Multi-omics analysis reveals size-dependent toxicity and vascular endothelial cell injury induced by microplastic exposure in vivo and in vitro

Microplastics (MPs) pollution has gained increasing attention recently. Fewer studies have examined the effects of these small items on the vascular system. The aim of this work was to precisely...

Effects of Levistilide A on Hemorheology and Endothelial Cell Injury in Rats with Blood Stasis

Background. Vascular endothelial cell injury is not only the initiating factor of cardiovascular and cerebrovascular diseases but also the essence of blood stasis. Levistilide A (LA), a natural component isolated from the traditional Chinese herb, Ligusticum chuanxiong Hort, has traditional effects on improving blood circulation and removing stasis. In this study, the effects and potential mechanisms of LA in the rat model of blood stasis and the mechanism in endothelial cell injury have been explored. Materials and Methods. In this experiment, the effects of LA on the model of acute blood stasis in rats were explored. The blood samples were collected for the measurement of coagulation and hemorheological indices, and the carotid arteries were also excised from rats for hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). In addition, the improvement effects of LA on the H2O2-induced human umbilical vein endothelial cell (HUVEC) injury model were evaluated. And the cell viability detection was conducted by the CCK8 assay, and the pathway-related protein expressions were detected by western blotting. Results. In vivo, compared with the model group, the treatment of LA (10 mg/kg) could reduce the FIB (fibrinogen) content ( P < 0.01 ), increase the INR (international normalized ratio) and PT (prothrombin time) ( P < 0.01 ), and reduce the plasma viscosity ( P < 0.05 ) and whole blood viscosities of low, medium, and high shear rates in the blood of blood stasis model rats ( P < 0.01 ). In vitro, the cell viability in the LA-pretreated group was higher than that of the model group ( P < 0.05 ). The expression levels of PI3K, AKT, and eNOs in the LA-pretreated group were increased ( P < 0.01 ) as compared to the model group. Conclusion. These findings demonstrated that LA has the ability to improve blood hypercoagulation and blood viscosity, and enhance the viability of cells. It is more likely that it exerts a protective effect on the endothelial cell through the PI3K-AKT-eNOs pathway. These results indicate LA will be a potential candidate to cure blood stasis with endothelial cell injury.

Sonic Hedgehog Improved Endothelial Cell Dysfunction and Attenuated The Development of Atherosclerosis In Mice

Sonic hedgehog (Shh), an evolutionally-highly conserved morphological factor whose maturation, transportation and function were closely related to cholesterol. Shh played an important role in maintaining adult coronary vasculature homeostasis. It not only induced angiogenesis to improve myocardial infarction but also inhibited ox-LDL induced endothelial apoptosis. However, the role of Shh in endothelial cell injury have not been fully elucidated. Here, we shown Shh induced nitric oxide (NO) release and endothelial nitric oxide synthase (eNOS) synthesis, which improved endothelial cell dysfunction and inhibited atherosclerotic plaque. In vivo, Shh reduced the plaque lesion in high fat diet (HFD) induced ApoE-/- mice. In endothelial cell, Shh improved NO and eNOS mRNA expression and inhibited intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) mRNA expression. In contrast, knockdown of Shh inhibited eNOS and NO level and induced ICAM-1 and VCAM-1. In conclusion, we found that Shh has anti-inflammation and improved endothelial cell injury consequently attenuated the development of atherosclerosis.

The Role of MicroRNA-155 in Glomerular Endothelial Cell Injury of Diabetic Nephropathy

Objective: To investigate the role of microRNA-155-5p (miR-155-5p) on apoptosis and inflammatory response in human glomerular endothelial cells (HRGEC) cultured with high glucose.Methods: The primary human glomerular endothelial cells (HRGEC) were studied, QPCR, WB , IF were used to detect cell morphology, target gene ETS-1 (ETS-1), downstream factors VCAM-1 and MCP-1, and apoptosis of cells in each group after high glucose stimulation and transfection with miR-155 overexpression or inhibitor.Results:1.The expression of inflammatory factors and apoptosis of HRGEC cells increased under high glucose stimulation.2.The overexpression of miR-155 in HRGEC cells under high glucose stimulation decreased the expression of ETS-1, while the expression of ETS-1 increased when miR-155 was inhibited. These results suggest that miR-155 may be involved in endothelial cell injury by negatively regulating the expression of ETS-1.3.HRGEC cells were transfected with miR-155 mimic and ETS-1 siRNA with high glucose stimulation. The expression of ETS-1 was positively correlated with the expression of downstream factors VCAM-1 and MCP-1. These results suggest that ETS-1 can mediate endothelial cell inflammation by regulating VCAM-1 and MCP-1.

Long Non-Coding RNA, Small Nucleolar RNA Host Gene 5, Inhibits the Oxidized Low-Density Lipoprotein Induced Vascular Endothelial Cell Injury by Targeting miR-26a-5p

Atherosclerosis is the major cause of cardiovascular disease, and endothelial cell injury is the primary atherogenic factor. Long non-coding RNAs (lncRNAs) are increasingly implicated as critical regulators of disease progression. Still, the role of lncRNA in endothelial cell injury is largely unknown. This issue was explored in control, ox-LDL stimulated, ox-LDL stimulated+transfected negative control vector, and ox-LDL stimulated+SNHG5 overexpression vector EA. hy926 cells. Quantitative real-time PCR used to assess the expression of SNHG5 and miR-26a-5p. Flow cytometry was used to evaluate cell apoptosis. Activity or concentration of SOD, MDA, CAT, and reactive oxygen species (ROS) was measured to assess oxidative stress. Western blotting was used to examine protein-level expression of cleaved Caspase-3, cleaved Caspase-9, and cyt-c in cytoplasm and mitochondria. Potential binding sites between SNHG5 and miR-26a-5p were predicted using Starbase software, and dual-luciferase reporter assays were used to identify target relationships. SNHG5 expression in cells following ox-LDL treatment was downregulated in EA. hy926 cells. Ox-LDL treatment promotes apoptosis, and increased C-Caspase-3, C-Caspase-9, and cytoplasmic cyt-c protein levels. MDA concentration and ROS activity were increased, while the activity of SOD and CAT was decreased. Transfection with SNHG5 reversed the effects of ox-LDL on cell apoptosis and oxidative stress. SNHG5 targeted miR-26a-5p and regulated its expression. miR-26a-5p mimics reversed SNHG5 modulation of apoptosis and oxidative stress. lncRNA SNHG5 targets to miR-26a-5p to regulate vascular endothelial cell injury induced by ox-LDL.

Deciphering the role of the Pancreatic Secretome in Covid-19 associated Multi-Organ Dysfunctions

Emerging evidence indicates an intricate relationship between the SARS-CoV-2 infection and Multi-Organ Dysfunctions (MODs). Here, we have investigated the role of the Secretome of the SARS-CoV-2 infected pancreas and mechanistically linked it with the multi-organ dysfunction using the scRNA-seq analysis. We found that acinar-specific PRSS2, REG3A, REG1A, SPINK1, and ductal-specific SPP1, MMP7 genes are upregulated in alpha, beta, delta, and mesenchyme cells. Using extensive documented experimental evidence, we validated the association of upregulated pancreatic Secretome with coagulation cascade, complement activation, renin angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of upregulated Secretome on multi-organ systems such as Nervous, Cardiovascular, Immune, Digestive, and Urogenital systems. In addition, we report that the secretory proteins IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF are associated with diverse diseases. Thus, suggest the role of the pancreatic Secretome in SARS-CoV-2 associated MODs.