A comprehensive approach to visual and functional assessment of experimental vascular lesions in vivo

2004 ◽  
Vol 286 (6) ◽  
pp. H2461-H2467 ◽  
Author(s):  
Rainer Wessely ◽  
Makarios Paschalidis ◽  
Stefan Wagenpfeil ◽  
Franziska Wegener ◽  
Franz-Josef Neumann ◽  
...  
Keyword(s):  
Time Course ◽  
Interobserver Variability ◽  
Neointimal Hyperplasia ◽  
Duplex Sonography ◽  
Vascular Lesions ◽  
Therapeutic Approaches ◽  
Lesion Development ◽  
Injury Model ◽  
Carotid Injury

The rat carotid injury model is the most widely used model to study the pathophysiology of neointimal hyperplasia as well as the value of novel therapeutic approaches to limit vasoproliferative diseases such as restenosis. For lesion assessment, the current gold standard of histomorphometry neither provides integral insight into the vascular lesion in vivo nor assesses of functional lesion-associated flow alterations and the time course of lesion development. To overcome these limitations, we applied and validated duplex sonography as a novel tool for comprehensive lesions assessment in vivo. Left rat common carotid arteries (CCA) were balloon injured. Duplex sonography was performed in both injured and noninjured CCAs before and up to 14 days postinjury. Sham-operated animals served as controls. The parameters determined were vessel lumen diameter as well as systolic and end-diastolic flow velocity, time-dependent lesion development, and intra- and interobserver variability. Subsequently, the model was applied to validate the therapeutic effect of gene transfer into the vessel wall and compared with histomorphometry. We show that duplex sonography in the experimental carotid injury model allows accurate follow-up of lesion development in vivo with low intra- and interobserver variability. It can be easily adopted to assess the efficacy of therapeutic approaches even with limited technical experience and adds valuable functional data to mere postmortem histomorphometric analysis, thereby closing the gap between experimental approaches and clinical importance of vascular lesions.

The Inhibition of Neointimal Hyperplasia by Combination of External Radiation and Paclitaxel in A Rat Carotid Injury Model

2000 ◽  
Vol 30 (6) ◽  
pp. 758
Author(s):  
Ki Yuk Chang ◽  
Ki Bae Seung ◽  
Dong Heon Kang ◽  
Sang Hyun Ihm ◽  
Hae Ok Jung ◽  
...  
Keyword(s):  
Neointimal Hyperplasia ◽  
External Radiation ◽  
Injury Model ◽  
Carotid Injury

scholarly journals Platelet-Derived Extracellular Vesicles Increase Col8a1 Secretion and Vascular Stiffness in Intimal Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Han Bao ◽  
Zi-Tong Li ◽  
Lei-Han Xu ◽  
Tong-Yue Su ◽  
Yue Han ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Extracellular Vesicles ◽  
Neointimal Hyperplasia ◽  
Vascular Stiffness ◽  
Akt Pathway ◽  
Activated Platelets ◽  
Injury Model ◽  
Intimal Injury

The arterial mechanical microenvironment, including stiffness, is a crucial pathophysiological feature of vascular remodeling, such as neointimal hyperplasia after carotid endarterectomy and balloon dilatation surgeries. In this study, we examined changes in neointimal stiffness in a Sprague-Dawley rat carotid artery intimal injury model and revealed that extracellular matrix (ECM) secretion and vascular stiffness were increased. Once the endothelial layer is damaged in vivo, activated platelets adhere to the intima and may secrete platelet-derived extracellular vesicles (pEVs) and communicate with vascular smooth muscle cells (VSMCs). In vitro, pEVs stimulated VSMCs to promote collagen secretion and cell adhesion. MRNA sequencing analysis of a carotid artery intimal injury model showed that ECM factors, including col8a1, col8a2, col12a1, and elastin, were upregulated. Subsequently, ingenuity pathway analysis (IPA) was used to examine the possible signaling pathways involved in the formation of ECM, of which the Akt pathway played a central role. In vitro, pEVs activated Akt signaling through the PIP3 pathway and induced the production of Col8a1. MicroRNA (miR) sequencing of pEVs released from activated platelets revealed that 14 of the top 30 miRs in pEVs targeted PTEN, which could promote the activation of the Akt pathway. Further research showed that the most abundant miR targeting PTEN was miR-92a-3p, which promoted Col8a1 expression. Interestingly, knockdown of Col8a1 expression in vivo abrogated the increase in carotid artery stiffness and simultaneously increased the degree of neointimal hyperplasia. Our results revealed that pEVs may deliver miR-92a-3p to VSMCs to induce the production and secretion of Col8a1 via the PTEN/PIP3/Akt pathway, subsequently increasing vascular stiffness. Therefore, pEVs and key molecules may be potential therapeutic targets for treating neointimal hyperplasia.

