Micro-RNAs in abdominal aortic aneurysms: insights from animal models and relevance to human disease

Abstract

Abdominal aortic aneurysm (AAA) is a major health concern and may be associated with high rates of mortality linked to acute complications. Diagnosis and treatment are, respectively, based on imaging and surgical techniques. Drug-based therapies are still mostly ineffective, which highlight a real unmet need. Major pathophysiological mechanisms leading to aneurysm formation involve inflammatory processes, degradation of the extracellular matrix, and loss of smooth muscle cells. However, the precise cellular and molecular pathways are still poorly understood. Recently, microRNAs have emerged as major intracellular players in a wide range of biological processes, and their stability in extracellular medium within microvesicles has led to propose them as mediators of intercellular crosstalk and as potential biomarkers and therapeutic targets in a variety of disease settings. To date, several studies have been performed to address the involvement of micro-RNAs (miRs) in aneurysm formation and complications. Here, we discuss the roles and implications of miRs in animal models and their relevance to human AAA.

MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin

“…A , miR-181b inhibition did not alter blood pressure levels. B , Quantification of aneurysm incidence and ( C ) severity (increasing severity from stage I to stage IV as described by Raffort et al 12 ) in both groups of mice, using Fisher exact test and 2-tailed Student t test, respectively, n=6 to 8/group, * P <0.05. D , Quantification of miR-181b expression by quantitative polymerase chain reaction (Q-PCR) and ( E ) tissue inhibitor of metalloproteinase (TIMP)-3 protein expression by immunohistochemistry, n=6 to 8/group, ** P <0.01 compared with scrambled control mice, 2-tailed Student t test.…”

“…I , Quantification of elastin breaks in elastin van Gieson–stained ascending TAs, n=6 to 8/group, ** P <0.01 compared with scrambled control mice, 2-tailed Student t test, scale bar in i represents 25 μm and is applicable to both panels, arrows indicate areas of elastin fragmentation. J , Quantification and associated representative images of aneurysm severity (increasing severity from stage I to stage IV as described by Raffort et al 12 ) in scrambled control and miR-181b inhibitor-treated Ldlr −/− mice, using Fisher exact test, n=6 to 8/group, * P <0.05.…”

“…MiRs control several processes known to be involved with the initiation and progression of numerous cardiovascular diseases, such as atherosclerosis 11 and AAAs. 12 In particular, miR-181b is a highly conserved miR able to directly target TIMP-3 mRNA and repress TIMP-3 protein expression in hepatocarcinoma cells. 13 In addition, miR-181b is downregulated during macrophage colony-stimulating factor (M-CSF) maturation of macrophages, 10 whereas TIMP-3 protein and mRNA expression is enhanced.…”

MicroRNAs

“…Because of the nature of their binding, miRNAs can potentially bind multiple targets, and more and more evidence is linked to a strong regulatory effect of a single miRNA by binding several targets within the same functional network. Evidence is accumulating showing particularly important functional roles for miRNAs in cardiovascular disease, including atherosclerosis 5 and aneurysm formation, 6 which were recently extensively reviewed. miRNAs have been associated with cardiovascular disease risk factors, including hyperlipidemia, hypertension, obesity, diabetes mellitus, lack of physical activity, and smoking.…”

Targeting vascular remodeling in abdominal aortic aneurysm : To identify novel treatment strategies and drug candidates

“…The aorta is the largest and strongest artery in the body and consists of three distinct layers, Modified from (Raffort et al, 2016).…”