Vascular calcification is a common phenomenon in older adults. Intermedin (IMD) is a cardiovascular bioactive peptide inhibiting vascular calcification. In this study, we aimed to investigate whether IMD1-53 attenuates aging-associated vascular calcification. Vascular calcification was induced by vitamin D3 plus nicotine (VDN) in young and old rats. The calcification in aortas was more severe in old rats treated with VDN than young control rats, and IMD expression was lower. Exogenous administration of IMD1-53 significantly inhibited the calcium deposition in aortas and the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) in VDNtreated old rats. Moreover, levels of aging-related p16, p21 and β-galactosidase were all greatly decreased by IMD1-53. These results were further confirmed in rat and human VSMCs in vitro. In addition, IMD-deficient mouse VSMCs showed senescence features coinciding with osteogenic transition as compared with wild-type mouse VSMCs. Mechanistically, IMD1-53 significantly increased the expression of the anti-aging factor sirtuin 1 (sirt1); the inhibitory effects of IMD1-53 on calcification and senescence were blocked by sirt1 knockdown. Furthermore, preincubation with inhibitors of PI3K, AMPK or PKA efficiently blunted the upregulatory effect of IMD1-53 on sirt1. Consequently, IMD1-53 could attenuate aging-associated vascular calcification by upregulating sirt1 via activating PI3K/Akt, AMPK and cAMP/PKA signaling.

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Background: Atherosclerosis (AS) is a major risk factor for cardiovascular disease. microRNAs play a key role in gene regulation in the formation and development of atherosclerotic plaques. Herein, the role and target gene of miR-185 in AS were explored. Materials and methods: Cell viability, migration and invasion were examined by cell counting kit-8 (CCK-8) and transwell assay. The relative luciferase activity was measured by luciferase reporter assay. The levels of miR-185, STIM1, vascular endothelial growth factor (VEGF) and matrix metalloprotein-9 (MMP-9) were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Results: The results revealed that ox-LDL decreased miR-185 expression, and enhanced STIM1 expression in MOVAS cells, as well promoted cell viability, migration and invasion. 3ʹ-UTR of STIM1 contained miR-185 binding site according to the Targetscan. miR-185 silencing or STIM1 overexpression promoted the viability, migration and invasion of ox-LDL-induced MOVAS cells. miR-185 overexpression or STIM1 silencing had the opposite effect. Besides, miR-185 silencing upregulated the levels of VEGF and MMP-9 in vitro, and increased the lesions of arterial wall tissues and STIM1 positive rate in vivo. However, STIM1 silencing reversed these effects. Conclusions: Sum up, STIM1 was a potential target gene of miR-185 in AS. Knockdown of miR-185 facilitated the progression of AS through enhancing cell proliferation, migration and invasion via targeting STIM1. The research provides a novel view of miR-185/STIM1 axis function in AS development, and this targeting method may prevent and treat AS.

Key Points Question What are clinical outcomes and procedural success rates associated with percutaneous left atrial appendage occlusion (LAAO) among East Asian individuals? Findings In this cohort study of 3096 consecutively enrolled participants in China, LAAO was associated with a high procedural success rate and a low 30-day adverse event rate. Intraprocedural variations with the type of anesthesia, modality of image guidance, or whether a combined ablation procedure was performed or not had no associations with procedural success or thrombotic and bleeding events at 30 days. Meaning These findings suggest that LAAO among patients in China had a high procedural success rate and low major adverse event rates regardless of procedural configurations.

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