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RISS 인기검색어
- 검색키워드
- 저자 : David L. Penn (검색결과 2 건)
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Katie Pricola Fehnel,David L. Penn,Micah Duggins-Warf,Maxwell Gruber,Steven Pineda,Julie Sesen,Alexander Moses-Gardner,Nishali Shah,Jessica Driscoll,David Zurakowski,Darren B. Orbach,Edward R. Smith 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
We investigated (1) EphrinB2 and EphB4 receptor expression in cerebral AVMs, (2) the impact of an altered EphrinB2: EphB4 ratio on brain endothelial cell function and (3) potential translational applications of these data. The following parameters were compared between AVM endothelial cells (AVMECs) and human brain microvascular endothelial cells (HBMVECs): quantified EphrinB2 and EphB4 expression, angiogenic potential, and responses to manipulation of the EphrinB2:EphB4 ratio via pharmacologic stimulation/inhibition. To investigate the clinical relevance of these in vitro data, Ephrin expression was assessed in AVM tissue (by immunohistochemistry) and urine (by ELISA) from pediatric patients with AVM (n=30), other cerebrovascular disease (n=14) and control patients (n=29), and the data were subjected to univariate and multivariate statistical analyses. Compared to HBMVECs, AVMECs demonstrated increased invasion (p=0.04) and migration (p=0.08), impaired tube formation (p=0.06) and increased EphrinB2:EphB4 ratios. Altering the EphrinB2:EphB4 ratio (by increasing EphrinB2 or blocking EphB4) in HBMVECs increased invasion (p=0.03 and p<0.05, respectively). EphrinB2 expression was increased in AVM tissue, which correlated with increased urinary EphrinB2 levels in AVM patients. Using the optimal urinary cutoff value (EphrinB2>25.7pg/μg), AVMs were detected with high accuracy (80% vs. controls) and were distinguished from other cerebrovascular disease (75% accuracy). Posttreatment urinary EphrinB2 levels normalized in an index patient. In summary, AVMECs have an EphrinB2:EphB4 ratio that is increased compared to that of normal HBMVECs. Changing this ratio in HBMVECs induces AVMEC-like behavior. EphrinB2 is clinically relevant, and its levels are increased in AVM tissue and patient urine. This work suggests that dysregulation of the EphrinB2:EphB4 signaling cascade and increases in EphrinB2 may play a role in AVM development, with potential utility as a diagnostic and therapeutic target.
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Hemodynamic Impact of a Spontaneous Cervical Dissection on an Ipsilateral Saccular Aneurysm
Alfred P. See,Bradley A. Gross,David L. Penn,Rose Du,Kai U Frerichs 대한뇌혈관외과학회 2016 Journal of Cerebrovascular and Endovascular Neuros Vol.18 No.2
The dynamic, hemodynamic impact of a cervical dissection on an ipsilateral, intracranial saccular aneurysm has not been well illustrated. This 45-year-old female was found to have a small, supraclinoid aneurysm ipsilateral to a spontaneous cervical internal carotid artery dissection. With healing of the dissection, the aneurysm appeared to have significantly enlarged. Retrospective review of the magnetic resonance imaging (MRI) at the time of the initial dissection demonstrated thrombus, similar in overall morphology to the angiographic appearance of the "enlarged" aneurysm. As the dissection healed far proximal to the intradural portion of the internal carotid artery, this suggested that the aneurysm was likely a typical, saccular posterior communicating artery aneurysm that had thrombosed and then recanalized secondary to flow changes from the dissection. The aneurysm was coiled uneventfully, in distinction from more complex treatment approaches such as flow diversion or proximal occlusion to treat an enlarging, dissecting pseudoaneurysm. This case illustrates that flow changes from cervical dissections may result in thrombosis of downstream saccular aneurysms. With healing, these aneurysms may recanalize and be misidentified as enlarging dissecting pseudoaneurysms. Review of an MRI from the time of the dissection facilitated the conclusion that the aneurysm was a saccular posterior communicating artery aneurysm, influencing treatment approach.
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