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Article: Differential expression of elastin assembly genes in patients with Stanford Type A aortic dissection using microarray analysis

TitleDifferential expression of elastin assembly genes in patients with Stanford Type A aortic dissection using microarray analysis
Authors
Issue Date2011
PublisherMosby, Inc. The Journal's web site is located at http://www.elsevier.com/locate/jvs
Citation
Journal Of Vascular Surgery, 2011, v. 53 n. 4, p. 1071-1078.e2 How to Cite?
AbstractObjective Pathologic studies have demonstrated that aortic dissection is initiated by an intimal tear, followed by the rapid growth of an intramural hematoma that dissects the media and is characterized by elastin degradation. Genetic extracellular matrix abnormalities and proteinases may be the predisposing factors in aortic dissection, but little is known about the role of elastic fiber assembly. Fibulin-1 is an extracellular protein that is expressed in the vascular basement membrane. It regulates elastic fiber assembly and hence provides integrity in aortic structure. This study investigates the expression profiles of genes responsible for the elastolysis in the dissected human aorta, especially those coding fibulin-1, matrix metalloproteinase-9 (MMP-9), and elastin. Methods Intraoperative aortic samples were obtained from Chinese patients with Stanford Type A aortic dissection. Both the ascending dissected aortas (primary tear) and the adjacent intact aortas were collected for comparison. Control aortic tissues were obtained from healthy organ donors. The gene profile study was determined by the Affymetrix HG-U133A GeneChip (Affymetrix, Santa Clara, Calif) and analyzed by GeneSpring GX11.0 (Agilent Technologies Inc, Palo Alto, Calif). Only the genes displaying a net signal intensity two-fold higher than the mean background were used for analysis. To evaluate elastin expression, aortic sections were stained with Movat pentachrome stain. Fibulin-1, MMP-9, and elastin mRNA and protein expression were further confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting, respectively. Results Eight male Chinese aortic dissection patients (mean age, 45.8 years) and eight gender- and age-matched organ donors were recruited for the study. On the Affymetrix platform, 2,250 of 22,283 genes (10.1%) were detectable. The dissected and adjacent macroscopically intact aorta displayed similar gene expression patterns. In contrast, 11.2% (252) of the detectable genes were differentially expressed in the dissected and control aortas. Of these, 102 genes were upregulated, and 150 genes were downregulated. Based on the gene ontology, genes that code for extracellular matrix protein components and regulating elastic fiber assembly, like fibulin-1 and elastin, were downregulated, while enzymes like MMP-9 and MMP-11 that degrade matrix proteins were upregulated in dissected aortas. RT-PCR and Western blot results further validated the results. Conclusions Our gender- and age-matched study demonstrated that the alternated genes in the elastin assembly of dissected aortas may predispose structural failure in the aorta leading to dissection. However, no significant gene alterations in the adjacent intact and dissected aortas of the same patient can be found. Therefore, the genetic changes found in the dissected aortas most likely developed before the dissection starts. The inhibition of the aberrant expression of the fibulin-1 gene and that of the related matrix proteinase may open a new avenue for preventing aortic dissection. © 2011 Society for Vascular Surgery.
