Specific adhesion and accumulation of VCAM-1-targeted ultrasound microbubbles to inflammatory endothelial cells under hemodynamic shear flow simulation

Yang, Hong; Zhang, Lie; Xiong, Xiaoyang; Liu, Yiyao

doi:10.1016/j.jconrel.2011.09.027

Cited by 2 publications

(2 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VCAM-1 is known to be involved in this recruitment of inflammatory cells, as it is a protein that is involved in the adherence of these cells to the endothelial layer of vessel walls. Hence, VCAM-1 promotes attachment to vessel walls and entry within the inner architecture of the vessel of inflammatory cells and oxidized LDL cholesterol particles 4. This begets even further release of cytokine-signaling molecules that recruit more inflammatory cells.…”

Section: Atherosclerosis Pathogenesis: a Brief Summarymentioning

confidence: 99%

Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms

Vacek

Rehman

Neamtu

et al. 2015

VHRM

122

View full text Add to dashboard Cite

Atherosclerosis is an inflammatory process that involves activation of matrix metalloproteinases (MMPs); MMPs degrade collagen and allow for smooth-muscle cell migration within a vessel. Moreover, this begets an accumulation of other cellular material, resulting in occlusion of the vessel and ischemic events to tissues in need of nutrients. Homocysteine has been shown to activate MMPs via an increase in oxidative stress and acting as a signaling molecule on receptors like the peroxisome proliferator activated receptor-γ and N-methyl-D-aspartate receptor. Nitric oxide has been shown to be beneficial in some cases of deactivating MMPs. However, in other cases, it has been shown to be harmful. Further studies are warranted on the scenarios that are beneficial versus destructive. Hydrogen sulfide (H2S) has been shown to decrease MMP activities in all cases in the literature by acting as an antioxidant and vasodilator. Various MMP-knockout and gene-silencing models have been used to determine the function of the many different MMPs. This has allowed us to discern the role that each MMP has in promoting or alleviating pathological conditions. Furthermore, there has been some study into the MMP polymorphisms that exist in the population. The purpose of this review is to examine the role of MMPs and their polymorphisms on the development of atherosclerosis, with emphasis placed on pathways that involve nitric oxide, hydrogen sulfide, and homocysteine.

show abstract

Section: Atherosclerosis Pathogenesis: a Brief Summarymentioning

confidence: 99%

Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms

Vacek

Rehman

Neamtu

et al. 2015

VHRM

122

View full text Add to dashboard Cite

show abstract

“…In a recent study in non-human primates with diet-induced obesity, a progressive increase in endothelial activation over the time could be demonstrated using P-selectin and VCAM-1 targeted microbubbles [47]. The specific binding and accumulation of VCAM-1 targeted microbubbles even under shear flow conditions has been simulated in several in vitro models [48]. …”

Section: Future Perspectives: Molecular Contrast Ultrasound Imagingmentioning

confidence: 99%

Molecular Imaging of Carotid Plaque Vulnerability

2014

View full text Add to dashboard Cite

Background: Carotid endarterectomy (CEA) has been shown to be beneficial in patients with high-grade symptomatic carotid artery stenosis. Patients with high-grade asymptomatic stenosis may only exceptionally benefit from CEA during periods of increased plaque vulnerability. Imaging modalities to characterize unstable, vulnerable plaques are strongly needed for better risk stratification in these patients. Summary: Contrast-enhanced ultrasound (CEUS) is a novel and noninvasive technique capable to identify several surrogate markers of vulnerable carotid plaques. The use of specific ultrasound microbubbles allows a reliable detection of microulcerations due to an optimized visualization of the plaque-lumen border. As microbubbles are strictly intravascular tracers, the detection of individual microbubbles within the plaque corresponds to intraplaque neovessels. The accuracy of CEUS in the visualization of newly formed microvessels has been confirmed in histological studies on carotid endarterectomy specimens. Together with the formation of adventitial vasa vasorum, intraplaque neovascularization is a strong predictor for symptomatic disease. The phenomenon of late phase contrast enhancement is based on the adherence of microbubble-containing monocytes on inflamed endothelium. Recent studies suggest that late phase contrast enhancement may reflect endothelial inflammation or activation within carotid plaques. The development of conjugated microbubbles that bind to specific ligands such as thrombotic material or neovessels has led to the term ‘molecular imaging'. CEUS with microbubbles targeted to P-selectin and VCAM-1, key molecules in leukocyte trafficking, was used to detect an inflammatory plaque phenotype, whereas microbubbles coupled to the VEGF-receptor may allow for a detection of neovascularization. Even though imaging with targeted microbubbles is yet in an experimental stage, this technique can visualize active plaque reorganization with increased vulnerability leading to generation of arterio-arterial embolism. Key Messages: The use of contrast-enhanced ultrasound can be recommended to assess atherosclerotic carotid lesions at risk for rupture. Prospective clinical studies are needed to validate the use of CEUS in patients with high risks of recurrent large artery strokes. In particular, this applies to the detection of intraplaque neovascularization, a well-established marker in preclinical and observational studies, while the clinical significance of late phase contrast enhancement still needs to be determined.

show abstract

Specific adhesion and accumulation of VCAM-1-targeted ultrasound microbubbles to inflammatory endothelial cells under hemodynamic shear flow simulation

Cited by 2 publications

References 5 publications

Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms

Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms

Molecular Imaging of Carotid Plaque Vulnerability

Contact Info

Product

Resources

About