7 research outputs found

    Canagliflozin Increases Postprandial Total Glucagon-Like Peptide-1 Levels in the Absence of α-Glucosidase Inhibitor Therapy in Patients with Type 2 Diabetes: A Single-Arm, Non-Randomized, Open-Label Study.

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    Defective autophagy in vascular smooth muscle cells enhances cell death and atherosclerosis

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    <p>Macroautophagy/autophagy is considered as an evolutionarily conserved cellular catabolic process. In this study, we aimed to elucidate the role of autophagy in vascular smooth muscle cells (SMCs) on atherosclerosis. SMCs cultured from mice with SMC-specific deletion of the essential autophagy gene <i>atg7</i> (<i>Atg7cKO</i>) showed reduced serum-induced cell growth, increased cell death, and decreased cell proliferation rate. Furthermore, 7-ketocholestrerol enhanced apoptosis and the expression of CCL2 (chemokine [C-C motif] ligand 2) with the activation of TRP53, the mouse ortholog of human and rat TP53, in SMCs from <i>Atg7cKO</i> mice. In addition, <i>Atg7cKO</i> mice crossed with <i>Apoe</i> (apolipoprotein E)-deficient mice (<i>apoeKO; Atg7cKO:apoeKO</i>) showed reduced medial cellularity and increased TUNEL-positive cells in the descending aorta at 10 weeks of age. Intriguingly, <i>Atg7cKO: apoeKO</i> mice fed a Western diet containing 1.25% cholesterol for 14 weeks showed a reduced survival rate. Autopsy of the mice demonstrated the presence of aortic rupture. Analysis of the descending aorta in <i>Atg7cKO:apoeKO</i> mice showed increased plaque area, increased TUNEL-positive area, decreased SMC-positive area, accumulation of macrophages in the media, and adventitia and perivascular tissue, increased CCL2 expression in SMCs in the vascular wall, medial disruption, and aneurysm formation. In conclusion, our data suggest that defective autophagy in SMCs enhances atherosclerotic changes with outward arterial remodeling.</p
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