The Pharmacology of Human Blood Vessels in vivo

1995 ◽  
Vol 32 (1) ◽  
pp. 2-15 ◽  
Author(s):  
David J. Webb
Keyword(s):  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yohei Tsukada ◽  
Fumitaka Muramatsu ◽  
Yumiko Hayashi ◽  
Chiaki Inagaki ◽  
Hang Su ◽  
...  

AbstractAngiogenesis contributes to numerous pathological conditions. Understanding the molecular mechanisms of angiogenesis will offer new therapeutic opportunities. Several experimental in vivo models that better represent the pathological conditions have been generated for this purpose in mice, but it is difficult to translate results from mouse to human blood vessels. To understand human vascular biology and translate findings into human research, we need human blood vessel models to replicate human vascular physiology. Here, we show that human tumor tissue transplantation into a cranial window enables engraftment of human blood vessels in mice. An in vivo imaging technique using two-photon microscopy allows continuous observation of human blood vessels until at least 49 days after tumor transplantation. These human blood vessels make connections with mouse blood vessels as shown by the finding that lectin injected into the mouse tail vein reaches the human blood vessels. Finally, this model revealed that formation and/or maintenance of human blood vessels depends on VEGFR2 signaling. This approach represents a useful tool to study molecular mechanisms of human blood vessel formation and to test effects of drugs that target human blood vessels in vivo to show proof of concept in a preclinical model.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Tomasz Brzoska ◽  
Tomasz W. Kaminski ◽  
Ravi Vats ◽  
Egemen Tutuncuoglu ◽  
Mark T Gladwin ◽  
...  

Pulmonary thrombosis is a major complication associated with high morbidity. Despite advances in diagnosis and treatment, the pathophysiology of pulmonary thrombosis remains incompletely understood. New clinical evidence suggests that in situ platelet activation resulting in enhanced procoagulant activity may promote pulmonary thrombosis. Improved understanding of the etiological mechanism would enable the development of new therapies for pulmonary thrombosis. Collagen and thromboplastin (TF) were administered intravascularly (IV) to C57BL/6 (WT) mice and the pulmonary microcirculation was visualized using quantitative fluorescence intravital fluorescence lung microscopy (qFILM). Fluorochrome-conjugated anti-mouse CD49b Ab and dextran was administered IV for in vivo staining of circulating platelets and visualization of blood vessels, respectively. Pulmonary thrombosis was defined as occlusion of blood vessels with platelet aggregates leading to pulmonary ischemia. Additionally, quantitative microfluidic fluorescence microscopy (qMFM) was used to study the effect of platelet αIIbβ3 inhibition on platelet procoagulant activity in human blood under vascular mimetic flow conditions. Collagen and TF triggered dose-dependent pulmonary thrombosis in mice in vivo, which involved development of platelet-rich thrombi in the pulmonary arteriolar bottlenecks (junction of pulmonary arteriole and capillaries), resulting in a transient ischemia in the arteriole and the down-stream capillary tree. The pulmonary arteriole thrombosis triggered by IV collagen or TF was protracted, lethal and completely abrogated following IV administration of αIIbβ3 receptor inhibitor (eptifibatide). Inhibition of platelet αIIbβ3 also significantly reduced platelet procoagulant activity, fibrin formation and thrombus formation in human blood flowing through microfluidic channels ex vivo. Our current findings suggest that αIIbβ3-dependent platelet procoagulant activity promotes pulmonary thrombosis. Both our models have potential application in investigating the molecular determinants of pulmonary thrombosis in diverse pulmonary disorders as well as evaluating efficacy of new antithrombotic drugs. Disclosures No relevant conflicts of interest to declare.


Wound Healing ◽  
2003 ◽  
pp. 161-178
Author(s):  
Peter J. Polverini ◽  
Jacques E. Nör ◽  
Martin C. Peters ◽  
David J. Mooney

2018 ◽  
Vol 113 (25) ◽  
pp. 253702 ◽  
Author(s):  
Zhu Zheng ◽  
Lin Huang ◽  
Huabei Jiang

1962 ◽  
Vol 08 (01) ◽  
pp. 096-100
Author(s):  
Marvin Murray ◽  
Robert Johnson

Summary133 blood vessels were evaluated for vasculokinase concentration in the freshly morbid state. High concentrations of activity were found in the aorta, iliac artery, superior mesenteric artery and popliteal artery. Activity was occasionally found in the inferior vena cava and common iliacs veins. Other vessels evaluated had no activity. Evaluation of the data with respect to vas-culokinase activity and atherosclerosis suggests higher levels of vasculokinase in those vessels having atherosclerosis.


