Toshio Higashi

Simultaneous induction of the four subunits of the TRAP complex by ER stress accelerates ER degradation

The mammalian translocon‐associated protein (TRAP) complex comprises four transmembrane protein subunits in the endoplasmic reticulum. The complex associates with the Sec61 translocon, although its function in vivo remains unknown. Here, we show the involvement of the TRAP complex in endoplasmic reticulum‐associated degradation (ERAD). All four subunits are induced simultaneously by endoplasmic reticulum stresses from the X‐box‐binding protein 1/inositol‐requiring 1α pathway. RNA interference knockdown of each subunit causes disruption of the native complex and significant delay in the degradation of various ERAD substrates, including the α1‐antitrypsin null Hong Kong variant (NHK). In a pulse‐chase experiment, the TRAP complex associated with NHK at a late stage, indicating its involvement in the ERAD pathway rather than in biosynthesis of nascent polypeptides in the endoplasmic reticulum. In addition, the TRAP complex bound preferentially to misfolded proteins rather than correctly folded wild‐type substrates. Thus, the TRAP complex induced by the unfolded protein response pathway might discriminate ERAD substrates from correctly folded substrates, accelerating degradation.

Near-infrared spectroscopy in carotid artery stenting predicts cerebral hyperperfusion syndrome

Objective: Cerebral hyperperfusion syndrome (CHS) following carotid artery stenting (CAS) or carotid endarterectomy (CEA) is rare but often fatal once intracranial hemorrhage has occurred. In particular, CHS occurs significantly earlier after CAS than after CEA. Thus a monitoring method for early detection of CHS is required. Near-infrared spectroscopy (NIRS) provides a noninvasive monitoring technique for assessing regional cerebral oxygen saturation (rSO2). This study evaluated the usefulness of transcranial NIRS during CAS for prediction of CHS. Methods: Periprocedural rSO2 was monitored in 64 cases of CAS (52 men, 12 women; 71 ± 6.6 years). The average degree of carotid stenosis was 76.8 ± 11.3% by North American Symptomatic Carotid Endarterectomy Trial criteria. Bifrontal rSO2 was monitored during the procedure using NIRS. Seventeen patients were symptomatic and 47 were asymptomatic. CHS was diagnosed by increased cerebral blood flow by SPECT performed on the day after treatment with deterioration of neurologic symptoms. Results: CHS was observed in two cases (3.1%). In the CHS group, post-reperfusion rSO2 values increased >24% from baseline until 3 minutes after reperfusion. In the non-CHS group, the normal upper limit (NUL) of the rSO2 change was set at 10.0% at 3 minutes after reperfusion. In the CHS group, rSO2 at 3 minutes after reperfusion was markedly higher than the NUL. In patients showing an rSO2 at 3 minutes after reperfusion increased by more than 10.0%, CHS following CAS could be predicted. Conclusion: Periprocedural increases in regional cerebral oxygen saturation measured by near- infrared spectroscopy can be an excellent predictor of cerebral hyperperfusion syndrome after carotid artery stenting.

Intraoperative stenting for brachiocephalic and carotid artery stenosis.

OBJECTIVEEndovascular stenting is an alternative treatment for brachiocephalic artery stenosis, replacing standard surgical approaches such as carotid endarterectomy. However, a percutaneous approach may be difficult because various conditions such as severe arteriosclerosis of iliac or femoral arteries and aortic disease. We report our experience with intraoperative stenting for these lesions, presenting indications, strategy, and results. METHODSSeven patients underwent intraoperative stent placement via an open cervical approach. The sites of lesions included 1 innominate artery, 1 common carotid artery, and 5 cervical carotid arteries. Stenting was performed with a sheath introducer placed through a surgically exposed common carotid artery via a small skin incision or common carotid artery exposed for simultaneously performed carotid endarterectomy. Distal protection was used in 6 patients with an endovascular protective balloon or external clamping with forceps. RESULTSSufficient dilation of stenosis was obtained in all cases. No complications such as transient ischemic attack, cerebral infarction, and hyperperfusion were encountered. Wound hematoma was not experienced despite perioperative antiplatelet therapy and heparinization during the procedure. Angiographic follow-up over 1 year showed no restenosis in 5 available patients. CONCLUSIONIntraoperative stenting may be an excellent alternative for patients in whom both direct surgical approach and standard percutaneous endovascular approach are not possible.

Fibro-fatty volume of culprit lesions in Virtual Histology intravascular ultrasound is associated with the amount of debris during carotid artery stenting.

Objectives: This study aimed to evaluate the relationship between the amount of aspirated debris during distal balloon-protected carotid artery stenting (CAS) and the pre-intervention plaque composition, as assessed by Virtual Histology™ (VH) intravascular ultrasound (IVUS). Methods: The study subjects were 25 consecutive patients (mean age, 73.0 ± 5.2 years; 20 males and 5 females) who underwent CAS under distal balloon protection. The average rate of carotid stenosis was 74.6 ± 12.9% by North American Symptomatic Carotid Endarterectomy Trial criteria. We assessed culprit plaque components by VH-IVUS before CAS. Aspirated debris was filtered, stained with HE and mounted onto glass slides. The quantity of debris was evaluated by measuring its surface area. We evaluated the relationship between the quantity of aspirated debris and VH-IVUS measurements before CAS. Results: The amount of debris during CAS was positively correlated with the total plaque volume in grayscale IVUS (Rs = 0.480, p = 0.015) and fibro-fatty volumes over the entire lesion length in VH-IVUS (Rs = 0.561, p = 0.001). Conclusions: Culprit lesions with large plaque volumes, especially larger fibro-fatty volumes, as imaged by VH-IVUS, are associated with large amounts of debris during balloon-protected CAS.

Angioplasty and stent deployment in acute sinus thrombosis following endovascular treatment of dural arteriovenous fistulae

We report on the successful treatment of acute sinus thrombosis associated with endovascular treatment of intracranial dural arteriovenous fistulae (DAVF) by sinus angioplasty with stent deployment. A 76-year-old man presented with intracerebral hemorrhage, Cognard type IIa+b DAVF of the left sigmoid sinus, and type IIa DAVF of the torcular herophili. During transvenous sinus embolization, acute thrombosis of the stenotic lesion in the left transverse sinus occurred. The thrombosis caused isolated sinus and cortical venous reflux (CVR). The patient was treated by stent-supported sinus angioplasty, which led to an immediate improvement of the sinus thrombosis and associated CVR.