Extracellular Vesicles From Women With Severe Preeclampsia Impair Vascular Endothelial Function.

BACKGROUND: Preeclampsia (PE) manifesting as hypertension and organ injury is mediated by vascular dysfunction. In biological fluids, extracellular vesicles (EVs) containing microRNA (miRNA), protein, and other cargo released from the placenta may serve as carriers to propagate injury, altering the functional phenotype of endothelial cells. PE has been consistently correlated with increased levels of placenta-derived EVs (pEVs) in maternal circulation. However, whether pEVs impaired endothelial cell function remains to be determined. In this study, we hypothesize that pEVs from pregnant women with severe PE (sPE) impair endothelial function through altered cell signaling. METHODS: We obtained plasma samples from women with sPE (n = 14) and normotensive pregnant women (n = 15) for the isolation of EVs. The total number of EV and pEV contribution was determined by quantifying immunoreactive EV-cluster of designation 63 (CD63) and placental alkaline phosphatase (PLAP) as placenta-specific markers, respectively. Vascular endothelial functional assays were determined by cell migration, electric cell-substrate impedance sensing in human aortic endothelial cells (HAECs), and wire myography in isolated blood vessels, preincubated with EVs from normotensive and sPE women. RESULTS: Plasma EV and pEV levels were increased in sPE when compared to normotensive without a significant size distribution difference in sPE (108.8 ± 30.2 nm) and normotensive-EVs (101.3 ± 20.3 nm). Impaired endothelial repair and proliferation, reduced endothelial barrier function, reduced endothelial-dependent vasorelaxation, and decreased nitrite level indicate that sPE-EVs induced vascular endothelial dysfunction. Moreover, sPE-EVs significantly downregulated endothelial nitric oxide synthase (eNOS and p-eNOS) when compared to normotensive-EV. CONCLUSIONS: EVs from sPE women impair endothelial-dependent vascular functions in vitro.

Role of exosomal microRNA signatures: An emerging factor in preeclampsia-mediated cardiovascular disease.

Preeclampsia (PE) and vascular dysfunction are major causes of maternal and neonatal morbidity and mortality. Although extensively studied, the complete understanding of the pathophysiology behind PE remains unclear. Current reports indicate that exosomes are essential mediators in PE-related cardiovascular disease (CVDs). Exosomes are synthesized from multivesicular bodies (MVB) and contain functionally active microRNAs miRNAs). These miRNAs have been shown to mediate physiological and pathological functions through autocrine, paracrine, and endocrine signaling mechanisms. The role of miRNAs in pregnant women with PE has been studied extensively. However, little is known about the effect of exosomal miRNAs (exomiR) in PE. This paper will review and discuss the existing evidence for exomiR function in PE and highlight the need for future studies to explore the role that exomiR signatures have in cardiovascular dysfunction associated with PE.

Protective role of wild garlic on isoproterenol-induced myocardial necrosis in wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tulbaghia violacea Harv. (TVL) is a folk medicine, native to South Africa which has previously shown antioxidant, anti-hypertensive and anti-diabetic effects. THE AIM OF THE STUDY: The aim of the current study was to investigate the protective role of wild garlic or TVL on isoproterenol (ISO)-induced myocardial necrosis in rats. MATERIALS AND METHODS: Animal (n = 6 each group) were pre and co-treated with TVL (60 mg/kg body weight) daily for 30 days. Myocardial necrosis was administrated by subcutaneous injection of ISO (85 mg/kg body weight) into rats on 29th and 30th day. On the 31st day, rats were anaesthetized and blood, heart samples were obtained for the biochemical, histopathological and molecular study. The specific protein target analysis from TVL was done by reverse docking study (reverse pharmacophore mapping) using PharmMapper. RESULTS: The levels of cardiac markers, lipid peroxidation products, and heart rate were considerably increased in ISO-induced myocardial necrosis in rats whilst plasma enzymatic antioxidants were significantly decreased. Myocardial necrotic mRNA genes were increased in ISO-induced myocardial necrosis in rats compared to controls. Pre and co-treatment with TVL and ramipril of myocardial necrosis in rats showed significant effects on all the biochemical and molecular studies evaluated. TVL reduced heart rate, prevented oxidative stress and downregulated the Fas-receptor and caspase-mediated apoptosis-signaling pathway, and heart muscle damage in myocardial necrosis in rats. The specific target protein [disulfide, bis (2-sulfhydrylethyl] from TVL mediates the protective effects. CONCLUSION: Wild garlic or TVL extract has shown a protective effect on ISO-induced myocardial necrosis in rats by increasing antioxidant production confirmed with docking studies.