Pulmonary arterio-venous malformation.
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ABSTRACT:
SUBMITTER: Sahoo J
PROVIDER: S-EPMC8257201 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Pulmonary arterio-venous malformation.
Sahoo Jyotirmaya J Patnaik Uttam Kumar UK
The Indian journal of medical research 20201101 Suppl 1
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Project description:Objectives: We have previously identified a population of cells that expressed stemness-associated markers in extracranial arterio-venous malformation (AVM) and demonstrated expression of cathepsins B, D, and G on embryonic stem cell (ESC)-like populations in other vascular anomalies. This study investigated the expression of cathepsins B, D, and G, and their localization in relation to this primitive population in extracranial AVM. Methods: Immunohistochemical staining was performed on AVM tissue samples from 13 patients to demonstrate expression of cathepsins B, D, and G. Western blotting was performed on four AVM tissue samples and three AVM-derived primary cell lines to confirm protein expression of cathepsins B and D proteins. RT-qPCR was performed on three AVM-derived primary cell lines to demonstrate transcript expression of cathepsins B, D, and G. Enzymatic activity assays were performed on three AVM-derived primary cell lines to investigate if cathepsins B and D were active. Localization of the cathepsins was investigated using immunofluorescence dual-staining of the cathepsins with the ESC markers OCT4 and SOX2, and mast cells marker chymase on two of the 13 AVM tissue samples. Results: Immunohistochemical staining demonstrated expression of cathepsins B, D, and G in all 13 AVM tissue samples. Western blotting showed expression of cathepsins B and D proteins in all four AVM tissue samples and all three AVM-derived primary cell lines. RT-qPCR demonstrated transcripts of cathepsins B, D, and G in all three AVM-derived primary cell lines. Enzymatic activity assays showed that cathepsins B and D were active. Immunofluorescence staining showed expression of cathepsins B and D on the OCT4+/SOX2+ endothelium and media of the lesional vessels and cells within the stroma in AVM nidus. Cathepsin G was expressed on the chymase+ phenotypic mast cells. Conclusions: This study demonstrated the novel finding of the expression of cathepsins B, D, and G in AVM. Cathepsins B and D were expressed by the primitive population, and cathepsin G was localized to mast cells, within the AVM nidus.
| S-EPMC8367294 | biostudies-literature
Project description:Pulmonary arterio-venous fistula (PAVF) is an uncommon cause of cyanosis and should be suspected when normal cardiac examination is associated without evidence of intra-cardiac shunt. Off-label use of occluder devices in the catheter laboratories can be helpful and safe when chosen according to the morphology, site, and the size of the fistula, and it is considered a good alternative to surgery as it selectively occludes the PAVF while preserving the normal pulmonary vessels. Our case was a young boy accidentally discovered and diagnosed as having huge PAVF, after false diagnosis of coronavirus disease 2019. The fistula was successfully closed using septal occluder device which is not common to use such device in such lesion. Follow up with computed tomography pulmonary angiogram confirmed the closure results with good device position and no residual shunt.Learning objectives1To encourage the use of simple non-invasive tools like pulse oximeter that can help in the diagnosis of clinically un-discovered de-saturated patients.2To be malleable with the different occluder devices and be able to use any, according to the lesion you have to close not only those that they were designed for.
| S-EPMC9169007 | biostudies-literature
Project description:BackgroundCerebral arterio venous malformations (AVM) are a major causal factor for intracranial hemorrhage, which result in permanent disability or death. The molecular mechanisms of AVM are complex, and their pathogenesis remains an enigma. Current research on cerebral AVM is focused on characterizing the molecular features of AVM nidus to elucidate the aberrant signaling pathways. The initial stimuli that lead to the development of AVM nidus structures between a dilated artery and a vein are however not known.MethodsIn order to understand the molecular basis of development of cerebral AVM, we used in-depth RNA sequencing with the total RNA isolated from cerebral AVM nidus. Immunoblot and qRT-PCR assays were used to study the differential gene expression in AVM nidus, and immunofluorescence staining was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues. Immunohistochemistry was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues.ResultsThe transcriptome study has identified 38 differentially expressed genes in cerebral AVM nidus, of which 35 genes were upregulated and 3 genes were downregulated. A final modular analysis identified an upregulation of ALDH1A2, a key rate-limiting enzyme of retinoic acid signaling pathway. Further analysis revealed that CYR61, a regulator of angiogenesis, and the target gene for retinoic acid signaling is upregulated in AVM nidus. We observed that astrocytes associated with AVM nidus are abnormal with increased expression of GFAP and Vimentin. Triple immunofluorescence staining of the AVM nidus revealed that CYR61 was also overexpressed in the abnormal astrocytes associated with AVM tissue.ConclusionUsing high-throughput RNA sequencing analysis and immunostaining, we report deregulated expression of retinoic acid signaling genes in AVM nidus and its associated astrocytes and speculate that this might trigger the abnormal angiogenesis and the development of cerebral AVM in humans.
