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.

Background: Hydrogen peroxide (H ₂ O ₂ ) is a critical molecular signal in the development of abdominal aortic aneurysm ( AAA ) formation. Vascular peroxidase 1 ( VPO 1) catalyzes the production of hypochlorous acid ( HOC l) from H ₂ O ₂ and significantly enhances oxidative stress. The switch from a contractile phenotype to a synthetic one in vascular smooth muscle cells ( VSMC s) is driven by reactive oxygen species and is recognized as an early and important event in AAA formation. This study aims to determine if VPO 1 plays a critical role in the development of AAA by regulating VSMC phenotypic switch. Methods and Results: VPO 1 is upregulated in human and elastase‐induced mouse aneurysmal tissues compared with healthy control tissues. Additionally, KLF 4, a nuclear transcriptional factor, is upregulated in aneurysmatic tissues along with a concomitant downregulation of differentiated smooth muscle cell markers and an increase of synthetic phenotypic markers, indicating VSMC phenotypic switch in these diseased tissues. In cultured VSMC s from rat abdominal aorta, H ₂ O ₂ treatment significantly increases VPO 1 expression and HOC l levels as well as VSMC phenotypic switch. In support of these findings, depletion of VPO 1 significantly attenuates the effects of H ₂ O ₂ and HOC l treatment. Furthermore, HOC l treatment promotes VSMC phenotypic switch and ERK 1/2 phosphorylation. Pretreatment with U0126 (a specific inhibitor of ERK 1/2) significantly attenuates HOC l‐induced VSMC phenotypic switch. Conclusions: Our results demonstrate that VPO 1 modulates VSMC phenotypic switch through the H ₂ O ₂ / VPO 1/ HOC l/ ERK 1/2 signaling pathway and plays a key role in the development of AAA . Our findings also implicate VPO 1 as a novel signaling node that mediates VSMC phenotypic switch and plays a key role in the development of AAA . Clinical Trial Registration: URL : www.chictr.org.cn . Unique identifier: Chi CTR 1800016922.

Background: Although the association between beverages and a single cardiometabolic disease has been well studied, their role in disease progression from the single cardiometabolic disease state to cardiometabolic multimorbidity (CMM) state remains unclear. This study examined the associations between three types of beverages: sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and pure fruit/vegetable juices, and the incidence of CMM in patients with a single cardiometabolic disease. Methods: Our analysis included 37,994 participants from the UK Biobank who completed at least one dietary questionnaire and were diagnosed with only one cardiometabolic disease at the time of recruitment. Competing risk models were used to examine the association between the three types of beverages and incidence of CMM. We conducted analysis both in patients with any single cardiometabolic disease and in patients with specific cardiometabolic disease. Results: During a median follow-up of 9.1 years (interquartile range [IQR] 9.0–9.8), a total of 6399 participants developed CMM. The consumption of SSBs and ASBs (>1 serving per day) was associated with a higher risk of CMM (SSBs: hazard ratio [HR] 1.19, 95% confidence interval [95% CI] 1.08–1.31; ASBs: HR 1.15, 95% CI 1.04–1.27). Intake of pure fruit/vegetable juices was inversely associated with the incidence of CMM (0–1 serving per day: HR 0.90, 95% CI 0.85–0.94; >1 serving per day: HR 0.90, 95% CI 0.81–0.99). However, the association of the high-level consumption of pure fruit/vegetable juices (>1 serving per day) was not statistically significant after correcting for multiple testing. In the analysis of patients with specific cardiometabolic diseases, positive associations were observed in patients with hypertension for SSBs consumption, while inverse associations persisted in patients with cardiovascular disease (coronary heart disease or stroke) and in hypertensive patients for pure fruit/vegetable juice consumption. Conclusions: Consuming >1 serving of SSBs and ASBs per day was associated with a higher risk of CMM in patients with a single cardiometabolic disease. In contrast, intake of pure fruit/vegetable juices was inversely associated with the risk of CMM. Our findings highlight the need to limit the use of SSBs and ASBs in patients with a single cardiometabolic disease.

Background and Aims: Earlier studies evaluated the association between systolic blood pressure variability (SBPV) measured during a single period and risk of health outcomes. This study expanded upon existing evidence by examining the association between changes in SBPV over time and clinical outcomes in primary care settings. Methods: Visit-to-visit SBPV was determined as standard deviation of ≥3 systolic blood pressure values measured at 5–10 (Period 1) and 0–5 (Period 2) years before enrolment in the UK Biobank. Cox proportional hazards models were used to evaluate associations of absolute changes in SBPV and SBPV change patterns between these two periods with risk of cardiovascular disease (CVD), coronary heart disease (CHD), stroke, atrial fibrillation and flutter (AF), heart failure (HF), chronic kidney disease (CKD), dementia, and overall mortality. Results: A total of 36 251 participants were included with a median follow-up time of 13.9 years. In the fully adjusted models, an increased SBPV from Period 1 to Period 2 was significantly associated with an increased risk of CVD, CHD, stroke, CKD, and overall mortality (all P for trend < .005), reflecting a 23%–33% increased risk comparing participants with an increase in SBPV above Tertile 3 with those below Tertile 1. An increase in SBPV from Period 1 to Period 2 appeared to be associated with an increased risk of AF, HF, and dementia; however, the associations did not reach statistical significance at P < .005. The restricted cubic spline analysis did not reveal non-linear associations, as all P-values for non-linearity were >.05. Regarding SBPV change patterns, compared with the participants with consistently low SBPV, participants with a consistently high SBPV during the two periods had an increased risk of CVD, CHD, stroke, AF, HF, CKD, and overall mortality, with a risk evaluation of 28%–46%. The observed associations remained largely unchanged across subgroup and sensitivity analyses. Conclusions: An increase in SBPV over time was associated with an elevated risk of CVD, CKD, and overall mortality. These findings provide compelling evidence to inform the importance for the management of SBPV in clinical practice.