Rafael Almendra-Pegueros, Antonio J Barros-Membrilla, Elvira Pérez-Marlasca, Josep Julve, José Martinez-González, Cristina Rodriguez, María Galán
{"title":"确定与内质网应激和线粒体功能障碍有关的新治疗靶点,以降低退行性升主动脉瘤破裂的风险。","authors":"Rafael Almendra-Pegueros, Antonio J Barros-Membrilla, Elvira Pérez-Marlasca, Josep Julve, José Martinez-González, Cristina Rodriguez, María Galán","doi":"10.1016/j.arteri.2024.09.002","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ascending Thoracic Aortic Aneurysm (ATAA) is a progressive dilation of the aorta that can be complicated by its dissection leading to death in 80-90% of the patients. When associated with aging and atherosclerosis, the outcome is worse and reconstructive surgery is the only effective therapy. Our objective was to characterize differential expressed genes (DEG) involved in endoplasmic reticulum (ER) and mitochondria dysfunction in patients with degenerative ATAA.</p><p><strong>Methods: </strong>A transcriptomic analysis was performed by RNA sequencing using RNA isolated from ATAA of patients classified as degenerative (n=13) and multi-organ healthy donors (n=6). DEGs related to ER stress and mitochondrial dysfunction were identified with the DESeq2 package. Enriched pathway (Reactome) and protein interaction (PPI) analysis was performed with the clusterProfiles package. PPI of the selected DEGs was analyzed based on the string database and visualized by Cytoscape software.</p><p><strong>Results: </strong>Histology revealed a complete disorganization of the extracellular matrix (ECM) and cell loss in the aortic wall of ATAA patients where the upregulation of 15 DEGs and the downregulation of 13 DEGs that encode proteins related to ER stress (ATF4, EIF2AK3, HSPA5, ERN1, SEL1L), mitochondrial dysfunction (DNML1, IMMT, MT-CO3, MT-CYB, MT ND2, TIMM17B, MT-ERF1, TOMM5) and ECM was detected. The results of GO term and enriched pathway analysis indicated that these DEGs are mainly enriched in pathways related to aortic diseases.</p><p><strong>Conclusions: </strong>Our data show that proteins related to mitochondrial dysfunction and ER stress might be therapeutic targets for the treatment of ATAA.</p>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of new therapeutic targets related to endoplasmic reticulum stress and mitochondrial dysfunction to reduce the risk of rupture in degenerative ascending aortic aneurysm.\",\"authors\":\"Rafael Almendra-Pegueros, Antonio J Barros-Membrilla, Elvira Pérez-Marlasca, Josep Julve, José Martinez-González, Cristina Rodriguez, María Galán\",\"doi\":\"10.1016/j.arteri.2024.09.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Ascending Thoracic Aortic Aneurysm (ATAA) is a progressive dilation of the aorta that can be complicated by its dissection leading to death in 80-90% of the patients. When associated with aging and atherosclerosis, the outcome is worse and reconstructive surgery is the only effective therapy. Our objective was to characterize differential expressed genes (DEG) involved in endoplasmic reticulum (ER) and mitochondria dysfunction in patients with degenerative ATAA.</p><p><strong>Methods: </strong>A transcriptomic analysis was performed by RNA sequencing using RNA isolated from ATAA of patients classified as degenerative (n=13) and multi-organ healthy donors (n=6). DEGs related to ER stress and mitochondrial dysfunction were identified with the DESeq2 package. Enriched pathway (Reactome) and protein interaction (PPI) analysis was performed with the clusterProfiles package. PPI of the selected DEGs was analyzed based on the string database and visualized by Cytoscape software.</p><p><strong>Results: </strong>Histology revealed a complete disorganization of the extracellular matrix (ECM) and cell loss in the aortic wall of ATAA patients where the upregulation of 15 DEGs and the downregulation of 13 DEGs that encode proteins related to ER stress (ATF4, EIF2AK3, HSPA5, ERN1, SEL1L), mitochondrial dysfunction (DNML1, IMMT, MT-CO3, MT-CYB, MT ND2, TIMM17B, MT-ERF1, TOMM5) and ECM was detected. The results of GO term and enriched pathway analysis indicated that these DEGs are mainly enriched in pathways related to aortic diseases.</p><p><strong>Conclusions: </strong>Our data show that proteins related to mitochondrial dysfunction and ER stress might be therapeutic targets for the treatment of ATAA.</p>\",\"PeriodicalId\":45230,\"journal\":{\"name\":\"Clinica e Investigacion en Arteriosclerosis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-10-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinica e Investigacion en Arteriosclerosis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.arteri.2024.09.002\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinica e Investigacion en Arteriosclerosis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.arteri.2024.09.002","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
Identification of new therapeutic targets related to endoplasmic reticulum stress and mitochondrial dysfunction to reduce the risk of rupture in degenerative ascending aortic aneurysm.
Background: Ascending Thoracic Aortic Aneurysm (ATAA) is a progressive dilation of the aorta that can be complicated by its dissection leading to death in 80-90% of the patients. When associated with aging and atherosclerosis, the outcome is worse and reconstructive surgery is the only effective therapy. Our objective was to characterize differential expressed genes (DEG) involved in endoplasmic reticulum (ER) and mitochondria dysfunction in patients with degenerative ATAA.
Methods: A transcriptomic analysis was performed by RNA sequencing using RNA isolated from ATAA of patients classified as degenerative (n=13) and multi-organ healthy donors (n=6). DEGs related to ER stress and mitochondrial dysfunction were identified with the DESeq2 package. Enriched pathway (Reactome) and protein interaction (PPI) analysis was performed with the clusterProfiles package. PPI of the selected DEGs was analyzed based on the string database and visualized by Cytoscape software.
Results: Histology revealed a complete disorganization of the extracellular matrix (ECM) and cell loss in the aortic wall of ATAA patients where the upregulation of 15 DEGs and the downregulation of 13 DEGs that encode proteins related to ER stress (ATF4, EIF2AK3, HSPA5, ERN1, SEL1L), mitochondrial dysfunction (DNML1, IMMT, MT-CO3, MT-CYB, MT ND2, TIMM17B, MT-ERF1, TOMM5) and ECM was detected. The results of GO term and enriched pathway analysis indicated that these DEGs are mainly enriched in pathways related to aortic diseases.
Conclusions: Our data show that proteins related to mitochondrial dysfunction and ER stress might be therapeutic targets for the treatment of ATAA.
期刊介绍:
La publicación idónea para acceder tanto a los últimos originales de investigación como a formación médica continuada sobre la arteriosclerosis y su etiología, epidemiología, fisiopatología, diagnóstico y tratamiento. Además, es la publicación oficial de la Sociedad Española de Arteriosclerosis.