Comparative analysis of aneurysm subtypes associated genes based on protein–protein interaction network

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.

Frail Silk: Is the Hughes-Stovin Syndrome a Behçet Syndrome Subtype with Aneurysm-Involved Gene Variants?

“…The non-muscle myosin light chain kinase (nmMLCK) is a 210 kDa cytoskeletal protein ( Figure 3 ), central for the regulation of vascular integrity and permeability by regulating actin cytoskeleton rearrangements and contraction, vascular endothelial barrier, angiogenesis, EC apoptosis, and neutrophil transmigration and diapedesis [ 40 , 50 , 51 ].…”

“…Certain MYLK polymorphisms may be associated with severe respiratory inflammatory disorders, such as asthma, acute respiratory distress syndrome, etc. [ 50 ]. Also, MYLK -associated vascular involvement may result in multiple arterial dissections in phenotypes distinct for the homozigosity or heterozigosity of the MYLK variant [ 27 , 58 ].…”

“…The nmMLCK regulates endothelial and vascular permeability, promoting EC cytoskeleton rearrangements [ 52 , 61 ]. Regulatory mRNAs controlling nmMLCK expression are triggered in response to inflammatory stimuli [ 50 , 61 ]. TNFα increases MYLK transcription in lung EC [ 61 ], while the transcription factor NRF2 represses it [ 50 ].…”

“…Regulatory mRNAs controlling nmMLCK expression are triggered in response to inflammatory stimuli [ 50 , 61 ]. TNFα increases MYLK transcription in lung EC [ 61 ], while the transcription factor NRF2 represses it [ 50 ]. Epigenetic modification of cytoskeletal dynamics is also important in BS [ 62 ].…”

“…Nevertheless, VEGF inhibition may result in aneurysms or dissections [ 79 ]. The ubiquitin-proteasome system (UPS), involved in SMC inflammation and phenotypic switch, is important in the common pathogenesis of aneurysms [ 50 ] and BS [ 80 ]. MLCK also intervenes in UPS regulation [ 81 ].…”