Abstract 356: IFN-γ-Dependent TET2 Repression in Coronary Allograft Vasculopathy

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Allison Ostriker ◽  
Kristen Leslie ◽  
Kathleen Martin
Keyword(s):  
T Cell ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Neointimal Hyperplasia ◽  
Transplant Recipients ◽  
Mtor Inhibition ◽  
Allograft Vasculopathy ◽  
Ifn Γ

Coronary allograft vasculopathy (CAV) occurs in 50% of heart transplant recipients at 10 years after surgery. Allograft failure secondary to CAV accounts for 30% of deaths in transplant recipients. CAV is characterized by concentric neointimal hyperplasia (NIH) in the graft vasculature results in ischemic injury. T cell-derived INF-γ is a well-established driver of NIH in CAV. The molecular mechanisms engaged by IFN-γ in vascular smooth muscle cells (VSMCs) in CAV are not fully elucidated. Our group recently showed that TET methylcytosine dioxygenase 2 is a regulator of VSMC phenotype. We hypothesized, therefore, that IFN-γ modulates TET2 expression and/or function in VSMCs. We found, using a single minor histocompatibility mismatch aorta interposition graft model of CAV, that TET2 expression was decreased in vivo in the graft neointima as compared to in control tissue. Further, we found that IFN-y was sufficient to repress TET2 gene transcription in human VSMC in vitro, and this repression was not reversed by mTOR inhibition. We then sought to determine if repression of TET2 is sufficient to exacerbate neointimal hyperplasia in the aorta graft model. We found that NIH was exacerbated in aorta grafts from VSMC-specific, inducible, TET2 knockout (iKO) donors versus controls. Neither T cell recruitment, nor STAT1 activation, was increased in the iKO grafts versus controls; while time course analysis showed that neointimal cells were primarily recipient-derived, suggesting a non-cell autonomous mechanism. Western blot analysis of VSMCs stimulated with IFN-γ for 0-120 minutes suggested that, in addition to STAT1 activation, IFN-γ decreases β-catenin signaling. ChIP-PCR studies showed that STAT1, but not LEF1 (a β-catenin coactivator), occupancy increased at the TET2 promotor following INF-γ stimulation. Studies are ongoing to further elucidate the requirement for STAT1 and/or β-catenin in IFN-γ-dependent repression of TET2 in VSMCs and the non-autonomous role of TET2 on mediating NIH progression in CAV. Since IFN-y-dependent repression of TET2 is not reversed by rapamycin, elucidating this pathway represents an opportunity for developing complementary therapies to mTOR inhibition that may result in improved outcomes and fewer side effects.

Vascular trauma of the hand – a systematic review

VASA ◽  
2019 ◽  
Vol 48 (3) ◽  
pp. 205-215 ◽  
Author(s):  
Uwe Wahl ◽  
Ingmar Kaden ◽  
Andreas Köhler ◽  
Tobias Hirsch
Keyword(s):  
Duplex Sonography ◽  
Vascular Trauma ◽  
Vascular Lesions ◽  
Critical Limb Ischaemia ◽  
Limb Ischaemia ◽  
Limited Information ◽  
Endovascular Interventions ◽  
Provocation Tests ◽  
Objective Basis ◽  
Allen Test

Abstract. Hypothenar or thenar hammer syndrome (HHS) and hand-arm vibration syndrome (HAVS) are diseases caused by acute or chronic trauma to the upper extremities. Since both diseases are generally related to occupation and are recognised as occupational diseases in most countries, vascular physicians need to be able to distinguish between the two entities and differentiate them from other diagnoses. A total of 867 articles were identified as part of an Internet search on PubMed and in non-listed occupational journals. For the analysis we included 119 entries on HHS as well as 101 papers on HAVS. A professional history and a job analysis were key components when surveying the patient’s medical history. The Doppler-Allen test, duplex sonography and optical acral pulse oscillometry were suitable for finding an objective basis for the clinical tests. In the case of HHS, digital subtraction angiography was used to confirm the diagnosis and plan treatment. Radiological tomographic techniques provided very limited information distal to the wrist. The vascular component of HAVS proved to be strongly dependent on temperature and had to be differentiated from the various other causes of secondary Raynaud’s phenomenon. The disease was medicated with anticoagulants and vasoactive substances. If these were not effective, a bypass was performed in addition to various endovascular interventions, especially in the case of HHS. Despite the relatively large number of people exposed, trauma-induced circulatory disorders of the hands can be observed in a comparatively small number of cases. For the diagnosis of HHS, the morphological detection of vascular lesions through imaging is essential since the disorder can be accompanied by critical limb ischaemia, which may require bypass surgery. In the case of HAVS, vascular and sensoneurological pathologies must be objectified through provocation tests. The main therapeutic approach to HAVS is preventing exposure.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

Time Course Change of the Heat-generating Capability of Dextran Magnetite Complex (DM) in vivo.

2001 ◽  
Vol 17 (2) ◽  
pp. 85-91 ◽  
Author(s):  
MICHIHIDE MITSUMORI ◽  
TORU SHIBATA ◽  
YASUSHI NAGATA ◽  
MASAHIRO HIRAOKA ◽  
MASAKATSU HASEGAWA ◽  
...  
Keyword(s):  
Time Course

Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine

1985 ◽  
Vol 108 (4) ◽  
pp. 511-517 ◽  
Author(s):  
Nandalal Bagchi ◽  
Birdie Shivers ◽  
Thomas R. Brown
Keyword(s):  
Time Course ◽  
Period 2 ◽  
Iodotyrosine Deiodinase ◽  
Rate Of Hydrolysis ◽  
Underlying Mechanisms ◽  
Excess Iodide ◽  
Sites Of Action ◽  
Hydrolysis Of

Abstract. Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of Nal to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4C1 and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis. Our data are consistent with the hypothesis that excess iodide acutely inhibits thyroglobulin hydrolysis by increasing the resistance of thyroglobulin to proteolytic degradation through increased iodination and coupling.

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