Molecular Magnetic Resonance Imaging of Myocardial Angiogenesis After Acute Myocardial Infarction

Oostendorp, M. van; Douma, Kim; Wagenaar, Allard; Slenter, Jos; Hackeng, Tilman M.; Zandvoort, Marc A. M. J. van; Post, Mark J.; Backes, Walter H.

doi:10.1161/circulationaha.109.889451

Cited by 59 publications

(51 citation statements)

References 38 publications

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“…to stimulate angiogenesis. Attractive targets might be CD13 and α v β 3 integrins expressed on angiogenic blood vessels, which can be used to direct liposomes containing pro-angiogenic or anti-inflammatory drugs to the endothelium [37,38].…”

Section: Discussionmentioning

confidence: 99%

Distribution of lipid-based nanoparticles to infarcted myocardium with potential application for MRI-monitored drug delivery

Paulis

Geelen

Kuhlmann

et al. 2012

Journal of Controlled Release

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Section: Discussionmentioning

confidence: 99%

Distribution of lipid-based nanoparticles to infarcted myocardium with potential application for MRI-monitored drug delivery

Paulis

Geelen

Kuhlmann

et al. 2012

Journal of Controlled Release

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“…Multiphoton laser scanning microscopy (MPLSM) can overcome these shortcomings and has previously been used for in situ imaging of healthy and atherosclerotic arteries at subcellular resolution, 24,25 as well as for quantifying angiogenic activity in models of tumor vascularization and myocardial infarction. 26,27 In addition, MPLSM has been used to image large blood vessels in vivo, triggered on heart rate and respiration to reduce motion artifacts. 28,29 More recently, MPLSM was used to quantify blood flow and hematocrit in blood vessels, 30 substantiating MPLSM as a valuable tool for functional studies of the (micro)vasculature.…”

Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Plaque-Associated Vasa Vasorum in Aged Apolipoprotein E–Deficient Mice Exhibit Proatherogenic Functional Features In Vivo

Rademakers

Douma

Hackeng

et al. 2013

ATVB

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Objective-Neovascularization of human atherosclerotic plaques is implicated in plaque progression and destabilization, although its functional implications are yet unresolved. Here, we aimed to elucidate functional and morphological properties of plaque microvessels in mice in vivo. Methods and Results-Atherosclerotic carotid arteries from aged (>40 weeks) apolipoprotein E-deficient mice were imaged in vivo using multiphoton laser scanning microscopy. Two distinct groups of vasa vasorum microvessels were observed at sites of atherosclerosis development (median diameters of 18.5 and 5.9 μm, respectively), whereas microvessels within the plaque could only rarely be found. In vivo imaging showed ongoing angiogenic activity and injection of fluorescein isothiocyanate-dextran confirmed active perfusion. Plaque vasa vasorum showed increased microvascular leakage, combined with a loss of endothelial glycocalyx. Mean blood flow velocity in plaque-associated vasa vasorum was reduced by ±50% compared with diameter-matched control capillaries, whereas mean blood flow was reduced 8-fold. Leukocyte adhesion and extravasation were increased 6-fold in vasa vasorum versus control capillaries. Conclusion-Using a novel in vivo functional imaging strategy, we showed that plaque-associated vasa vasorum were angiogenically active and, albeit poorly, perfused. Moreover, plaque-associated vasa vasorum showed increased permeability, reduced blood flow, and increased leukocyte adhesion and extravasation (ie, characteristics that could contribute to plaque progression and destabilization). Key Words: angiogenesis ◼ atherosclerosis ◼ in vivo imaging ◼ microcirculation ◼ multiphoton laser scanning microscopy

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“…Molecular MRI of angiogenesis has been successfully performed in animal models of different pathologies, including cancer (26,27), atherosclerosis (28) and myocardial infarction (29,30). These studies have applied different types of MRI contrast agents, for example based on gadolinium (26,28,29), iron oxides (27) or perfluorocarbons (31), with conjugated targeting ligands ranging from small peptides to big antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…These studies have applied different types of MRI contrast agents, for example based on gadolinium (26,28,29), iron oxides (27) or perfluorocarbons (31), with conjugated targeting ligands ranging from small peptides to big antibodies. To our knowledge, there have been no reports of molecular MRI of angiogenesis after stroke.…”

Section: Discussionmentioning

confidence: 99%

PECAM‐1‐targeted micron‐sized particles of iron oxide as MRI contrast agent for detection of vascular remodeling after cerebral ischemia

Deddens

Tilborg

Toorn

et al. 2013

Contrast Media & Molecular

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An increasing amount of studies have provided evidence for vascular remodeling, for example, angiogenesis, after cerebral ischemia, which may play a significant role in post-stroke brain plasticity and recovery. Molecular imaging can provide unique in vivo whole-brain information on alterations in the expression of specific endothelial markers. A possible target for molecular magnetic resonance imaging (MRI) of post-stroke (neo)vascularization is platelet endothelial cell adhesion molecule-1 (PECAM-1). Here we describe significantly increased PECAM-1 mRNA levels in ipsilesional brain tissue at 6 h, 24 h and 3 days after transient middle cerebral artery occlusion in mice, and elevated PECAM-1 staining throughout the lesion at 3, 7 and 21 days post-stroke. The potential of micron-sized particles of iron oxide (MPIO) conjugated with PECAM-1-targeted antibodies, that is, αPECAM-1-MPIO, to expose stroke-induced PECAM-1 upregulation with molecular MRI was assessed. In vitro studies demonstrated that PECAM-1-expressing brain endothelial cells could be effectively labeled with αPECAM-1-MPIO, giving rise to a fourfold increase in MRI relaxation rate R2. Injection of near-infrared fluorescent dye-labeled αPECAM-1 showed target specificity and dose efficiency of the antibody for detection of brain endothelial cells at 3 days post-stroke. However, in vivo molecular MRI at 3 and 7 days after stroke revealed no αPECAM-1-MPIO-based contrast enhancement, which was corroborated by the absence of αPECAM-1-MPIO in post mortem brain tissue. This indicates that this molecular MRI approach, which has been proven successful for in vivo detection of other types of cell adhesion molecules, is not invariably effective for MRI-based assessment of stroke-induced alterations in expression of cerebrovascular markers.

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Molecular Magnetic Resonance Imaging of Myocardial Angiogenesis After Acute Myocardial Infarction

Cited by 59 publications

References 38 publications

Distribution of lipid-based nanoparticles to infarcted myocardium with potential application for MRI-monitored drug delivery

Distribution of lipid-based nanoparticles to infarcted myocardium with potential application for MRI-monitored drug delivery

Plaque-Associated Vasa Vasorum in Aged Apolipoprotein E–Deficient Mice Exhibit Proatherogenic Functional Features In Vivo

PECAM‐1‐targeted micron‐sized particles of iron oxide as MRI contrast agent for detection of vascular remodeling after cerebral ischemia

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