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Background: Vascular smooth muscle cell (VSMC) proliferation is of importance in the pathogenesis of vascular diseases such as restenosis or atherosclerosis. Endothelial microparticles (EMP) regulate function and phenotype of target endothelial cells (ECs), but their influence on VSMC biology is unknown. Hypothesis: Intercellular communication between ECs and VSMCs via EMPs regulates vascular remodelling. Methods and results: Systemic treatment of mice with EMPs after vascular injury reduced neointima formation in vivo. In vitro, EMP uptake in VSMCs diminished VSMC proliferation and migration, both pivotal steps in neointima formation. To explore the underlying mechanisms, Taqman microRNA-array was performed and microRNA (miR)-126-3p was identified as the predominantly expressed miR in EMP. Confocal microscopy revealed an EMP-mediated miR-126 transfer into recipient VSMCs. Expression of miR-126 target protein LRP6, regulating VSMC proliferation, was reduced in VSMCs after EMP treatment. Importantly, genetic regulation of miR-126 in EMPs showed a miR-126-dependent inhibition of LRP6 expression, VSMC proliferation and neointima formation in vitro and in vivo, suggesting a crucial role of miR-126 in EMP-mediated neointima formation reduction. Exposure of endothelial cells to pathological hyperglycaemic conditions prior to EMP release abrogated EMP-promoted neointima formation reduction. Finally, analysis of miR-126 expression in circulating MPs in 176 patients with coronary artery disease revealed a reduced PCI rate in patients with high miR-126 expression level, supporting a central role for MP-incorporated miR-126 in vascular remodelling. Conclusions: EMPs reduce VSMC proliferation, migration and subsequent neointima formation by delivering functional miR-126 into recipient VSMCs.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Deutsche Forschungsgemeinschaft Background  Coronary artery disease (CAD) is the leading cause of death worldwide. Lifestyle change is a crucial part of secondary prevention. Only 30% of CAD patients follow the corresponding guideline recommendations. The widespread adoption of smartphones offers the opportunity to integrate secondary prevention into the daily routine of CAD patients. Purpose  The purpose of this study was to show that smartphone-guided secondary prevention (SGSP) could achieve lifestyle changes and a gain of disease specific knowledge among CAD patients.  Methods  We developed an app to integrate secondary prevention into CAD patients’ everyday life. The app provided a daily 15-minute program that included video-guided exercises, video sessions with background information about CAD, and a tool to record blood pressure and heart rate once a day. The SGSP app was tested with the primary outcome of 28-day adherence. The secondary outcome was a composite of self-reported behavioural changes, gain of knowledge about cardiovascular risk factors and an increase in quality of life. Results  Of the 66 patients screened, 43 (65%) were included into the study and, of those, 17 (40%) used the app continuously for 28 days. From this group, 14 (82%) were physically more active and ten (59%) improved their dietary habits. Usage of the SGSP app was also associated with a gain of knowledge about cardiovascular risk factors (70% physical activity, 59% healthy diet). Conclusion  The regular use of a SGSP app appears to support lifestyle changes in patients with CAD. Primary and secondary endpoints Results Overall(n = 17) P-Value Adherence (28 days) 17 (39.5) 0.34 Behavioural change Significantly increased physical activity no. (%) 14 (82.4) 0.08 Implemented a healthier diet no. (%) 10 (58.8) 0.64 Relevant gain of knowledge about CVRF Physical activity no. (%) 12 (70.6) 0.13 Unhealthy diet no. (%) 10 (58.8) 1.00 Smoking no. (%) 1 (5.9) 0.47 Stress no. (%) 7 (41.2) 0.13 Potential for long-term use Willingness to use the App over a long time period (>28 days), no. (%) 15 (88.2) 1.00 Abstract Figure.

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