Content and turnover of extracellular matrix protein in human “Non-specific” and inflammatory abdominal aortic aneurysms

1993 ◽  
Vol 7 (5) ◽  
pp. 546-553 ◽  
Author(s):  
Mauro Gargiulo ◽  
Andrea Stella ◽  
Michele Spina ◽  
Gianluca Faggioli ◽  
Giovanna Cenacchi ◽  
...  
2021 ◽  
Vol 22 (5) ◽  
pp. 2685
Author(s):  
Lisa Adams ◽  
Julia Brangsch ◽  
Bernd Hamm ◽  
Marcus R. Makowski ◽  
Sarah Keller

This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Anna Zampetaki ◽  
Xiaoke Yin ◽  
Ursula Mayr ◽  
Renata Gomes ◽  
Sarah Langley ◽  
...  

Rationale: Extracellular matrix (ECM) remodeling is a key function of vascular smooth muscle cells (SMCs). MicroRNAs (miRNAs), in particular the miR-29 family and miR-195, have been implicated in the control of ECM secretion. Objective: To perform a proteomics comparison of miRNA effects on ECM production by vascular SMCs. Methods and Results: Murine SMCs were transfected with miRNA mimics and antimiRs of miR-29b and miR-195, and their conditioned medium was analyzed by mass spectrometry. Both miRNAs targeted a cadre of ECM proteins, including proteoglycans, collagens, proteases, elastin and proteins associated with elastic microfibrils, albeit miR-29 showed a stronger effect. The proteomics findings were subsequently validated at the transcription level using quantitative polymerase chain reaction. Similar to miR-29, in vivo inhibition of miR-195 by intraperitoneal injection of cholesterol bound antagomiRs led to significant alterations of elastin expression in murine aortas. Since elastin degradation is a key event in aortic aneurysm formation, we investigated miR-195 expression in patients. In human aortic aneurysmal tissue, miR-195 expression was reduced compared to non-aneurysmal tissue. In plasma, a comparison between male patients with abdominal aortic aneurysms and controls matched for diabetes and hypertension returned a panel of five highly correlated miRNAs: miR-195, miR-125b, miR-148a, miR-20a and miR-340 showed significant inverse associations with the presence of abdominal aortic aneurysms and aortic diameter, with miR-195 dominating in terms of association strength. Conclusions: Using proteomic analysis, we compared the effect of miR-29 and miR-195 on ECM secretion by vascular SMCs and identified novel miRNA targets. Findings in patients support an important role for miR-195 in vascular remodeling as evidenced by reduced miR-195 expression in human aneurysmal tissue and an inverse correlation between plasma miR-195 levels and aortic diameter.


2012 ◽  
Vol 56 (5-6) ◽  
pp. 343 ◽  
Author(s):  
Athanasios Didangelos ◽  
Xiaoke Yin ◽  
Angelika Saje ◽  
Alberto Smith ◽  
Qinqbo Xu ◽  
...  

1989 ◽  
Vol 10 (4) ◽  
pp. 365-373 ◽  
Author(s):  
Robert J. Rizzo ◽  
Walter J. McCarthy ◽  
Saryu N. Dixit ◽  
Michael P. Lilly ◽  
Vera P. Shively ◽  
...  

1989 ◽  
Vol 10 (4) ◽  
pp. 0365-0373 ◽  
Author(s):  
Robert J. Rizzo ◽  
Walter J. McCarthy ◽  
Saryu N. Dixit ◽  
Michael P. Lilly ◽  
Vera P. Shively ◽  
...  

2011 ◽  
Vol 10 (8) ◽  
pp. M111.008128 ◽  
Author(s):  
Athanasios Didangelos ◽  
Xiaoke Yin ◽  
Kaushik Mandal ◽  
Angelika Saje ◽  
Alberto Smith ◽  
...  

2018 ◽  
Vol 15 (5) ◽  
pp. 367-374 ◽  
Author(s):  
Nikesh Dattani ◽  
Robert D Sayers ◽  
Matthew J Bown

Introduction: Diabetes mellitus appears to be negatively associated with abdominal aortic aneurysm; however, the mechanisms underlying this relationship remain poorly understood. The aim of this article is to provide a comprehensive review of the currently understood biological pathways underlying this relationship. Methods: A review of the literature (‘diabetes’ OR ‘hyperglycaemia’ AND ‘aneurysm’) was performed and relevant studies grouped into biological pathways. Results: This review identified a number of biological pathways through which diabetes mellitus may limit the presence, growth and rupture of abdominal aortic aneurysms. These include those influencing extracellular matrix volume, extracellular matrix glycation, the formation of advanced glycation end-products, inflammation, oxidative stress and intraluminal thrombus biology. In addition, there is an increasing evidence to suggest that the medications used to treat diabetes can also limit the development and progression of abdominal aortic aneurysms. Conclusion: The negative association between diabetes and abdominal aortic aneurysm is robust. Future studies should attempt to target the pathways identified in this review to develop novel therapeutic agents aimed at slowing or even halting aneurysm progression.


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