| S-EPMC7923665 | biostudies-literature
Project description:Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal dominant disorder associated with mutations in the bone morphogenetic protein (BMP) pathway. Inherited heterozygous loss of function mutations and acquired loss of heterozygosity in either Alk1, Eng, or Smad4 lead to the development of arteriovenous malformations (AVMs), which trigger local vessel instability, hypoxia and vessel leakage or rupture. Current models assume common cellular pathomechanisms culminating in altered endothelial cell (EC) shape regulation, directional migration and proliferation control as a consequence of deficient BMP pathway signaling in ECs under the influence of blood-flow mediated shear stress. Here we report that loss of Alk1 or Smad4 surprisingly triggers very distinct endothelial phenotypes, signaling dynamics and transcriptional changes in ECs, both in vitro and in vivo. EC behavior in both in vivo and mosaic flow cultures illustrate that cells deficient in Smad4 effectively migrate against the direction of fluid shear, from veins to arteries, whereas cells lacking Alk1 fail to polarize and migrate against flow. Our data suggest that AVMs triggered by Smad4 mutations occur through hyperpruning of capillaries, thus precipitating flow in a single shunt, whereas AVMs caused by Alk1 mutation grow by cell accumulations close to the vein, as well as the persistence of a hyperdense plexus that drives nidus formation. We propose that the cellular pathomechanisms leading to AVM formation are not the same if the upstream BMP receptor Alk1, or the downstream common transcription factor Smad4 are mutated, raising the prospect for urgently needed, mechanism-based, therapeutic avenues that need to be tailored to correcting the specific pathomechanism.
2025-02-18 | GSE282952 | GEO
Project description:Arterial-venous malformations (AVMs) are direct connections between arteries and veins without an intervening capillary bed. Either familial inherited or sporadically occurring, localized pericytes (PCs) drop is among the AVMs' hallmarks. Whether impaired PC coverage triggers AVMs or it is a secondary event is unclear. Here we evaluated the role of the master regulator of PC recruitment, Platelet derived growth factor B (PDGFB) in AVM pathogenesis. Using tamoxifen-inducible deletion of Pdgfb in endothelial cells (ECs), we show that disruption of EC Pdgfb-mediated PC recruitment and maintenance leads to capillary enlargement and organotypic AVM-like structures. These vascular lesions contain non-proliferative hyperplastic, hypertrophic and miss-oriented capillary ECs with an altered capillary EC fate identity. Mechanistically, we propose that PDGFB maintains capillary EC size and caliber to limit hemodynamic changes, thus restricting expression of Krüppel like factor 4 and activation of Bone morphogenic protein, Transforming growth factor β and NOTCH signaling in ECs. Furthermore, our study emphasizes that inducing or activating PDGFB signaling may be a viable therapeutic approach for treating vascular malformations.
| S-EPMC11021264 | biostudies-literature
Project description:Pulmonary arterio-venous fistula is an uncommon cause of cyanosis and should be suspected when normal cardiac examination is associated without evidence of intra-cardiac shunt. Diagnosis of extra-cardiac shunt can be suspected by contrast echocardiography using agitated saline and confirmation of pulmonary arterio-venous fistula can be made by computed tomography pulmonary angiography with information regarding the size feeding vessels necessary for the planning of intervention. With the advancement of trans-catheter devices, fistula can be occluded successfully by embolotherapy. Coils, duct occluders, and vascular plugs are some of the commonly used trans-catheter devices among the armamentarium. Each device has its own inherent advantages and limitations. However, operators' familiarity and expertise is an important parameter to choose the device to be employed in closure of fistula. The experience of Amplatzer family of devices in closure of pulmonary arterio-venous fistula is limited in the literature. We report a case of large pulmonary arterio-venous fistula successfully closed with a 20 mm Amplatzer septal occluder device in a 16-year-old cyanotic boy. Post-procedure contrast echocardiography confirmed absence of right to left shunt and computed tomography pulmonary angiography confirmed the device in situ closing the feeding vessel. Over a follow-up of six months reversal of clubbing and cyanosis was noted. <Learning objective: Patients with cyanosis with normal cardiac examination without evident intra-cardiac shunt in echocardiography should be evaluated for pulmonary arterio-venous fistula. Computed tomography Pulmonary angiography is gold standard but contrast echocardiography can be valuable. Percutaneous trans-catheter closure using coils, duct occluders, or vascular plugs can be an alternative to surgery. Choice of device depends on size and tortuosity of the feeding vessel as well as operator's familiarity with the device.>.
