CircHAT1 regulates the proliferation and phenotype switch of vascular smooth muscle cells in lower extremity arteriosclerosis obliterans through targeting SFRS1.

This study aimed to decipher the mechanism of circular ribonucleic acids (circRNAs) in lower extremity arteriosclerosis obliterans (LEASO). First, bioinformatics analysis was performed for screening significantly down-regulated cardiac specific circRNA-circHAT1 in LEASO. The expression of circHAT1 in LEASO clinical samples was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of splicing factor arginine/serine-rich 1 (SFRS1), α-smooth muscle actin (α-SMA), Calponin (CNN1), cyclin D1 (CNND1) and smooth muscle myosin heavy chain 11 (SMHC) in vascular smooth muscle cells (VSMCs) was detected by Western blotting. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assays were used to evaluate cell proliferation and migration, respectively. RNA immunoprecipitation (RNA-IP) and RNA pulldown verified the interaction between SFRS1 and circHAT1. By reanalyzing the dataset GSE77278, circHAT1 related to VSMC phenotype conversion was screened, and circHAT1 was found to be significantly reduced in peripheral blood mononuclear cells (PBMCs) of LEASO patients compared with healthy controls. Knockdown of circHAT1 significantly promoted the proliferation and migration of VSMC cells and decreased the expression levels of contractile markers. However, overexpression of circHAT1 induced the opposite cell phenotype and promoted the transformation of VSMCs from synthetic to contractile. Besides, overexpression of circHAT1 inhibited platelet-derived growth factor-BB (PDGF-BB)-induced phenotype switch of VSMC cells. Mechanistically, SFRS1 is a direct target of circHAT1 to mediate phenotype switch, proliferation and migration of VSMCs. Overall, circHAT1 regulates SFRS1 to inhibit the cell proliferation, migration and phenotype switch of VSMCs, suggesting that it may be a potential therapeutic target for LEASO.

[Carotid artery stenosis treated with modified carotid endarterectomy: report of two cases].

OBJECTIVE: Based on standard carotid endarterectomy, we performed modified carotid endarterectomy in two cases of carotid artery stenosis by changing the direction of the carotid artery incision to avoid restenosis of the internal carotid artery without using a patch. The two patients recovered smoothly without any complications. Compared with eversion or patch endarterectomy, this modified carotid endarterectomy avoids restenosis of the carotid artery and shortens operation time.

Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression.

Angiogenesis plays a critical role in the progression and vulnerability of atherosclerotic plaques; however, the orchestration of angiogenesis in atherosclerotic plaque formation remains unclear. The results of microarray analysis, real-time PCR and immunohistochemical analyses showed that Hairy/enhancer of split homologue-1 (Hes-1) expression was significantly decreased, while that of osteopontin (OPN) was increased, in atherosclerotic plaques. Meanwhile, immunofluorescence results demonstrated that both Hes-1 and OPN were expressed in endothelial cells (ECs) of neovessels in atherosclerotic plaques. The results of an in vitro study showed that Hes-1 was downregulated, while OPN was upregulated, in a time- and dose-dependent manner in human umbilical vein endothelial cells (HUVECs) by VEGF treatment. In addition, Hes-1 knockdown was found to have transcriptional promotion effect on OPN expression in HUVECs and enhance OPN-induced angiogenesis in response to VEGF. On the contrary, Hes-1 overexpression inhibited OPN expression in HUVECs and reduced angiogenesis in vitro and in vivo. The results of this study suggest that decreased Hes-1 expression in atherosclerotic plaques exaggerate VEGF-induced angiogenesis by upregulating OPN. Therefore, restoring Hes-1 expression and inhibiting OPN expression may be a promising strategy to prevent vulnerable plaque formation in patients with atherosclerosis.

[Hybrid operation for acute left leg deep venous thrombosis secondary to left iliac vein compression syndrome: analysis of 36 cases].

