Abstract
AimsAccumulating evidence suggest that numerous microRNAs (miRNAs) play important roles in cell proliferation, apoptosis, and differentiation, as well as various diseases that accompany inflammatory responses. Inflammation is known to be a major contributor to atherogenesis. Previous studies provide promising evidence in support of the role of miRNAs in cardiovascular disease. However, mechanistic data on these small molecules in atherosclerosis (AS) are still missing. The present study aims to investigate the potential role of miRNAs in AS.Methods and ResultsThe miRNA transcriptase was verified by TaqMan real-time polymerase chain reaction assay. Thoracic aorta samples were obtained from Apolipoprotein E knockout mice, and plasma samples were from coronary artery disease (CAD) patients. The results showed that the miR-155 level was the most significantly elevated both in AS mice and CAD patients relative to the normal control. The functional role of miR-155 in the atherosclerotic path physiological process was also observed in vivo and in vitro. The observations suggested that miR-155 is a part of a negative feedback loop, which down-modulates inflammatory cytokine production and decreases AS progression. miR-155 was also found to mediate the inflammatory response and mitogen-activated protein kinase (MAPK) pathway by targeting mitogen-activated protein kinase kinase kinase 10.ConclusionsmiR-155 contributes to the prevention of AS development and progression. It may also be involved in the posttranscriptional regulation of the inflammatory response and MAPK pathway by targeting mitogen-activated protein kinase kinase kinase 10.
Highlights
Atherosclerosis (AS) is a multifactorial disease driven, in part, by chronic inflammation in response to cholesterol accumulation
Thoracic aorta samples were obtained from Apolipoprotein E knockout mice, and plasma samples were from coronary artery disease (CAD) patients
The results showed that the miR-155 level was the most significantly elevated both in AS mice and CAD patients relative to the normal control
Summary
Atherosclerosis (AS) is a multifactorial disease driven, in part, by chronic inflammation in response to cholesterol accumulation. Inflammation is recognized as a major contributor to atherogenesis [1] These effects are mediated by the components of the innate immune system (macrophages and dendritic cells, DCs) and of the adaptive immune system (T lymphocytes) [2]. Little is known regarding the complex upstream regulators of gene expression and translation involved in the responses to AS. MiR-155 is highly expressed in activated B cells, T cells, macrophages, and DCs [8]. It is up-regulated in primary murine macrophage and oxidized low density lipoprotein (oxLDL)-stimulated monocytes [9,10]. All miRNA-dependent regulators of immune cells are involved in the control of vascular inflammation
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