Dysregulation of RNF213 promotes cerebral hypoperfusion

Abstract

RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF.

Current-Voltage Characteristic and Shot Noise of Shift Current Photovoltaics

“…We study a system in an external electric field by using Keldysh Green's function and gradient expansion. In the presence of an external electric field E, the Green's function and the self energy are expanded with respect to E as [16][17][18]…”

“…We study a system in an external electric field by using gauge invariant formulation of Keldysh Green's function and its gradient expansion. In the presence of an external dc electric field E dc , the Green's function is expanded [16][17][18]. In addition, we employ Floquet two band model to incorporate ac electric field E light of constant light that is irradiated to the sample and produces shift current [8].…”

Scaling theory of a quantum ratchet

“…Neglecting the spin degrees of freedom, ε n (k) is symmetric between k and −k, i.e., ε n (k) = ε n (−k) as far as V (x) is real, i.e., Hermitian. Therefore, the transport phenomena are symmetric between right and left directions as long as the many-body interaction is neglected [9]. This is in sharp contrast to the daily experience, which is governed by classical mechanics, that it is more difficult to climb up the steeper slope compared with the gentle one.…”

Distribution of Intracranial Major Artery Stenosis/Occlusion According to RNF213 Polymorphisms

“…Although RNF213 variants have been associated with various vascular disorders, the mechanisms through which they contribute to these disorders are unknown [17]. Experimental reports have suggested multiple pathogenic mechanisms involving endothelial function, smooth muscle cell proliferation, inflammatory signaling pathways, hemostasis, angiogenesis, vascular remodeling, and response to hypoxia [7,9,10,[18][19][20][21][22]. However, an RNF213-deficient mouse model did not exhibit any vascular abnormality [23].…”

“…Really interesting new gene (RING) 2 of 12 finger protein 213 (RNF213) is encoded by the RNF213 gene (DDBJ/EMBL/GenBank accession number AB537889) on chromosome 17q25, which has received considerable attention as a susceptibility gene for MMD and ICASO in Asians [4][5][6]. The functional role of RNF213 on cerebral vasculature has not been established, but experimental studies have suggested that it affects cerebral blood perfusion, angiogenesis, and oxygen consumption [7][8][9][10].…”