Circulation ◽  
1995 ◽  
Vol 92 (7) ◽  
pp. 1876-1882 ◽  
Author(s):  
Alexander Mülsch ◽  
Peter Mordvintcev ◽  
Eberhard Bassenge ◽  
Frank Jung ◽  
Bernd Clement ◽  
...  

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 192-198 ◽  
Author(s):  
Lorenzo Tarli ◽  
Enrica Balza ◽  
Francesca Viti ◽  
Laura Borsi ◽  
Patrizia Castellani ◽  
...  

Angiogenesis is a characteristic feature of many aggressive tumors and of other relevant disorders. Molecules capable of specifically binding to new-forming blood vessels, but not to mature vessels, could be used as selective vehicles and would, therefore, open diagnostic and therapeutic opportunities. We have studied the distribution of the ED-B oncofetal domain of fibronectin, a marker of angiogenesis, in four different tumor animal models: the F9 murine teratocarcinoma, SKMEL-28 human melanoma, N592 human small cell lung carcinoma, and C51 human colon carcinoma. In all of these experimental models we observed accumulation of the fibronectin isoform containing the ED-B domain around neovascular structures when the tumors were in the exponentially growing phase, but not in the slow-growing phase. Then we performed biodistribution studies in mice bearing a subcutaneously implanted F9 murine teratocarcinoma, using a high-affinity human antibody fragment (L19) directed against the ED-B domain of fibronectin. Radiolabeled L19, but not an irrelevant anti-lysozyme antibody fragment (D1.3), efficiently localizes in the tumoral vessels. The maximal dose of L19 accumulated in the tumor was observed 3 hours after injection (8.2% injected dose per gram). By virtue of the rapid clearance of the antibody fragment from the circulation, tumor-to-blood ratios of 1.9, 3.7, and 11.8 were obtained at 3, 5, and 24 hours, respectively. The tumor-targeting performance of L19 was not dose-dependent in the 0.7 to 10 μg range of injected antibody. The integral of the radioactivity localized in tumoral vessels over 24 hours was greater than 70-fold higher than the integral of the radioactivity in blood over the same time period, normalized per gram of tissue or fluid. These findings quantitatively show that new-forming blood vessels can selectively be targeted in vivo using specific antibodies, and suggest that L19 may be of clinical utility for the immunoscintigraphic detection of angiogenesis in patients.


2019 ◽  
Vol 12 (06) ◽  
pp. 1950012 ◽  
Author(s):  
Hequn Zhang ◽  
Weisi Xie ◽  
Ming Chen ◽  
Liang Zhu ◽  
Zhe Feng ◽  
...  

Rodents are popular biological models for physiological and behavioral research in neuroscience and rats are better models than mice due to their higher genome similarity to human and more accessible surgical procedures. However, rat brain is larger than mice brain and it needs powerful imaging tools to implement better penetration against the scattering of the thicker brain tissue. Three-photon fluorescence microscopy (3PFM) combined with near-infrared (NIR) excitation has great potentials for brain circuits imaging because of its abilities of anti-scattering, deep-tissue imaging, and high signal-to-noise ratio (SNR). In this work, a type of AIE luminogen with red fluorescence was synthesized and encapsulated with Pluronic F-127 to make up form nanoparticles (NPs). Bright DCDPP-2TPA NPs were employed for in vivo three-photon fluorescent laser scanning microscopy of blood vessels in rats brain under 1550[Formula: see text]nm femtosecond laser excitation. A fine three-dimensional (3D) reconstruction up to the deepness of 600[Formula: see text][Formula: see text]m was achieved and the blood flow velocity of a selected vessel was measured in vivo as well. Our 3PFM deep brain imaging method simultaneously recorded the morphology and function of the brain blood vessels in vivo in the rat model. Using this angiography combined with the arsenal of rodent’s brain disease, models can accelerate the neuroscience research and clinical diagnosis of brain disease in the future.


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