Mature endothelial cell therapy stabilizes abdominal aortic aneurysm through paracrine mechanisms and recruitment of local vascular cells

2012 ◽  
Vol 56 (5-6) ◽  
pp. 342
Author(s):  
Grégory Franck ◽  
Jianping Dai ◽  
Stéphanie Michineau ◽  
Saravath Ngo ◽  
Anne-Marie Guinault ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Endothelial Cell ◽  
Aortic Aneurysm ◽  
Cell Therapy ◽  
Vascular Cells ◽  
Mature Endothelial Cell ◽  
Abdominal Aortic

Abstract 295: The Stem Cell Therapy to Prevent Expansion of Abdominal Aortic Aneurysm (STOP-AAA) Trial: Rationale and Design

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Michael P Murphy ◽  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cell Therapy ◽  
Autologous Bone Marrow ◽  
Research Network ◽  
Stem Cell Population ◽  
Abdominal Aortic ◽  
Autologous Bone

Background: Abdominal aortic aneurysm (AAA) is the 13 th leading cause of death in the United States. The only options for treatment at present for AAA are open surgical and endovascular repair, both of which are associated with significant morbidity, mortality, and expense.Thus AAA represents an unmet medical need. AAA pathogenesis is a multifactorial inflammatory process characterized by activation of T-cells,macrophages and neutrophils resulting in degradation of the aortic wall. Mesenchymal stromal cells (MSCs) suppress T-cell and macrophage activation, inhibit matrix metalloproteinases and have been shown to decrease aneurysm expansion in murine models. Methods: The STOP-AAA trial, from the NHLBI funded Cardiovascular Cell Therapy Research Network, is a randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of autologous bone marrow derived MSCs in suppressing expansion of small AAA (35-50mm).Forty patients will be randomized in a 1:1 fashion to receive systemic administration of placebo or 3 doses of 2x10 6 MSC/kg. at baseline, 24, and 52 weeks. The primary endpoint will be change in AAA diameter at 18 months as measured by a single blinded observer using contrast enhanced helical computed tomographic angiography (CTA).The secondary endpoints include time to elective repair, incidence of AAA related deaths and rupture,change in aortic mural inflammation at 18 months as quantified by F18-fluorodeoxyglucose (FDG) uptake with integrated positron emission tomography and computed tomography (PET/CT), changes in circulating mRNA, microRNA, and inflammatory cell profiles, changes in serum cytokine levels, and major adverse cardiac events. Conclusion: The STOP-AAA will be the first in man study to assess the efficacy of autologous bone marrow derived MSCs to suppress AAA expansion. Furthermore the data collected from this novel trial will provide unique mechanistic insights in the immunomodulatory properties of this stem cell population.

scholarly journals Endothelial Cell Tetrahydrobiopterin Modulates Sensitivity to Ang (Angiotensin) II–Induced Vascular Remodeling, Blood Pressure, and Abdominal Aortic Aneurysm

Hypertension ◽  
2018 ◽  
Vol 72 (1) ◽  
pp. 128-138 ◽  
Author(s):  
Surawee Chuaiphichai ◽  
Victoria S. Rashbrook ◽  
Ashley B. Hale ◽  
Lucy Trelfa ◽  
Jyoti Patel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Abdominal Aortic Aneurysm ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Vascular Remodeling ◽  
Abdominal Aortic

Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells

2006 ◽  
Vol 184 (2) ◽  
pp. 302-311 ◽  
Author(s):  
Jian Liu ◽  
Galina K. Sukhova ◽  
Jin-Tian Yang ◽  
Jiusong Sun ◽  
Likun Ma ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cathepsin L ◽  
Vascular Cells ◽  
Abdominal Aortic

Abstract 15302: Deficiency of Myeloid Membrane-bound Thrombomodulin Attenuates Vascular Inflammation in Abdominal Aortic Aneurysm

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Hua-Lin Wu ◽  
Kuan-Chieh Wang ◽  
Guey-Yueh Shi
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Endothelial Cell ◽  
Aortic Aneurysm ◽  
Vascular Inflammation ◽  
Ros Production ◽  
Wild Type ◽  
Abdominal Aortic ◽  
Membrane Bound ◽  
Deficient Mice ◽  
Endothelial Cell Adhesion

