EVs-miR-17-5p attenuates the osteogenic differentiation of vascular smooth muscle cells potentially via inhibition of TGF-ß signaling under high glucose conditions.

Vascular calcification, which is a major complication of diabetes mellitus, is an independent risk factor for cardiovascular disease. Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is one of the key mechanisms underlying vascular calcification. Emerging evidence suggests that macrophage-derived extracellular vesicles (EVs) may be involved in calcification within atherosclerotic plaques in patients with diabetes mellitus. However, the role of macrophage-derived EVs in the progression of vascular calcification is largely unknown. In this study, we investigated whether macrophage-derived EVs contribute to the osteogenic differentiation of VSMCs under high glucose conditions. We isolated EVs that were secreted by murine peritoneal macrophages under normal glucose (EVs-NG) or high glucose (EVs-HG) conditions. miRNA array analysis in EVs from murine macrophages showed that miR-17-5p was significantly increased in EVs-HG compared with EVs-NG. Prediction analysis with miRbase identified transforming growth factor ß receptor type II (TGF-ß RII) as a potential target of miR-17-5p. EVs-HG as well as miR-17-5p overexpression with lipid nanoparticles inhibited the gene expression of Runx2, and TGF-ß RII. Furthermore, we demonstrated that VSMCs transfected with miR-17-5p mimic inhibited calcium deposition. Our findings reveal a novel role of macrophage-derived EVs in the negative regulation of osteogenic differentiation in VSMCs under high glucose conditions.

Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on the Severity and the Mortality of Acute Myocardial Infarction in Japan　- Analysis From the JROAD-DPC Database.

Background: Coronavirus disease 2019 (COVID-19) has impacted on cardiovascular disease. However, it remains unclear whether the COVID-19 pandemic has impacted on disease severity and patients' prognosis of acute myocardial infarction (AMI) in Japan. Methods and Results: We retrospectively accumulated data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) study (April 2019 to March 2021). Patients were divided into a before COVID-19 pandemic group or a during COVID-19 pandemic group. The proportion of patients who presented with cardiogenic shock (Killip class IV) was compared between groups, in association with 30-day mortality as the primary outcome. Killip class IV AMI significantly increased in the during COVID-19 pandemic group (15.7% vs. 14.5% in the before pandemic group, P<0.0001). The 30-day mortality was higher in the during COVID-19 pandemic group (9.6% vs. 9.2% in the before COVID-19 pandemic group, P=0.049). However, there was no significant difference in the adjusted 30-day mortality in each Killip class between the before and during COVID-19 pandemic groups. Conclusions: During the early stage of the COVID-19 pandemic in Japan, 30-day mortality of AMI increased, mainly because of the increase of Killip class IV AMI patients. However, irrespective of the COVID-19 pandemic, the adjusted 30-day mortality of each Killip classification group was unchanged.

Fulminant necrotizing eosinophilic myocarditis after COVID-19 vaccination survived with mechanical circulatory support.

A 69-year-old man was hospitalized for heart failure 7 days after coronavirus disease 2019 (COVID-19) mRNA vaccination. Electrocardiography showed ST-segment elevation and echocardiography demonstrated severe left ventricular dysfunction. Venoarterial extracorporeal membrane oxygenation and Impella 5.0 were instituted because of cardiogenic shock and ventricular fibrillation. Endomyocardial biopsy demonstrated necrotizing eosinophilic myocarditis (NEM). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) PCR test was negative. He had no infection or history of new drug exposure. NEM was likely related to COVID-19 vaccination. He was administered 10 mg/kg of prednisolone following methylprednisolone pulse treatment (1000 mg/day for 3 days). Left ventricular function recovered and he was weaned from mechanical circulatory support (MCS). Follow-up endomyocardial biopsy showed no inflammatory cell infiltration. This is the first report of biopsy-proven NEM after COVID-19 vaccination survived with MCS and immunosuppression therapy. It is a rare condition but early, accurate diagnosis and early aggressive intervention can rescue patients.