[Clinical Effect of Surgical Reconstruction of Extracranial Vertebral Artery].

Objective To evaluate the effect of surgical reconstruction of extracranial vertebral artery and to summarize the experience. Methods The clinical data of 15 patients undergoing surgical reconstruction of extracranial vertebral artery from September 2018 to June 2022 were collected.The operation methods,operation duration,intraoperative blood loss,operation complications,and relief of symptoms were retrospectively analyzed. Results Eleven patients underwent vertebral artery (V1 segment) to common carotid artery transposition,two patients underwent endarterectomy of V1 segment,two patients underwent V3 segment to external carotid artery bypass or transposition.The operation duration,intraoperative blood loss,and blocking time of common carotid artery varied within 120-340 min,50-300 ml,and 12-25 min,with the medians of 240 min,100 ml,and 16 min,respectively.There was no cardiac accident,cerebral hyperperfusion syndrome,cerebral hemorrhage or lymphatic leakage during the perioperative period.One patient suffered from cerebral infarction and three patients suffered from incomplete Horner's syndrome after the operation.During the follow-up (4-45 months,median of 26 months),there was no anastomotic stenosis,new cerebral infarction or cerebral ischemia. Conclusion Surgical reconstruction of extracranial vertebral artery is safe and effective,and individualized reconstruction strategy should be adopted according to different conditions.

Ablation and Inhibition of the Immunoproteasome Catalytic Subunit LMP7 Attenuate Experimental Abdominal Aortic Aneurysm Formation in Mice.

Low-molecular mass protein 7 (LMP7) is a proteolytic subunit of the immunoproteasome that is involved in regulating inflammatory responses. However, the role of LMP7 in the pathogenesis of abdominal aortic aneurysm (AAA) remains unknown. In this study, ApoE knockout (KO) or LMP7/ApoE double KO (dKO) mice were infused with angiotensin II (Ang II, 1000 ng/kg per minute) for up to 28 d. We found that LMP7 expression was significantly upregulated in AAA tissues from ApoE KO mice and human patients. Moreover, Ang II infusion markedly increased the incidence and severity of AAA in ApoE KO mice, which was considerably reduced in LMP7/ApoE dKO mice. Histological alterations, including aortic wall thickening, collagen deposition, elastin fragmentation, and vascular smooth muscle cell apoptosis in AAA tissue of ApoE KO mice, were also significantly attenuated in LMP7/ApoE dKO mice. Interestingly, LMP7/ApoE dKO mice showed a marked reduction of infiltration of CD3+ T cells, especially CD4+ T cells in AAA tissues compared with ApoE KO mice. Moreover, ablation of LMP7 substantially inhibited the differentiation of CD4+ T cells into Th1 and Th17 cells by reducing the activation of multiple transcriptional factors. We also investigated the effects of an LMP7-specific inhibitor PR-957 (also known as ONX 0914) on AAA formation in ApoE KO mice. PR-957 treatment could reduce the AAA incidence and severity. In conclusion, our results provide, to our knowledge, novel evidence that ablation or pharmacological inhibition of LMP7 attenuates Ang II-induced AAA formation, and LMP7 might be a novel therapeutic target for treating AAA in humans.

Role of Family with Sequence Similarity 3A in High Glucose-induced Oxidative Damage of Human Umbilical Vein Endothelial Cells.

Objective To investigate the role of family with sequence similarity 3A(Fam3A) in high glucose-induced damage of human umbilical vein endothelial cells (HUVECs). Methods HUVECs were divided into control group and high glucose group, which were cultured in endothelial cell medium (ECM) containing 5.5 mmol/L of glucose and ECM containing 33.3 mmol/L of glucose, respectively. Real-time quantitative polymerase chain reaction was used to detect the mRNA expression of Fam3A, whereas the protein expression of Fam3A was detected by enzyme-linked immunosorbent assay. HUVECs in control group and high glucose group were transfected with siNT and siFam3A, respectively, and the levels of reactive oxygen species(ROS), ATP, mitochondrial oxygen consumption rate(OCR), and P-p38 protein were detected.Results After HUVECs had been cultured for 24h, the relative mRNA expression of Fam3A between high glucose group and control group was 2.52±0.19 (t=13.296,P=0.000). The Fam3A protein level was (173.82±33.28)pg/ml in the high glucose group, which was significantly higher than that [(39.45±33.78)pg/ml] in the control group (t=4.907,P=0.006). The intracellular ROS content in siNT-high glucose group was (8217±794)RFU, which was significantly higher than that [(3982±398)RFU] in siNT control group (t=15.109,P=0.002). The intracellular ROS content of siFam3A high glucose group was (11 910±1 001)RFU, significantly higher than that [(4171±402)RFU] of siFam3A control group (t=9.705,P=0.010) and than that of siNT high glucose group (t=4.026,P=0.048). The relative amounts of ATP synthesis in siNT high glucose group, siFam3A control group and siFam3A high glucose group were (61.2±5.6)%, (94.6±8.4)%, and (29.7±2.7)% of the siNT control group respectively; thus, it was significantly lower in siNT high glucose group than in siNT control group (t=12.001,P=0.007) and was also significantly lower in siFam3A high glucose group than in siFam3A control group (t=20.742,P=0.002) and in siNT high glucose group(t=18.814,P=0.003). The mitochondrial OCR was (0.57±0.05)pMO2/(µg protein·min) in siNT high glucose group, significantly lower than that [(1.12±0.09)pMO2/(µg protein·min)] of siNT control group (t=6.804,P=0.021). The mitochondrial OCR of siFam3A high glucose group was (0.31±0.03)pMO2/(µg protein·min), significantly lower than that [(1.01±0.09)pMO2/(µg protein·min)] of siFam3A control group (t=19.876,P=0.003), which was significantly lower than that of siNT high glucose group (t=21.444,P=0.002). The relative expression of P-p38 in siNT high glucose group, siFam3A control group, and siFam3A high glucose group was 2.239±0.353, 0.816±0.120, and 1.160±0.185, respectively; thus, it was significantly higher in the siNT high glucose group than in siNT control group (t=6.075,P=0.026); in addition, it was significantly higher in the siFam3A high glucose group than in siFam3A control group (t=6.242,P=0.024) and significantly lower than in siNT high glucose group (t=9.686,P=0.010). Conclusions High glucose can induce high expression of Fam3A in HUVECs. Knockdown of Fam3A gene expression can exacerbate the decrease of ATP synthesis and mitochondrial OCR caused by high glucose and promote the generation of ROS in high glucose. Fam3A may regulate high glucose-induced ROS production in HUVECs via the p38 MAPK signaling pathway.