OBJECTIVE: To evaluate the surgical techniques for acute left deep venous thrombosis (LDVT) secondary to left iliac vein compression syndrome (IVCS). METHODS: Thirty-six patients with acute LDVT secondary to IVCS received inferior vena cava filter placement, and in 2 of the cases, stent implantation was canceled for acute episode of obsolete DVT. The remaining 34 patients underwent left femoral venotomy for iliofemoral thrombectomy with Fogarty catheter and distal femoral vein thrombus removal by sequential compression of the legs, followed by implantation of stent-graft (2 cases) or bare-metal stents (32 cases) in the left common iliac veins. With routine anticoagulation and thrombolytic treatments, the patients were regularly examined for postoperative blood flow in the affected limb. RESULTS: In 2 of the cases undergoing bare-metal stent implantation, the residue thrombi were squeezed into the stent by balloon, which was managed subsequently with local thrombolysis. One patient with bare-metal stent implantation received a secondary stenting for posterior stent displacement. Three patients had self-limited bleeding due to decreased serum FBG. Significant improvements were achieved at 3, 6, 30 and 180 days postoperatively in the circumferences of the affected limb (P<0.05) and in the levels of D-dimer (P=0.011), and FBG level showed no significant variations (F=1.163, P=0.345). The total rate of excellent outcomes was 83.3% (26/34) with a total effective rate of 91.2% (31/34) in these cases. CONCLUSIONS: Thrombectomy to revascularize the inflow tract and stent implantation to enlarge stenosed iliac veins are key issues in treatment of acute LDVT secondary to IVCS.

[Efficacy of regional administration of urokinase and argatroban via small saphenous vein catheter for treatment of acute deep venous thrombosis in the lower limb].

OBJECTIVE: To investigate the clinical value of local regional administration of urokinase and argatroban through small saphenous vein (SSV) catheter in the treatment of acute deep venous thrombosis in the lower limb (LDVT). METHODS: Fifty-six patients with acute LDVT were prospectively randomized into the study group (21 cases, 24 limbs) and control group (35 cases, 36 limbs) for treatment with urokinase and argatroban regionally administered via the SSV catheter and with the same agents given via the peripheral vein, respectively. The patients were examined for changes in serum fibrinogen (FBG) and D-dimer and the perimeter of the affected limbs, and the complications in relation to the agents were observed. RESULTS: By corrected Chi-square test, the incidence of complications was significantly lower in the study group than in the control group (1/21 vs 4/36, χ(2)=1.92, P≤0.05). Wilcoxon's sign rank test suggested no statistically significant difference between the two groups in the total effective rate (95.8% vs 94.4%, V=0.52, P>0.05), but the total excellent rate differed significantly between them (83.3% vs 55.6%, V=2.36, P≤0.05). Serum FBG underwent no significant variations in the study group during thrombolysis (P>0.05), but decreased significantly in the control group (P≤0.05). The decreases in serum D-dimer and perimeter of the affected limbs occurred earlier in the study group than in the control group (P≤0.05). CONCLUSION: Regional administration of urokinase and argatroban via small saphenous vein catheter can promote the thrombolytic effect and reduce the risk of hemorrhage in the treatment of LDVT.

[Experience with endovenous laser treatment combined with high ligation and Muller's phlebectomy for C3-6 grade primary superficial varicose in the lower limbs].

OBJECTIVE: To summarize the experience with endovenous laser treatment(EVLT) combined with high ligation and Muller's phlebectomy for primary superficial varicose in the lower limbs. METHODS: In 95 patients with C3-6 grade primary superficial varicose in 146 lower limbs, the extent of varicose was accurately marked, the guiding wires were manipulated precisely, and the proximal great saphenous veins (GSV) were ligated after exsanguinations. The stems of the GSV were ablated with laser with the lower limbs lift up and pressed hard along the stems, and Muller's incisions were carefully planned. RESULTS: All the operations were completed successfully. The guiding wires entered into the deep veins through the communicating branches in 2 limbs, 1 patient experienced capillary hemorrhage from Muller's incisions, 8 had thrombotic phlebitis of the GSV, 7 sustained heat-related injury of the saphenous nerves, 1 experienced skin heat-related lesion, 2 developed hematoma in the inguinal region, 2 had pitting edema in the dorsum of the foot, 1 had fat liquefaction of the Muller incision, and 1 showed rejection of the thrum. After conservative treatment, all the patients recovered and were discharged. Part of the superficial varicose remained after the operation in 6 limbs. CONCLUSION: It is necessary to standardize the routine procedure of EVLT combined with high ligation and Muller's phlebectomy to reduce the complications.