A comparison of balloon injury models of endovascular lesions in rat arteries

Gabeler, Edward E.E.; Hillegersberg, Richard van; Eps, Randolph G. Statius van; Sluiter, Wim J.; Gussenhoven, Elma J.; Mulder, Paul; Urk, Hero van

doi:10.1186/1471-2261-2-16

Cited by 33 publications

(31 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…in saline daily until the end of the experiment. Balloon injury in the right iliac artery was inflicted with a 2F Fogarty catheter (Baxter) adapted to a custom angiographic kit (Boston Scientific, Scimed) [41]. An aortotomy in the abdominal aorta was made to insert a catheter to the level of the right iliac artery.…”

Section: Methodsmentioning

confidence: 99%

Small molecule agonists of integrin CD11b/CD18 do not induce global conformational changes and are significantly better than activating antibodies in reducing vascular injury

Faridi

Altintas

Gomez

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

BACKGROUND CD11b/CD18 is a key adhesion receptor that mediates leukocyte adhesion, migration and immune functions. We recently identified novel compounds, leukadherins, that allosterically enhance CD11b/CD18-dependent cell adhesion and reduce inflammation in vivo, suggesting integrin activation to be a novel mechanism of action for the development of anti-inflammatory therapeutics. Since a number of well-characterized anti-CD11b/CD18 activating antibodies are currently available, we wondered if such biological agonists could also become therapeutic leads following this mechanism of action. METHODS We compared the two types of agonists using in vitro cell adhesion and wound-healing assays and using animal model systems. We also studied effects of the two types of agonists on outside-in signaling in treated cells. RESULTS Both types of agonists similarly enhanced integrin-mediated cell adhesion and decreased cell migration. However, unlike leukadherins, the activating antibodies produced significant CD11b/CD18 macro clustering and induced phosphorylation of key proteins involved in outside-in signaling. Studies using conformation reporter antibodies showed that leukadherins did not induce global conformational changes in CD11b/CD18 explaining the reason behind their lack of ligand-mimetic outside-in signaling. In vivo, leukadherins reduced vascular injury in a dose-dependent fashion, but, surprisingly, the anti-CD11b activating antibody ED7 was ineffective. CONCLUSIONS Our results suggest that small molecule allosteric agonists of CD11b/CD18 have clear advantages over the biologic activating antibodies and provide a mechanistic basis for the difference. GENERAL SIGNIFICANCE CD11b/CD18 activation represents a novel strategy for reducing inflammatory injury. Our study establishes small molecule leukadherins as preferred agonists over activating antibodies for future development as novel anti-inflammatory therapeutics.

show abstract

Section: Methodsmentioning

confidence: 99%

Small molecule agonists of integrin CD11b/CD18 do not induce global conformational changes and are significantly better than activating antibodies in reducing vascular injury

Faridi

Altintas

Gomez

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

show abstract

“…The impact of aging on vascular remodeling was evaluated using the rat balloon injury model (11). First, we proved that arterial damage was inflicted to the same degree in arteries of aged and young rats regardless of the size of the vessel.…”

Section: Aging Increases Postinjury Neointimal Hyperplasia In Ratsmentioning

confidence: 96%

“…All operative procedures were performed while the animals were under isoflurane anesthesia (Baxter, Irvine, CA). A balloon injury was inflicted in the right iliac artery with a 2F Fogarty catheter (Baxter) adapted to a custom angiographic kit (Boston Scientific, Scimed) (11). The balloon catheter was always inflated to yield a constant pressure between 1.5 and 1.6 atmospheres.…”

mentioning

confidence: 99%

Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling

Rodriguez-Menocal

Faridi

Martinez

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Padron RI. Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling. Am J Physiol Heart Circ Physiol 306: H641-H653, 2014. First published January 10, 2014; doi:10.1152/ajpheart.00641.2013.-Aging has been associated with pathological vascular remodeling and increased neointimal hyperplasia. The understanding of how aging exacerbates this process is fundamental to prevent cardiovascular complications in the elderly. This study proposes a mechanism by which aging sustains leukocyte adhesion, vascular inflammation, and increased neointimal thickness after injury. The effect of aging on vascular remodeling was assessed in the rat balloon injury model using microarray analysis, immunohistochemistry, and LINCOplex assays. The injured arteries in aging rats developed thicker neointimas than those in younger animals, and this significantly correlated with a higher number of tissue macrophages and increased vascular IL-18. Indeed, IL-18 was 23-fold more abundant in the injured vasculature of aged animals compared with young rats, while circulating levels were similar in both groups of animals. The depletion of macrophages in aged rats with clodronate liposomes ameliorated vascular accumulation of IL-18 and significantly decreased neointimal formation. IL-18 was found to inhibit apoptosis of vascular smooth muscle cells (VSMC) and macrophages, thus favoring both the formation and inflammation of the neointima. In addition, injured arteries of aged rats accumulated 18-fold more fibrinogen-␥ than those of young animals. Incubation of rat peritoneal macrophages with immobilized IL-18 increased leukocyte adhesion to fibrinogen and suggested a proinflammatory positive feedback loop among macrophages, VSMC, and the deposition of fibrinogen during neointimal hyperplasia. In conclusion, our data reveal that concentration changes in vascular cytokine and fibrinogen following injury in aging rats contribute to local inflammation and postinjury neointima formation. inflammation; vascular injury; aging; neointima; vascular smooth muscle cells AGING IS RECOGNIZED AS A MAJOR and independent risk factor for the development of vascular restenosis (29). This risk can be explained by profound, age-dependent changes in vascular structure and physiology that lead to endothelial dysfunction (18) and a chronic inflammatory stage (53), which impair healing and render a vascular system prone to develop occlusive neointimas in response to injury. However, even when this notion is largely accepted, the mechanisms by which aging alters vascular physiology and repair have remained understudied to date.The process of aging increases and sustains inflammation within the vascular wall (52). Macrophages are commonly recognized as the most important cell type in the chronicity of this process (37). Indeed, inflammation in arteries of aged individuals is evidenced by an excessive accumulation of macrophages in the inner layer of the arterial wall (intima), and this occurs in the presence o...

