Abstract
The arterial aneurysm refers to localized dilation of blood vessel wall and is common in general population. The majority of aneurysm cases remains asymptomatic until a sudden rupture which is usually fatal and of extremely high mortality (~ 50–60%). Therefore, early diagnosis, prevention and management of aneurysm are in urgent need. Unfortunately, current understanding of disease driver genes of various aneurysm subtypes is still limited, and without appropriate biomarkers and drug targets no specialized drug has been developed for aneurysm treatment. In this research, aneurysm subtypes were analyzed based on protein–protein interaction network to better understand aneurysm pathogenesis. By measuring network-based proximity of aneurysm subtypes, we identified a relevant closest relationship between aortic aneurysm and aortic dissection. An improved random walk method was performed to prioritize candidate driver genes of each aneurysm subtype. Thereafter, transcriptomes of 6 human aneurysm subtypes were collected and differential expression genes were identified to further filter potential driver genes. Functional enrichment of above driver genes indicated a general role of ubiquitination and programmed cell death in aneurysm pathogenesis. Especially, we further observed participation of BCL-2-mediated apoptosis pathway and caspase-1 related pyroptosis in the development of cerebral aneurysm and aneurysmal subarachnoid hemorrhage in corresponding transcriptomes.
Highlights
Arterial aneurysm describes a class of vascular diseases with focal dilation of arteries, that affects all arterial layers [1]
We found that research progresses on various human aneurysm subtypes were not in sync, mainly focusing on certain popular subtypes like abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA) [7]
Through literature searches we found that the participant of ubiquitination related proteins (e.g. UCHL1, RNF213, UBR3, ARIH1) in pathogenesis of above-mentioned human aneurysm subtypes (ASH, AAA, cerebral aneurysm (CA), aortic aneurysm (AA), aortic dissection (AD)) has been widely reported before [15,16,17,18,19,20,21]
Summary
Arterial aneurysm describes a class of vascular diseases with focal dilation of arteries, that affects all arterial layers [1]. It might occur in various sites along the full length of arterial and present diverged morphologies, including saccular, fusiform, dissecting aneurysm and false aneurysm, sporadically or simultaneously. Improved random walk method is applied to investigate potential driver genes of various subtypes On this basis, we further study promising mechanisms contributing to aneurysm pathogenesis. We further study promising mechanisms contributing to aneurysm pathogenesis These findings could facilitate understanding similarities and differences between different aneurysm subtypes, and accelerate the development of novel therapy for aneurysmal diseases
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