Huina Zhang

Elevated blood pressure has previously been associated with increased levels of circulating extracellular vesicles (EVs). However, studies on the relevance of EV cargos to hypertension are limited. Secreted protein acidic and rich in cysteine (SPARC) is involved in many metabolic diseases and endothelial dysfunction pathological processes. This study aimed to explore the association of serum EV‐derived SPARC with hypertension incidence. We conducted a cross‐sectional study on 125 Chinese, including 76 hypertension patients and 49 normotensive patients. Serum EVs were prepared via ultracentrifugation. The concentrations of serum EV‐derived SPARC and serum SPARC were measured by Luminex Assay. The correlations between serum EV‐derived SPARC and clinical variables were analyzed. Multivariate logistic regression analysis determined the association of serum EV‐derived SPARC levels with hypertension. Interaction subgroup analysis was used to evaluate the interaction of the relevant baselines on the association between serum EV‐derived SPARC levels and hypertension. Our findings revealed that the levels of SPARC derived from serum EVs were markedly elevated in individuals with hypertension, averaging 20.60 ng/mL (p < 0.01), when contrasted with the levels observed in normotensive subjects, which were 14.25 ng/mL (p < 0.01) in average. Multivariate logistic regression analysis revealed that serum EV‐derived SPARC levels were positively associated with hypertension (odds ratio [OR] 1.095; 95% confidence interval [CI] = 1.031–1.163; p value, 0.003), after adjusting for confounding factors. Interaction subgroup analysis demonstrated that no significant interaction with hypertension was observed for any particular covariate. The present study reveals that the elevated levels of serum EV‐derived SPARC were independently associated with hypertension.

Background: Growth differentiation factor 15 (GDF15) is a stress-inducible factor involved in the inflammatory progression of many complications, including type 2 diabetes mellitus (T2DM). Growing evidence suggests that molecules in extracellular vesicles (EVs) are associated with diabetes or diabetes-related complications. However, the correlation between serum extracellular vesicle-derived growth differentiation factor15 (EV-GDF15) and T2DM is unknown. The aim of this cross-sectional study is to investigate whether serum EV-GDF15 is associated with T2DM incidence. Methods: 116 individuals, including 78 T2DM and 38 non-T2DM, were recruited as participants. The concentrations of serum EV-GDF15 and serum GDF15 were determined by Luminex assay. Serum EVs were obtained by ultracentrifugation. Multivariate stepwise regression analysis was used to determine the association between serum GDF15 levels and fasting plasma glucose (FPG) as well as glycated hemoglobin (HbA1c). The association of serum EV-GDF15 levels with T2DM was determined by multivariate logistic regression analysis. Results: Our data showed that the levels of serum EV-GDF15 and serum GDF15 were significantly increased in T2DM patients compared with non-T2DM subjects (EV-GDF15 levels, 13.68 (6.61–23.44) pg/mL vs. 5.56 (3.44–12.09) pg/mL, P < 0.001; and serum GDF15 levels, 1025.49 (677.87–1626.36) pg/mL vs. 675.46 (469.53–919.98) pg/mL, P < 0.001). There was a linear correlation between EV-GDF15 levels and fasting plasma glucose (FPG) and Hemoglobin A1C (HbA1c) levels (normalized β = 0.357, P < 0.001; normalized β = 0.409, P < 0.001, respectively). Elevated levels of EV-GDF15 were accompanied by an increase in the proportion of patients with T2DM (from 47.5 to 78.9%) and a progressive independent association with the incidence of T2DM (from OR = 3.06, 95% CI 1.02–9.19, P = 0.047 to OR = 3.75, 95% CI 1.14–12.26, P = 0.029). Notably, high levels of serum GDF15 plus high levels of serum EV-GDF15 were significantly associated with T2DM more than either alone. Conclusion: This study elucidated that increased levels of GDF15 in serum EVs were independently associated with T2DM.

Background: Serum extracellular vesicle (EV)-derived arginase 1 (ARG 1) plays a critical role in diabetes-associated endothelial dysfunction. This study was performed to determine the levels of serum EV-derived ARG 1 in T2DM and non-T2DM participants and to examine the association of serum EV-derived ARG 1 with T2DM incidence. Methods: We performed a cross-sectional study in 103 Chinese, including 73 T2DM patients and 30 non-T2DM. Serum EVs were prepared via ultracentrifugation. Serum EV-derived ARG 1 levels were measured by enzyme-linked immunosorbent assay. The correlations between serum EV-derived ARG 1 and clinical variables were analyzed. The association of serum EV-derived ARG 1 levels with T2DM was determined by multivariate logistic regression analysis. Interaction subgroup analysis was used to evaluate the interaction of the relevant baselines on the association between serum EV-derived ARG 1 levels and T2DM. Results: Serum EV-derived ARG 1 levels were significantly higher in T2DM patients compared with non-T2DM patients (p < 0.001). Correlation analysis revealed that serum EV-derived ARG 1 levels were positively associated with fasting plasma glucose (FPG) (r = 0.316, p = 0.001) and glycated hemoglobin (HbA1c) (r = 0.322, p = 0.001). Serum EV-derived ARG 1 levels were significantly associated with T2DM, especially in the subgroup of T2DM for more than 10 years (OR 1.651, 95% CI = 1.066–2.557; P value, 0.025), after adjusting for confounding factors. Conclusions: Elevated concentration of serum EV-derived ARG 1 is closely associated with T2DM.

Purpose The aim of this study was to evaluate the effects of berberine on nitroglycerin (NTG) tolerance and explore the underlying mechanism involved. Methods NTG tolerance was induced by pre-exposure of Sprague-Dawley rat aortas to NTG in vitro or by pretreating Sprague-Dawley rats with an NTG patch in vivo. The aortas were pre-treated with berberine or PKC inhibitors for different durations of time before induction of NTG tolerance. NTG-induced vasorelaxations was measured on wire myograph. Primary vascular smooth cells (VSMCs) were used to dissect the underlying mechanism of berberine-induced inhibition of NTG tolerance. Results NTG tolerance induced by either prior exposure of rat aortas to NTG in vitro or pretreatment with an NTG patch in vivo was reversed by co-treatment with berberine, as well as the inhibitors of protein kinase C (PKC) and protein kinase C alpha (PKCα). The mechanistic study revealed that PKCα participated in the development of NTG tolerance as NTG increased the activity of PKCα with enriched PKCα membrane localization and elevated phosphorylation of PKCα in VSMCs, which was reversed by berberine or PKCα inhibitors. Conclusion This study is probably the first demonstration that berberine reverses NTG tolerance through inhibiting PKCα activity in VSMCs and PKCα is an important contributor to the development of NTG tolerance. These new findings suggest that berberine could become a promising drug for prevention of NTG tolerance and that targeting PKCα in VSMCs is likely to be a potential therapeutic strategy for reversal of NTG tolerance in blood vessels.