Expression and role of lumican in acute aortic dissection: A human and mouse study

Autor: Ming-En Hsu, Chien-Te Ho, Victor Chien-Chia Wu, Ying-Chang Tung, Winston W.-Y. Kao, Shao-Wei Chen, Pao-Hsien Chu, Fu-Chih Hsiao, Shing-Hsien Chou, Yi-Hsin Chan, An-Hsun Chou, Pyng-Jing Lin
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Pathology
Cell signaling
Lumican
Pathogenesis
Kaplan-Meier Estimate
Smad2 Protein
030204 cardiovascular system & hematology
Signal transduction
Pathology and Laboratory Medicine
Biochemistry
Vascular Medicine
Aortic aneurysm
Mice
0302 clinical medicine
Transforming Growth Factor beta
Medicine and Health Sciences
Group-Specific Staining
Enzyme-Linked Immunoassays
Aorta
Aortic dissection
Staining
Mice
Knockout
Multidisciplinary
Angiotensin II
Incidence
Signaling cascades
Animal Models
Up-Regulation
medicine.anatomical_structure
Experimental Organism Systems
Acute Disease
cardiovascular system
Medicine
Anatomy
Aneurysms
Research Article
medicine.medical_specialty
Cell biology
Science
Aortic Rupture
Connective tissue
Mouse Models
Research and Analysis Methods
03 medical and health sciences
Model Organisms
medicine.artery
medicine
Animals
Humans
Vascular Diseases
Aortic rupture
Immunoassays
business.industry
Hematoxylin Staining
Biology and Life Sciences
medicine.disease
Mice
Inbred C57BL
Aortic Dissection
Disease Models
Animal
030104 developmental biology
TGF-beta signaling cascade
Specimen Preparation and Treatment
Aminopropionitrile
Chronic Disease
Cardiovascular Anatomy
Animal Studies
Immunologic Techniques
Blood Vessels
business
Biomarkers
Zdroj: PLoS ONE
PLoS ONE, Vol 16, Iss 7, p e0255238 (2021)
ISSN: 1932-6203
Popis: Introduction Aortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model. Methods LUM expression patterns were analyzed using aortic tissues of AD patients, and serum soluble LUM (s-LUM) levels were compared between patients with acute AD (AAD) and chronic AD (CAD). Lum-knockout (Lum−/−) mice were challenged with β-aminopropionitrile (BAPN) and angiotensin II (Ang II) to induce AD. The survival rate, AD incidence, and aortic aneurysm (AA) in these mice were compared with those in BAPN–Ang II–challenged wildtype (WT) mice. Tgf-β/Smad2, Mmps, Lum, and Nox expression patterns were examined. Results LUM expression was detected in the intima and media of the ascending aorta in patients with AAD. Serum s-LUM levels were significantly higher in patients with AAD than CAD. Furthermore, AD-associated mortality and thoracic aortic rupture incidence were significantly higher in the Lum−/− AD mice than in the WT AD mice. However, no significant pathologic changes in AA were observed in the Lum−/− AD mice compared with the WT AD mice. The BAPN–Ang II–challenged WT and Lum−/− AD mice had higher Tgf-β, p-Smad2, Mmp2, Mmp9, and Nox4 levels than those of non-AD mice. We also found that Lum expression was significantly higher in the BAPN-Ang II–challenged WT in comparison to the unchallenged WT mice. Conclusion LUM expression was altered in patients with AD display increased s-LUM in blood, and Lum−/− mice exhibited augmented AD pathogenesis. These findings support the notion that LUM is a biomarker signifying the pathogenesis of injured aorta seen in AAD. The presence of LUM is essential for maintenance of connective tissue integrity. Future studies should elucidate the mechanisms underlying LUM association in aortic changes.
Databáze: OpenAIRE
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