miRNAs: roles and clinical applications in vascular disease

Abstract

AbstractmiRNAs are small, endogenously expressed noncoding RNAs that regulate gene expression, mainly at the post-transcriptional level, via degradation or translational inhibition of their target mRNAs. Functionally, an individual miRNA can regulate the expression of multiple target genes. The study of miRNAs is rapidly growing and recent studies have revealed a significant role of miRNAs in vascular biology and disease. Many miRNAs are highly expressed in the vasculature, and their expression is dysregulated in diseased vessels. Several miRNAs have been found to be critical modulators of vascular pathologies, such as atherosclerosis, lipoprotein metabolism, inflammation, arterial remodeling, angiogenesis, smooth muscle cell regeneration, hypertension, apoptosis, neointimal hyperplasia and signal transduction pathways. Thus, miRNAs may serve as novel biomarkers and/or therapeutic targets for vascular disease. This article summarizes the current studies related to the disease correlations and functional roles of miRNAs in the vascular system and discusses the potential applications of miRNAs in vascular disease. Keywordsatherosclerosis; biomarker; lipoprotein metabolism; miRNA; therapeutic target; vascular disease; vascular smooth muscle cell The cardiovascular system is composed of the heart, blood vessels and blood. It is connected intimately with every other organ system, and dysfunction of the cardiovascular system can have devastating downstream effects. The lumen of blood vessels is lined by a monolayer of endothelial cells, which forms the main physical barrier between the blood and vessel wall, controlling the movement of solutes and fluid from the vascular space to the surrounding tissues [1]. Endothelial dysfunction owing to breakdown of the endothelial cell-cell barrier can promote atherogenesis through the increased adherence of leukocytes, monocytes and macrophages, and subendothelial accumulation of cholesterol-bearing lipoproteins [2,3]. Meanwhile, vascular smooth muscle cells (VSMCs) below the endothelium undergo phenotypic modulation from a contractile phenotype to a proliferative state under the influence of mechanical stress, growth factors, inflammatory mediators, such as low-density lipoprotein (LDL) deposition, and leukocyte or monocyte infiltration [4]. Aberrant

Porphyromonas gingivalis Induction of MicroRNA-203 Expression Controls Suppressor of Cytokine Signaling 3 in Gingival Epithelial Cells

“…miRNAs are abundant in the human genome and have emerged as a key component of pathway and network control in a wide range of important cellular processes, including inflammation and apoptosis (3,25,64). miRNAs also contribute to host responses to bacterial and viral infections (6,32,35).…”

MicroRNAs: Novel regulatory molecules in acute lung injury/acute respiratory distress syndrome

“…miRNAs are highly conserved, and are composed of ~22-nucleotide, single-stranded, small non-coding RNAs that can extensively regulate the expression of target genes at the post-transcriptional level (13)(14)(15)(16). Mature miRNA is formed via cleavage of the primary transcript (pri-miRNA) by the RNase III type endonucleases Drosha (also known as RN3) and Dicer, followed by incorporation into the RNA-induced silencing complex, which interacts with mRNA and regulates the expression of target gene (17)(18)(19)(20)(21).…”

“…Alterations in the expression of certain miRNAs participate in the regulation of the inflammatory process and tissue repair in ALI/ARDS, as these changes are concomitant to the increased levels of the inflammatory mediators, including the pro-inflammatory cytokines such as IL-1β, TNF-α, IL-6 and (16,30,31). Therefore, miRNAs have a considerable regulatory function in inflammation process and immune response in ALI.…”

ge dependent vascular remodeling in elderly patients with arterial hypertension

“…Taking into consideration deciphered mechanisms of vascular remodeling, linear age dependent increase of IMT seems to be hardly probable [10,11,12]. According to biomechanics, the normal artery is subjected to 3 primary mechanical stresses: a blood flow-induced wall shear stress, a blood pressure-induced circumferential wall stress, and an axial wall stress that appears to arise during development and to persist into maturity because of the long half-life of elastin.…”