| S-EPMC7283301 | biostudies-literature
Project description:IntroductionThe fetoplacental vasculature network is essential for the exchange of nutrients, gases and wastes with the maternal circulation and for normal fetal development. The present study quantitatively compares arterial and venous morphological and functional differences in the mouse fetoplacental vascular network.MethodsHigh resolution X-ray micro-computed tomography was used to visualize the 3D geometry of the arterial and venous fetoplacental vasculature in embryonic day 15.5 CD-1 mice (n = 5). Automated image analysis was used to measure the vascular geometry of the approximately 4100 arterial segments and 3200 venous segments per specimen to simulate blood flow through these networks.ResultsBoth the arterial and venous trees demonstrated a hierarchical branching structure with 8 or 9 (arterial) or 8 (venous) orders. The venous tree was smaller in volume and overall dimensions than the arterial tree. Venous vessel diameters increased more rapidly than arteries with each successive order, leading to lower overall resistance, although the umbilical vein was notably smaller and of higher resistance than these scaling relationships would predict. Simulation of blood flow for these vascular networks showed that 57% of total resistance resides in the umbilical artery and arterial tree, 17% in the capillary bed, and 26% in the venous tree and umbilical vein.DiscussionA detailed examination of the mouse fetoplacental arterial and venous tree revealed features, such as the distribution of resistance and the dimension of the venous tree, that were both morphologically distinct from other vascular beds and that appeared adapted to the specialized requirements of sustaining a fetus.
| S-EPMC5679460 | biostudies-literature
Project description: Not available
| S-EPMC10281625 | biostudies-literature
Project description:Hereditary hemorrhagic telangiectasia is a rare autosomal dominant vascular disease defined by the presence of mucosal and cutaneous telangiectasia and visceral arterio-venous malformations. The latter are abnormal capillary-free direct communications between the pulmonary and systemic circulations with the following consequences: arterial hypoxemia caused by right-to-left shunts; paradoxical embolism with transient ischemic attack or stroke and brain abscess caused by the absence of the normally filtering capillary bed; and hemoptysis or hemothorax due to the rupture of the thin-walled arterio-venous malformations (particularly during pregnancy). It is frequently underdiagnosed, commonly presenting as complications from shunting through arterio-venous malformations: dyspnea, chronic bleeding, or embolism. Arterio-venous malformations are present not only in the lungs, but can also be found in the liver, central nervous system (mainly in the brain), nasal mucosa, or the gastrointestinal tract. The first choice of therapy is embolization of the afferent arteries of the arterio-venous malformations, a minimally invasive procedure with a high efficacy, a low morbidity, and low mortality. Other therapeutic modalities are surgery (resection) or stereotactic radiosurgery (using radiation). Routine screening for arterio-venous malformations is indicated in patients diagnosed with this condition and can prevent severe complications such as acute hemorrhages, brain abscesses, or strokes. Clinicians should provide a long-term follow-up for patients with arterio-venous malformations, in an effort to detect their growth or reperfusion in case of previously treated malformations. In spite of two experts' consensuses, it still possesses multiple therapeutic challenges for physicians, as several aspects regarding the screening and management of arterio-venous malformations still remain controversial. Multidisciplinary teams are especially useful in complex cases.
| S-EPMC9105924 | biostudies-literature
Project description:Recent reports suggest that mammalian embryonic coronary endothelium (CoE) originates from the sinus venosus and ventricular endocardium. However, the contribution of extracardiac cells to CoE is thought to be minor and nonsignificant for coronary formation. Using classic (Wt1(Cre)) and previously undescribed (G2-Gata4(Cre)) transgenic mouse models for the study of coronary vascular development, we show that extracardiac septum transversum/proepicardium (ST/PE)-derived endothelial cells are required for the formation of ventricular coronary arterio-venous vascular connections. Our results indicate that at least 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE compartment. Moreover, we show that conditional deletion of the ST/PE lineage-specific Wilms' tumor suppressor gene (Wt1) in the ST/PE of G2-Gata4(Cre) mice and in the endothelium of Tie2(Cre) mice disrupts embryonic coronary transmural patterning, leading to embryonic death. Taken together, our results demonstrate that ST/PE-derived endothelial cells contribute significantly to and are required for proper coronary vascular morphogenesis.
| S-EPMC4725486 | biostudies-literature