Sodium-glucose cotransporter 1 promotes the biofunctions of perivascular preadipocytes mediated by Akt/mTOR/p70S6K signaling pathway.

The influence of SGLT-1 on perivascular preadipocytes (PVPACs) and vascular remodeling is not well understood. This study aimed to elucidate the role and mechanism of SGLT-1-mediated PVPACs bioactivity. PVPACs were cultured in vitro and applied ex vivo to the carotid arteries of mice using a lentivirus-based thermosensitive in situ gel (TISG). The groups were treated with Lv-SGLT1 (lentiviral vector, overexpression), Lv-siSGLT1 (RNA interference, knockdown), or specific signaling pathway inhibitors. Assays were conducted to assess changes in cell proliferation, apoptosis, glucose uptake, adipogenic differentiation, and vascular remodeling in the PVPACs. Protein expression was analyzed by Western blotting, immunocytochemistry, and/or immunohistochemistry. The methyl thiazolyl tetrazolium (MTT) assay and Hoechst 33342 staining indicated that SGLT-1 overexpression significantly promoted PVPACs proliferation and inhibited apoptosis in vitro. Conversely, SGLT-1 knockdown exerted the opposite effect. Oil Red O staining revealed that SGLT-1 overexpression facilitated adipogenic differentiation, while its inhibition mitigated these effects. 3H-labeled glucose uptake experiments demonstrated that SGLT-1 overexpression enhanced glucose uptake by PVPACs, whereas RNA interference-mediated SGLT-1 inhibition had no significant effect on glucose uptake. Moreover, RT-qPCR, Western blotting, and immunofluorescence analyses revealed that SGLT-1 overexpression upregulated FABP4 and VEGF-A levels and activated the Akt/mTOR/p70S6K signaling pathway, whereas SGLT-1 knockdown produced the opposite effects. In vivo studies corroborated these findings and indicated that SGLT-1 overexpression facilitated carotid artery remodeling. Our study demonstrates that SGLT-1 activation of the Akt/mTOR/p70S6K signaling pathway promotes PVPACs proliferation, adipogenesis, glucose uptake, glucolipid metabolism, and vascular remodeling.NEW & NOTEWORTHY SGLT-1 is expressed in PVPACs and can affect preadipocyte glucolipid metabolism and vascular remodeling. SGLT-1 promotes the biofunctions of PVPACs mediated by Akt/mTOR/p70S6K signaling pathway. Compared with caudal vein or intraperitoneal injection, the external application of lentivirus-based thermal gel around the carotid artery is an innovative attempt at vascular remodeling model, it may effectively avoid the transfection of lentiviral vector into the whole body of mice and the adverse effect on experimental results.

Exosomal circSCMH1/miR-874 ratio in serum to predict carotid and coronary plaque stability.

Background: To investigate the correlation between lg (circSCMH1/miR-874) and acute coronary syndrome (ACS), acute myocardial infarction (AMI), and carotid plaque stability. Methods: 701 patients were divided into stable coronary artery disease (SCAD), ACS, and control groups. Furthermore, 225 patients who underwent carotid ultrasound were selected from the above 701 patients and were divided into low-risk plaque, medium-to-high risk plaque, and control (without carotid plaques) groups. We collected their baseline characteristics and measured the contents of exosomal circSCMH1 and miR-874 in peripheral blood. Then lg(circSCMH1/miR-874) was calculated and statistical analysis was performed. Results: The lg (circSCMH1/miR-874) values of ACS, SCAD, and the control group decreased successively (P < 0.05). Compared with the low-risk plaque and control groups, the lg (circSCMH1/miR-874) value of medium-high risk plaque group decreased (P < 0.05). Multivariate logistic regression analysis showed that with the decrease of lg (circSCMH1/miR-874), the risk of ACS, AMI, and medium-high risk plaques increased. ROC curve analysis demonstrated that lg (circSCMH1/miR-874) has a higher diagnostic value for ACS, AMI and medium-high risk plaques than previously used predictive ratios. Conclusion: Lg (circSCMH1/miR-874) is closely associated with coronary and carotid plaque stability.

Correlation of neck circumference, coronary calcification severity and cardiovascular events in Chinese elderly patients with acute coronary syndromes.

BACKGROUND AND AIMS: We aimed to investigate whether neck circumference (NC) can predict metabolic syndrome (MetS), coronary calcification and lesion, and major adverse cardiovascular events (MACEs). METHODS: A total of 867 patients with acute coronary syndrome (ACS) over 60 years old from the Second Hospital of Shandong University, who had undergone coronary computed tomography, were randomly selected for a retrospective analysis. The subjects were divided into male and female groups, NC quartile 1-4 groups (Q1-Q4 groups), non-multivessel coronary disease (non-MVCD) and multi-vessel coronary disease (MVCD) groups. RESULTS: After adjusting for potential confounders, NC was associated with risk factors promoting coronary artery disease (CAD) and coronary artery calcification score (CACS). The severity of CAD increased by 0.202 times and 0.372 times for each unit of NC in male and female groups, respectively. Compared with the lower CACS group, the risk of coronary calcification increased by 0.139 times, and MVCD increased 0.268 times, with each unit increase of NC. Except for all-cause death, there were significant differences between the Q1-Q4 groups in the prevalence of all primary endpoints, cardiogenic death, unexpected re-hospitalization of heart failure, ACS recurrence or unplanned revascularization, and non-fatal stroke (p log-rank <0.01). In view of the overall trend, with the increase of NC quartiles, the prevalence of MACEs gradually increased (all p < 0.01). CONCLUSIONS: NC is closely associated with MetS and its components, coronary calcification and lesion degree, and MACEs. NC could be used as surrogate of CACS to predict the coronary condition and prognosis of elderly patients with ACS.