Differential Expression Analyses on Human Aortic Tissue Reveal Novel Genes and Pathways Associated With Abdominal Aortic Aneurysm Onset and Progression

被引:0
作者
Temprano-Sagrera, Gerard [1 ]
Peypoch, Olga [1 ,2 ]
Soto, Begona [1 ,2 ]
Dilme, Jaume [1 ,2 ,3 ]
Juscafresa, Laura Calsina [4 ,5 ]
Davtian, David [6 ,7 ]
Estadella, Mireia de la Rosa [1 ]
Nieto, Lluis [4 ]
Brown, Andrew [6 ,7 ]
Escudero, Jose Roman [1 ,2 ]
Vinuela, Ana [8 ]
Camacho, Mercedes [1 ,3 ]
Sabater-Lleal, Maria [1 ,9 ,10 ]
机构
[1] Inst Recerca St Pau IR St PAU, Unit Genom Complex Dis, St Quinti 77-79, Barcelona 08041, Spain
[2] Hosp Santa Creu & Sant Pau, Serv Angiol & Cirurgia Vasc Endovasc, Barcelona, Spain
[3] Ctr Invest Biomed Red Enfermedades Cardiovasc CIBE, Madrid, Spain
[4] Hosp Mar, Dept Vasc & Endovasc Surg, Barcelona, Spain
[5] Univ Pompeu Fabra, Dept Med & Surg, Barcelona, Spain
[6] Univ Dundee, Ninewells Hosp, Populat Hlth & Genom, Dundee, Scotland
[7] Univ Dundee, Med Sch, Dundee, Scotland
[8] Univ Newcastle, Biosci Inst, Fac Med Sci, Newcastle Upon Tyne, England
[9] Karolinska Inst, Dept Med, Cardiovasc Med Unit, Stockholm, Sweden
[10] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
来源
JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2024年 / 13卷 / 24期
关键词
abdominal aortic aneurysm; allele-specific expression; alternative splicing; differential expression; transcriptomics; RNA-SEQ; MITOCHONDRIAL DYSFUNCTION; THROMBOSPONDIN-1; PATHOGENESIS; VALIDATION; MECHANISMS; DISEASE; COHORT; CELLS;
D O I
10.1161/JAHA.124.036082
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Abdominal aortic aneurysms (AAAs) are focal dilatations of the abdominal aorta that expand progressively, increasing their risk of rupture. Rupture of an AAA is associated with high mortality rates, but the mechanisms underlying the initiation, expansion, and rupture of AAAs are not yet fully understood. We aimed to characterize the pathophysiology of AAAs and identify new genes associated with AAA initiation and progression.Methods and Results This study used RNA sequencing data on 140 samples, becoming the largest RNA sequencing data set for differential expression studies of AAAs. We performed differential expression analyses and analyses of differential splicing between dilated and nondilated aortic tissue samples, and between AAAs of different diameters. We identified 3002 differentially expressed genes between AAAs and controls that were independent of ischemic time, 1425 of which were new. Additionally, 8 genes (EXTL3, ZFR, DUSP8, DISP1, USP33, VPS37C, ZNF784, RFX1) were differentially expressed between AAAs of varying diameters and between AAAs and control samples. Finally, 7 genes (SPP1, FHL1, GNAS, MORF4L2, HMGN1, ARL1, RNASE4) with differential splicing patterns were also differentially expressed genes between AAAs and controls, suggesting that splicing differences in these genes may contribute to the observed expression changes and disease development.Conclusions This study identifies new genes and splicing patterns associated with AAAs and validates previous relevant pathways on AAAs. These findings contribute to the understanding of the complex mechanisms underlying AAAs and may provide potential targets to limit AAA progression and mortality risk.
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页数:16
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