Persistent Identifierhttp://hdl.handle.net/10722/133653
ISSN
2015 Impact Factor: 3.454
2015 SCImago Journal Rankings: 2.115
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheuk, BLYen_HK
dc.contributor.authorCheng, SWKen_HK
dc.date.accessioned2011-05-24T02:13:36Z-
dc.date.available2011-05-24T02:13:36Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Vascular Surgery, 2011, v. 53 n. 4, p. 1071-1078.e2en_HK
dc.identifier.issn0741-5214en_HK
dc.identifier.urihttp://hdl.handle.net/10722/133653-
dc.description.abstractObjective Pathologic studies have demonstrated that aortic dissection is initiated by an intimal tear, followed by the rapid growth of an intramural hematoma that dissects the media and is characterized by elastin degradation. Genetic extracellular matrix abnormalities and proteinases may be the predisposing factors in aortic dissection, but little is known about the role of elastic fiber assembly. Fibulin-1 is an extracellular protein that is expressed in the vascular basement membrane. It regulates elastic fiber assembly and hence provides integrity in aortic structure. This study investigates the expression profiles of genes responsible for the elastolysis in the dissected human aorta, especially those coding fibulin-1, matrix metalloproteinase-9 (MMP-9), and elastin. Methods Intraoperative aortic samples were obtained from Chinese patients with Stanford Type A aortic dissection. Both the ascending dissected aortas (primary tear) and the adjacent intact aortas were collected for comparison. Control aortic tissues were obtained from healthy organ donors. The gene profile study was determined by the Affymetrix HG-U133A GeneChip (Affymetrix, Santa Clara, Calif) and analyzed by GeneSpring GX11.0 (Agilent Technologies Inc, Palo Alto, Calif). Only the genes displaying a net signal intensity two-fold higher than the mean background were used for analysis. To evaluate elastin expression, aortic sections were stained with Movat pentachrome stain. Fibulin-1, MMP-9, and elastin mRNA and protein expression were further confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting, respectively. Results Eight male Chinese aortic dissection patients (mean age, 45.8 years) and eight gender- and age-matched organ donors were recruited for the study. On the Affymetrix platform, 2,250 of 22,283 genes (10.1%) were detectable. The dissected and adjacent macroscopically intact aorta displayed similar gene expression patterns. In contrast, 11.2% (252) of the detectable genes were differentially expressed in the dissected and control aortas. Of these, 102 genes were upregulated, and 150 genes were downregulated. Based on the gene ontology, genes that code for extracellular matrix protein components and regulating elastic fiber assembly, like fibulin-1 and elastin, were downregulated, while enzymes like MMP-9 and MMP-11 that degrade matrix proteins were upregulated in dissected aortas. RT-PCR and Western blot results further validated the results. Conclusions Our gender- and age-matched study demonstrated that the alternated genes in the elastin assembly of dissected aortas may predispose structural failure in the aorta leading to dissection. However, no significant gene alterations in the adjacent intact and dissected aortas of the same patient can be found. Therefore, the genetic changes found in the dissected aortas most likely developed before the dissection starts. The inhibition of the aberrant expression of the fibulin-1 gene and that of the related matrix proteinase may open a new avenue for preventing aortic dissection. © 2011 Society for Vascular Surgery.en_HK
dc.languageengen_US
dc.publisherMosby, Inc. The Journal's web site is located at http://www.elsevier.com/locate/jvsen_HK
dc.relation.ispartofJournal of Vascular Surgeryen_HK
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Journal of Vascular Surgery. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in PUBLICATION, VOL 53, ISSUE 4, (2011) DOI 10.1016/j.jvs.2010.11.035-
dc.titleDifferential expression of elastin assembly genes in patients with Stanford Type A aortic dissection using microarray analysisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0741-5214&volume=53&issue=4&spage=1071&epage=1078.e2&date=2011&atitle=Differential+expression+of+elastin+assembly+genes+in+patients+with+Stanford+type+A+aortic+dissection+using+microarray+analysis-
dc.identifier.emailCheuk, BLY: bernice@hku.hken_HK
dc.identifier.emailCheng, SWK: wkcheng@hkucc.hku.hken_HK
dc.identifier.authorityCheuk, BLY=rp01671en_HK
dc.identifier.authorityCheng, SWK=rp00374en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jvs.2010.11.035en_HK
dc.identifier.pmid21276682-
dc.identifier.scopuseid_2-s2.0-79953024451en_HK
dc.identifier.hkuros185307en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79953024451&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume53en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1071en_HK
dc.identifier.epage1078.e2en_HK
dc.identifier.eissn1097-6809-
dc.identifier.isiWOS:000289012600026-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheuk, BLY=7801343617en_HK
dc.identifier.scopusauthoridCheng, SWK=7404684779en_HK

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