Introduction: Thrombomodulin (TM), a glycoprotein predominantly expressed in endothelial cells, has been well known for its anti-coagulant and anti-inflammatory properties. Paradoxically, we recently found a promoting role of monocytic membrane-bound TM in experimental sepsis. Hypothesis: We assessed the hypothesis that membrane-bound TM may participate in vascular inflammation and the development of abdominal aortic aneurysm (AAA). Methods and Results: Characterization of the CaCl 2 -induced AAA in mice revealed that TM expression was mainly localized in vascular smooth muscle cells (VSMCs) and infiltrating macrophages. To investigate the function of membrane-bound TM in vivo, transgenic mice with myeloid- (LysMcre/TM flox/flox ) and VSMC-specific (SM22-cre tg /TM flox/flox ) TM ablation and their wild type counterparts were generated. In the CaCl 2 -induced AAA model, myeloid TM-deficient mice (n=12) but not VSMC TM-deficient mice (n=8), when compared with their wild-type respective controls (TM flox/flox , SM22-cre tg /TM +/+ ), showed attenuated accumulation of macrophages, reduced production of proinflammatory cytokines and suppressed levels of matrix metalloproteinase-9, thereby preventing progressive aortic dilatation. In vitro TM-deficient macrophages had reduced proinflammatory mediator production, macrophage-endothelial cell adhesion and intracellular oxidative stress (e.g., reactive oxygen species [ROS]) versus TM wild-type macrophages. In addition, deficiency of TM in hyperlipidemic mice (ApoE -/- /LysMcre/TM flox/flox , n=9) conferred protection against angiotensin II-infused AAA, compatible with dramatically diminished aortic ROS production and matrix metalloproteinase activities. Finally, human AAA samples (n=6) showed that TM signals were predominantly localized to infiltrating macrophages, implicating the potential involvement of monocytic membrane-bound TM in human diseases. Conclusion: Membrane-bound TM in macrophages plays a critical role in the development of AAA by enhancing macrophage-endothelial cell adhesion, proinflammatory mediator elaboration and intracellular ROS production.

Current evidence and prospects for medical treatment of abdominal aortic aneurysms

VASA ◽  
2005 ◽  
Vol 34 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Diehm ◽  
Schmidli ◽  
Dai-Do ◽  
Baumgartner
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Medical Treatment ◽  
Endovascular Treatment ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Current Evidence ◽  
Significant Morbidity ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Abdominal aortic aneurysm (AAA) is a potentially fatal condition with risk of rupture increasing as maximum AAA diameter increases. It is agreed upon that open surgical or endovascular treatment is indicated if maximum AAA diameter exceeds 5 to 5.5cm. Continuing aneurysmal degeneration of aortoiliac arteries accounts for significant morbidity, especially in patients undergoing endovascular AAA repair. Purpose of this review is to give an overview of the current evidence of medical treatment of AAA and describe prospects of potential pharmacological approaches towards prevention of aneurysmal degeneration of small AAAs and to highlight possible adjunctive medical treatment approaches after open surgical or endovascular AAA therapy.

Influence of preoperative statins and aspirin administration on biological and magnetic resonance imaging properties in patients with abdominal aortic aneurysm

VASA ◽  
2020 ◽  
pp. 1-9
Author(s):  
Milos Sladojevic ◽  
Petar Zlatanovic ◽  
Zeljka Stanojevic ◽  
Igor Koncar ◽  
Sasenka Vidicevic ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Abdominal Aortic Aneurysm ◽  
Magnetic Resonance ◽  
Aortic Aneurysm ◽  
Signal Intensity ◽  
Psoas Muscle ◽  
Resonance Imaging ◽  
Maximal Diameter ◽  
Aneurysm Wall ◽  
Abdominal Aortic

Summary: Background: Main objective of this study was to evaluate the influence of statins and/or acetylsalicylic acid on biochemical characteristics of abdominal aortic aneurysm (AAA) wall and intraluminal thrombus (ILT). Patients and methods: Fifty patients with asymptomatic infrarenal AAA were analyzed using magnetic resonance imaging on T1w sequence. Relative ILT signal intensity (SI) was determined as a ratio between ILT and psoas muscle SI. Samples containing the full ILT thickness and aneurysm wall were harvested from the anterior surface at the level of the maximal diameter. The concentration of enzymes such as matrix metalloproteinase (MMP) 9, MMP2 and neutrophil elastase (NE/ELA) were analyzed in ILT and AAA wall; while collagen type III, elastin and proteoglycan 4 were analyzed in harvested AAA wall. Oxidative stress in the AAA wall was assessed by catalase and malondialdehyde activity in tissue samples. Results: Relative ILT signal intensity (1.09 ± 0.41 vs 0.89 ± 0.21, p = 0.013) were higher in non-statin than in statin group. Patients who were taking aspirin had lower relative ILT area (0.89 ± 0.19 vs 1.13. ± 0.44, p = 0.016), and lower relative ILT signal intensity (0.85 [0.73–1.07] vs 1.01 [0.84–1.19], p = 0.021) compared to non-aspirin group. There were higher concentrations of elastin in AAA wall among patients taking both of aspirin and statins (1.21 [0.77–3.02] vs 0.78 (0.49–1.05) ng/ml, p = 0.044) than in patients who did not take both of these drugs. Conclusions: Relative ILT SI was lower in patients taking statin and aspirin. Combination of antiplatelet therapy and statins was associated with higher elastin concentrations in AAA wall.

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