function of EPCs pretreated with aliskiren. After treated with aliskiren, the human EPCs were transplanted into a nude mouse model of carotid artery injury, and the in vivo reendothelialization of injured artery was estimated by staining denuded areas with Evans blue dye via tail vein injection. Results. We found that aliskiren increased the in vitro migration, proliferation, and adhesion of EPCs from patients with hypertension in a dose-dependent manner and improved the reendothelialization capability of these EPCs. Furthermore, aliskiren increased the phosphorylation of Tie2, Akt, and eNOS. After the blockade of the Tie2 signalling pathway, the favourable effects of aliskiren on the in vitro function and in vivo reendothelialization capability of EPCs were suppressed. Conclusions. This study demonstrates that aliskiren can improve the in vitro function and in vivo reendothelialization capability of EPCs from patients with hypertension via the activation of the Tie2/PI3k/Akt/eNOS signalling pathway. These findings further indicate that aliskiren is an effective pharmacological treatment for cell-based repair in hypertension-related vascular injury.

Objectives. MicroRNA-125b (miR-125b) has been recognized as one of the key regulators of the inflammatory responses in cardiovascular diseases recently. This study sought to dissect the role of miR-125b in modulating the function of endothelial progenitor cells (EPCs) in the inflammatory environment of ischemic hearts. Methods. EPCs were cultured and transfected with miR-125b mimic and negative control mimic. Cell migration and adhesion assays were performed after tumor necrosis factor-α (TNF-α) treatment to determine EPC function. Cell apoptosis was analyzed by flow cytometry. The activation of the NF-κB pathway was measured by western blotting. EPC-mediated neovascularization in vivo was studied by using a myocardial infarction model. Results. miR-125b-overexpressed EPCs displayed improved cell migration, adhesion abilities, and reduced cell apoptosis compared with those of the NC group after TNF-α treatment. miR-125b overexpression in EPCs ameliorated TNF-α-induced activation of the NF-κB pathway. Mice transplanted with miR-125b-overexpressed EPCs showed improved cardiac function recovery and capillary vessel density than the ones transplanted with NC EPCs. Conclusions. miR-125b protects EPCs against TNF-α-induced inflammation and cell apoptosis by attenuating the activation of NF-κB pathway and consequently improves the cardiac function recovery and EPC-mediated neovascularization in the ischemic hearts.

Purpose: Inflammatory activation of immune cells plays a pivotal role in the development of coronary artery diseases (CAD). This study aims to investigate the immune responses of peripheral blood mononuclear cells (PBMCs) in CAD and to identify novel signature genes and biomarkers using machine learning algorithms. Methods: The GSE113079 dataset was analyzed and differentially expressed genes (DEGs) were identified between CAD and normal samples. The intersection of DEGs with inflammation-related genes was used to identify the differentially expressed inflammation-related genes (DIRGs). Then, the receiver operating characteristic (ROC) curves were plotted for each DIRG, and those with an area under the curve (AUC) greater than 0.9 were selected for subsequent analysis. Furthermore, machine learning algorithms were employed to identify biomarkers. A nomogram was developed based on these biomarkers. The CIBERSORT algorithm and Wilcoxon test method were used to analyze the differences in immune cells between the CAD and normal samples. The identified biomarkers were validated in PBMCs from patients with CAD and in atherosclerotic aortas from ApoE^−/− mice. Results: A total of 574 DEGs were identified between CAD and normal samples. From this intersection, 29 DIRGs were identified, of which 14 DIRGs (PTGER1, IL17RC, KLKB1, GPR32, ADM, NUPR1, SCN9A, IL17B, CX3CL1, FFAR3, PYDC2, SYT11, RORA, and GPR31) exhibited high diagnostic efficacy. Four biomarkers (ADM, NUPR1, PTGER1, and PYDC2) were identified using Support Vector Machine (SVM). Ten types of immune cells, including CD8⁺ T cells, regulatory T cells (Tregs), and resting NK cells, showed significant differences between the CAD and normal groups. Furthermore, increased levels of ADM, NUPR1, PTGER1, and PYDC2 were validated in PBMCs isolated from CAD patients. In addition, ADM, NUPR1, and PTGER1 were upregulated in the mouse atherosclerotic aorta. Conclusion: Our findings revealed novel inflammatory gene signatures of CAD that could be potential biomarkers for the early diagnosis of CAD.