Microscopic multifrequency magnetic resonance elastography of ex vivo abdominal aortic aneurysms for extracellular matrix imaging in a mouse model

Abstract Vitamin D deficiency has been associated with human abdominal aortic aneurysm (AAA); however, its role in AAA pathogenesis is unclear. The aim of the present study was to investigate the effect of vitamin D deficiency on AAA development and examine if administering cholecalciferol (CCF) could limit growth of established AAA within the angiotensin-II (AngII) infused apolipoprotein E-deficient mouse model. Mice were rendered vitamin D deficiency through dietary restriction and during AngII infusion developed larger AAAs as assessed by ultrasound and ex vivo morphometry that ruptured more commonly (48% vs. 19%; P=0.028) than controls. Vitamin D deficiency was associated with increased aortic expression of osteopontin and matrix metalloproteinase-2 and -9 than controls. CCF administration to mice with established aortic aneurysms limited AAA growth as assessed by ultrasound (P<0.001) and ex vivo morphometry (P=0.036) and reduced rupture rate (8% vs. 46%; P=0.031). This effect was associated with up-regulation of circulating and aortic sclerostin. Incubation of human aortic smooth muscle cells with 1,25-dihyroxyvitamin D3 (the active metabolite of vitamin D) for 48 h induced up-regulation of sclerostin (P<0.001) and changed the expression of a range of other genes important in extracellular matrix remodeling. The present study suggests that vitamin D deficiency promotes development of large rupture-prone aortic aneurysms in an experimental model. CCF administration limited both growth and rupture of established aneurysms. These effects of vitamin D appeared to be mediated via changes in genes involved in extracellular matrix remodeling, particularly sclerostin.

Download Full-text

Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights

International Journal of Molecular Sciences ◽

10.3390/ijms22052685 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2685

Author(s):

Lisa Adams ◽

Julia Brangsch ◽

Bernd Hamm ◽

Marcus R. Makowski ◽

Sarah Keller

Keyword(s):

Extracellular Matrix ◽

Molecular Imaging ◽

Molecular Targets ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Type I ◽

Target Tissue ◽

Pharmacologic Treatment ◽

Abdominal Aortic

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.

Download Full-text

Commentary on ‘Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms’

European Journal of Vascular and Endovascular Surgery ◽

10.1016/j.ejvs.2016.01.004 ◽

2016 ◽

Vol 51 (4) ◽

pp. 527

Author(s):

A. Chaudhuri

Keyword(s):

Magnetic Resonance Imaging ◽

Positron Emission Tomography ◽

Magnetic Resonance ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Emission Tomography ◽

Resonance Imaging ◽

Cellular Inflammation ◽

Positron Emission ◽

Abdominal Aortic

Download Full-text

Magnetic resonance angiography in the preoperative evaluation of abdominal aortic aneurysms

Annals of Emergency Medicine ◽

10.1016/s0196-0644(05)83905-8 ◽

1994 ◽

Vol 23 (1) ◽

pp. 143-144

Author(s):

Eric Legome

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Angiography ◽

Preoperative Evaluation ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Abdominal Aortic

Download Full-text

Comparison of ultrasonography, computed tomography and magnetic resonance imaging with intraoperative measurements in the evaluation of abdominal aortic aneurysms

Clinics ◽

10.1590/s1807-59322005000100006 ◽

2005 ◽

Vol 60 (1) ◽

pp. 21-28 ◽

Cited By ~ 4

Author(s):

Francisco das Chagas de Azevedo ◽

Antonio Eduardo Zerati ◽

Roberto Blasbalg ◽

Nelson Wolosker ◽

Pedro Puech-Leão

Keyword(s):

Magnetic Resonance Imaging ◽

Computed Tomography ◽

Magnetic Resonance ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Resonance Imaging ◽

Abdominal Aortic

Download Full-text

Abstract 496: Extracellular Matrix Secretion by Vascular Smooth Muscle Cells: Role of MiR-195 and MiR-29b

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.496 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Anna Zampetaki ◽

Xiaoke Yin ◽

Ursula Mayr ◽

Renata Gomes ◽

Sarah Langley ◽

...

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Abdominal Aortic ◽

Vascular Smcs

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.

Download Full-text