Exosomes (Exo) secreted from hypoxia-conditioned bone marrow mesenchymal stem cells (BM-MSCs) were found to be protective for ischemic disease. However, the role of exosomal miRNA in the protective effect of hypoxia-conditioned BM-MSCs-derived Exo (Hypo-Exo) remains largely uncharacterized and the poor specificity of tissue targeting of Exo limits their clinical applications. Therefore, the objective of this study was to examine the effect of miRNA in Hypo-Exo on the repair of ischemic myocardium and its underlying mechanisms. We further developed modified Hypo-Exo with high specificity to the myocardium and evaluate its therapeutic effects.

Cardiometabolic multimorbidity (co-existence of ≥1 cardiometabolic diseases) is increasingly common, while its prevalence in the U.S. is unknown. We utilized data from 10 National Health and Nutrition Examination Survey (NHANES) two-year cycles in U.S. adults from 1999 to 2018. We reported the age-standardized prevalence of cardiometabolic multimorbidity in 2017–2018 and analyzed their trends during 1999–2018 with joinpoint regression models. Stratified analyses were performed according to gender, age, and race/ethnicity. In 2017–2018, the prevalence of cardiometabolic multimorbidity was 14.4% in the U.S., and it was higher among male, older, and non-Hispanic Black people. The three most common patterns were hypertension and diabetes (7.5%); hypertension, diabetes, and CHD (2.2%); and hypertension and CHD (1.8%). During 1999–2018, the prevalence of cardiometabolic multimorbidity in U.S. adults increased significantly, with an averaged two-year cycle percentage change (AAPC) of 3.6 (95% CI: 2.1 to 5.3). The increasing trend was significant for both genders, most age groups except for 60–79 years, and non-Hispanic White people. For common patterns, the trend was increasing for hypertension and diabetes and hypertension, diabetes, and CHD, while it was decreasing for hypertension and CHD. Our findings provide evidence that cardiometabolic multimorbidity has risen as an austere issue of public health in the U.S.

Regulating HSC progenitors via cholesterol: Atherosclerosis is characterized by the buildup of cholesterol-containing lipoproteins in the vascular wall. This increased cholesterol augments hematopoietic stem and progenitor cell (HSPC) counts, and the resultant increase in leukocytes is associated with increased cardiovascular disease. Gu et al. describe a mechanism orchestrating HSPC specification from the hemogenic endothelium (HE) during embryogenesis (see the Perspective by Rajan and Berman). ApoA-I binding protein accelerated cholesterol efflux from the HE, activating the transcription factor Srebp2, which in turn transactivated Notch signaling. This mechanism also appears to be important for adult HSPC expansion in hypercholesterolemia. Science , this issue p. 1085 ; see also p. 1041

Background: Although the association between shift work and individual cardiometabolic diseases has been well studied, its role in the progression to cardiometabolic multimorbidity (CMM) remains unclear. In this study, we investigate the association between shift work and the incidence of CMM in patients with hypertension. Methods and Results: This study is a population‐based and prospective cohort study on 36 939 UK Biobank participants. We used competing risk models to examine the association between shift work and the risk of CMM, which was defined as coexistence of hypertension and diabetes, coronary heart disease, or stroke in our study. We also investigated the association between the frequency and duration of shift work and CMM risks. In addition, we conducted a cross‐classification analysis with the combination of frequency and duration of shift work, chronotype and sleep duration as the exposure metrics. During a median follow‐up of 11.6 years, a total of 5935 participants developed CMM. We found that usually/always night shift workers were associated with a 16% higher risk of CMM compared with day workers (hazard ratio [HR], 1.16 [95% CI, 1.02–1.31]). We also found that a higher frequency of night shifts (>10/month) was associated with increased risk of CMM (HR, 1.19 [95% CI, 1.06–1.34]) that was more pronounced for >10/month in combination with a morning chronotype or 8 hours of sleep duration (HR, 1.26 [95% CI, 1.02–1.56]; HR, 1.43 [95% CI, 1.19–1.72], respectively). Conclusions: We find that night shift work is associated with higher CMM risk in patients with hypertension.

Myocardial infarction (MI) is the leading cause of death worldwide and can lead to the loss of cardiac function and heart failure. Reactive oxygen species (ROS) play a key role in the pathological progression of MI. The levels and effects of ROS are significantly different in three unique pathological stages of MI, and most antioxidants cannot make corresponding adjustments to eliminate ROS, which leads to a great compromise to treat MI with antioxidants. Herein, an innovative self‐sustaining antioxidant strategy is developed to treat MI with self‐sustaining selenium‐embedded nanoparticles (SSSe NPs). SSSe NPs possess unique self‐sustaining antioxidant effects at different pathological stages of MI. This strategy of on‐demand ROS elimination during different pathological stages demonstrated excellent MI treatment efficacy and effectively reversed heart failure to normal heart function. The therapeutic mechanism of SSSe NPs is intensively investigated through a series of experiments and mainly involved five critical aspects of myocardial repair: protecting mitochondria, reducing cardiomyocyte apoptosis and ferroptosis, reducing inflammation and fibrosis, and promoting angiogenesis. This strategy not only provides a promising treatment option for MI but also offers inspiration for other ischemic diseases.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.