Abstract
Abdominal aortic aneurysms (AAA) are a complex disease with an unclear pathomechanism. A positive family history is emphasized as a significant risk factor, and a nonspecific model of inheritance suggests participation of epigenetic regulation in the pathogenesis of this disease. Past studies have implicated microRNAs in the development of AAA; therefore in this project, we measured miR-191 levels in AAA patients and compared them with a control group. We found that miR-191 levels were significantly elevated in aneurysmal patients, although this did not correlate with the available clinical data. We then developed an in vitro model where, using cells with an endothelial phenotype, we determined the effect of miR-191 on the transcriptome using RNA sequencing. Subsequent pathway analysis established that some of the perturbations mediated by miR-191 can be explained by several processes which have long been observed and described in literature as accompanying the development of abdominal aortic aneurysms.
Highlights
Abdominal aortic aneurysm (AAA) is defined as local dilatation of the main artery, exceeding its normal diameter by 50% [1]
AAA presents as a focal lesion, some evidence suggests that it can be regarded as a systemic disease and that the entire vascular system is impaired in patients with AAA, specific molecular mechanisms remain unknown [3]
We began by observing that miR-191 levels were significantly elevated in patients with abdominal aortic aneurysms, and we demonstrated, using an in vitro model, the consequences of elevated levels of one particular microRNA molecule for the endothelial cell transcriptome
Summary
Abdominal aortic aneurysm (AAA) is defined as local dilatation of the main artery, exceeding its normal diameter by 50% [1]. The pathogenesis of the disease is still unclear, but some risk factors has been established. Pathological processes involved in the formation of AAA include upregulation of proteolytic pathways, apoptosis of structural cells, oxidative stress, inflammation, and loss of the arterial wall matrix [2]. A positive family history is a risk factor, even though its genetic background is not fully understood [4]. There is no consistent model of inheritance in AAA [5]. All this points to possible involvement of epigenetic factors in the pathogenesis of this disease
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