Introduction & ObjectiveMicrovesicles (MVs) derived from mesenchymal stem cells (MSCs) have been shown to promote angiogenesis. This study was aimed to shed a light on the mechanisms by analyzing the angiogenesis-promoting compositions of MSC-MVs. Also we try to figure out the impact of hypoxia on angiogenesis.MethodsMVs were isolated from the culture supernatants of MSCs under hypoxia/normoxia and serum-deprivation condition. The morphological features of MVs were revealed by an electron microscope and the origin of the MVs was identified by a bead-bound assay. An antibody array was used to analyze the expression of angiogenic cytokines from MVs and the parent MSCs as well. The major candidate factors were screened and the results were validated by immune blotting.ResultsMSC-MVs were around 80 nm in diameter. They expressed CD29, CD44, and CD73, but not CD31 and CD45. Antibody array showed that both MSCs and MVs expressed many angiogenesis-promoting biomolecules, including interleukin-6 (IL-6), basic fibroblast growth factors (bFGF), and recptor of urokinase-type plasminogen activator (UPAR). MSC-MVs contained angiogenin, vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) and the receptor-2 for vascular endothelial growth factor at higher levels than the parent MSCs. Under hypoxic condition most cytokines were expressed in greater quantity than normoxic in MSCs while in MVs there was no significant difference between hypoxic and normoxic conditions except UPAR, Angiogenin, VEGF, IGF, Tie-2/TEK, and IL-6 which were higher in MVs under hypoxic conditions than those in normoxic condition.ConclusionUpon serum-deprivation condition, MSCs could secrete MVs that contain a variety of factors contributing to their angiogenesis-promoting function. And among them, Angiogenin, VEGF, MCP-1, VEGF R2 might be of greater importance than the other cytokines. Also UPAR, Angiogenin, VEGF, IGF, Tie-2/TEK, IL-6 might be responsible for hypoxia-augmented proangiogenic effects of MVs.

Aim: Microvesicles (MVs) are nanoscale membrane fragments released from virtually all cell types upon activation or apoptosis, and may contribute to the beneficial effects of stem cell therapy. In this study, we investigated the therapeutic effects of mesenchymal stem cell (MSC) derived MVs (MSC-MVs) on pulmonary artery hypertension (PAH) in rats. Methods: MSC-MVs were isolated from rat bone marrow MSCs that were cultured in a serum-free conditioned medium. Transmission electron microscopy (TEM), flow cytometry and nanoparticle tracking analysis (NTA) were used to characterize the MVs. Adult SD rats were injected with monocrotaline (50 mg/kg, sc) to induce PAH. Three weeks later, the rats were intravenously injected with MSCs, MSC-MVs or saline for 2 weeks. At the end of treatments, the hemodynamic parameters and pathological right ventricular and pulmonary arterial remodeling were analyzed in each group. Results: The MSC-MVs showed general morphologic characteristics of MVs and expressed annexin V and CD29 markers under TEM, and their size ranged from 40 to 300 nm. Intravenous injection of MSC-MVs or MSCs significantly ameliorated the mean pulmonary artery pressure (mPAP) and mean right ventricle pressure (mRVP) in PAH rats. Furthermore, intravenous injection of MSC-MVs or MSCs significantly decreased the right ventricle (RV) hypertrophy and pulmonary arteriole area index (AI) and thickness index (TI) in PAH rats. Conclusion: Intravenous injection of MSC-MVs or MSCs produces similar beneficial effects for treating PAH, and our results provide a basis for cell-free approach in stem cell therapy.

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The association of adiposity indices with prehypertension remains unclear in the Chinese non‐hypertensive population. This study aimed to compare the association of adiposity indices, including waist circumference (WC), waist‐to‐height ratio, body roundness index (BRI), a body shape index (ABSI), and conicity index (CI), and prehypertension in the Chinese population. We recruited 61 475 participants from a population‐based screening project in Guangdong province, China. Multiple logistic regression analyses were performed to detect the association between the six adiposity indices and prehypertension. Receiver operator characteristic curve (ROC) analysis was used to evaluate the predictive values of adiposity indices to prehypertension. The individuals were divided into two categories by blood pressure (BP) levels: normotension (<120/80 mmHg) and prehypertension (120–139/80–89 mmHg). A total of 33 233 people had prehypertension, with a prevalence of 54.04% and 42% males. Both logistics regression models presented a positive association between each adiposity index and prehypertension (p < .05), except for ABSI. The body mass index (BMI) was slightly more correlated with prehypertension than any other index. The standardized ORs for the six indices were 1.392, 1.361, 1.406, 1.039, 1.372, and 1.151, respectively. Compared to other adiposity indices, the WC had a significantly higher area under the curve (AUC) for predicting prehypertension (AUC: .619, sensitivity: 57%, specificity: 60.6%). In conclusion, WC and BMI might be the best indicators for prehypertension. Increasing evidence supports avoiding obesity as a preferred primary prevention strategy for prehypertension while controlling other major hypertension risk factors.