MicroRNA-155 Regulates ROS Production, NO Generation, Apoptosis and Multiple Functions of Human Brain Microvessel Endothelial Cells Under Physiological and Pathological Conditions.

The microRNA-155 (miR155) regulates various functions of cells. Dysfunction or injury of endothelial cells (ECs) plays an important role in the pathogenesis of various vascular diseases. In this study, we investigated the role and potential mechanisms of miR155 in human brain microvessel endothelial cells (HBMECs) under physiological and pathological conditions. We detected the effects of miR155 silencing on ROS production, NO generation, apoptosis and functions of HBMECs at basal and in response to oxidized low density lipoprotein (ox-LDL). Western blot and q-PCR were used for analyzing the gene expression of epidermal growth factor receptor (EGFR)/extracellular regulated protein kinases (ERK)/p38 mitogen-activated protein kinase (p38 MAPK), phosphatidylinositol-3-kinase (PI3K) and serine/threonine kinase(Akt), activated caspase-3, and intercellular adhesion molecule-1 (ICAM-1). Results showed that under both basal and challenge situations: (1) Silencing of miR155 decreased apoptosis and reactive oxygen species (ROS) production of HBMECs, whereas, promoted nitric oxide (NO) generation. (2) Silencing of miR155 increased the proliferation, migration, and tube formation ability of HBMECs, while decreased cell adhesion ability. (3) Gene expression analyses showed that EGFR/ERK/p38 MAPK and PI3K/Akt were increased and that activated caspase-3 and ICAM-1 mRNA were decreased after knockdown of miR155. In conclusion, knockdown of miR155 could modulate ROS production, NO generation, apoptosis and function of HBMECs via regulating diverse gene expression, such as caspase-3, ICAM-1 and EGFR/ERK/p38 MAPK and PI3K/Akt pathways.

Cellular Membrane Microparticles: Potential Targets of Combinational Therapy for Vascular Disease.

Vascular disease constitutes the leading health problem throughout the entire world. Current therapies for vascular disease mainly rely on comprehensive strategies including control of risk factors, vascular interventions and conventional supportive treatments. To improve the preventive and therapeutic efficacies of current approaches, novel combinational therapies are required. Microparticles (MPs) are small membrane vesicles derived from cells undergoing stress, activation or apoptosis. They carry the characteristics of their parent cells, enabling them to serve as potential biomarkers for various diseases. Of note, MPs also have been shown to mediate cell communications through transferring membrane proteins, phospholipids and RNAs from their parent cells to recipient cells. Recent novel approaches have started to reveal the functions of MPs. In this review, we summarize the general concepts and the latest research progress in MPs. And the potential of MPs as novel targets of combinational therapy for vascular disease will be discussed.