show abstract

“…All operative procedures were under isoflurane anesthesia (Baxter, IL). Balloon injury in the right iliac artery was inflicted with a 2F Fogarty catheter (Baxter, Irvine, CA) adapted to a custom angiographic kit (Boston Scientific, Scimed) (16). The balloon catheter was always inflated to yield a constant pressure between 1.5-1.6 atmospheres.…”

Section: Methodsmentioning

confidence: 99%

Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

Khan

Pham²,

Wei³

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Vazquez-Padron RI. Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature. Am J Physiol Heart Circ Physiol 298: H66 -H74, 2010. First published October 23, 2009 doi:10.1152/ajpheart.00501.2009This study aims to demonstrate the role of stress-induced senescence in aged-related neointimal formation. We demonstrated that aging increases senescence-associated ␤-galactosidase activity (SA-␤-Gal) after vascular injury and the subsequent neointimal formation (neointima-to-media ratio: 0.8 Ϯ 0.2 vs. 0.54 Ϯ 0.15) in rats. We found that senescent cells (SA-␤-Gal ϩ p21 ϩ ) were scattered throughout the media and adventitia of the vascular wall at day 7 after injury and reached their maximum number at day 14. However, senescent cells only persisted in the injured arteries of aged animals until day 30. No senescent cells were observed in the noninjured, contralateral artery. Interestingly, vascular senescent cells accumulated genomic 8-oxo-7,8-dihydrodeoxyguanine, indicating that these cells were under intense oxidative stress. To demonstrate whether senescence worsens intimal hyperplasia after injury, we seeded matrigel-embedded senescent and nonsenescent vascular smooth muscle cells around injured vessels. The neointima was thicker in arteries treated with senescent cells with respect to those that received normal cells (neointima-to-media ratio: 0.41 Ϯ 0.105 vs. 0.26 Ϯ 0.04). In conclusion, these results demonstrate that vascular senescence is not only a consequence of postinjury oxidative stress but is also a worsening factor for neointimal development in the aging vasculature. vascular injury; aging; neointima; vascular smooth muscle cells THE MECHANISM BY WHICH AGING exaggerates neointima formation after vascular injury has, so far, remained elusive (40, 42). It is known that aging alters vascular physiology (3) and arterial response to oxidative stress and injury (6, 35). One of the physiological changes that aging promotes, senescence, has recently been found to be involved in the development of cardiovascular diseases (14, 29 -31). During senescence, cells undergo changes in morphology, physiology, and gene expression and permanently cease to proliferate but remain metabolically active for a long period of time (17,19,22,41). A variety of physiological stimuli can provoke a cell to enter senescence. A few examples include telomere shortening (8, 39), oxidative stress (9, 12, 13), and activation of oncogenes (2,32,33).Experimental evidences suggest the contribution of senescent cells to the development of vascular proliferative diseases. Human atherosclerotic plaques showed abundance of SA-␤- (26), and fibroblasts (7) produce de novo growth factors that may promote nearby cell growth and inflammation. Despite of all of these evidences, the role of senescence in neointimal formation has remained poorly understood. Herein, we investigate the role of senescence in postinjury neointimal formation using the rat model of arterial balloon injury. We have found that aging exacerbates o...

show abstract

A comparison of balloon injury models of endovascular lesions in rat arteries

Cited by 33 publications

References 24 publications

Small molecule agonists of integrin CD11b/CD18 do not induce global conformational changes and are significantly better than activating antibodies in reducing vascular injury

Small molecule agonists of integrin CD11b/CD18 do not induce global conformational changes and are significantly better than activating antibodies in reducing vascular injury

Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling

Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

Contact Info

Product

Resources

About