Excimer laser atherectomy combined with drug-coated balloon angioplasty for the treatment of femoropopliteal arteriosclerosis obliterans.

INTRODUCTION: It has been reported that excimer laser atherectomy combined with a drug-coated balloon (ELA+DCB) can achieve better results than simple balloon angioplasty, especially for the treatment of femoropopliteal in-stent restenosis. However, reports on the application of ELA+DCB in China for femoropopliteal arteriosclerosis obliterans are lacking. This study focuses on analysing the effectiveness and safety of ELA+DCB. METHODS: This was a single-centre retrospective study that enrolled patients from November 2016 to January 2019 who had femoropopliteal arteriosclerosis obliterans treated by ELA+DCB. Preoperative demographics, operative details and postoperative follow-up outcomes were analysed statistically. RESULTS: There were 43 patients with an average patient age of 68.0±8.6 years; 79.1% were male. In 30 cases, the lesions were de novo and the others were in-stent restenosis (ISR). During the procedure, flow-limiting dissection (48.8%) was the main adverse event and there were 17 bailout stent implantations due to dissection. Mean (±sd) ankle-brachial index (ABI) in the patients was 0.42±0.31 before the operation and 0.83±0.13 before discharge. The mean (±sd) follow-up time was 29.35±9.71 months. The primary patency rate was 66.8%, 64.3% and 60.9% at 12, 24 and 36 months. Freedom from target lesion revascularisation (TLR) was 85.7%, 80.7% and 75.3% at 12, 24 and 36 months. Rutherford categories also greatly improved during follow-up. Overall mortality was 6.9% (3/48), and no deaths were related to the intervention. CONCLUSION: The use of ELA+DCB had good clinical benefit for femoropopliteal arteriosclerosis obliterans, which had good primary patency and freedom from TLR, although intraoperative complications still required attention. Multicentre randomised controlled trials with long-term follow-up are needed.

The Association of Cardio-Ankle Vascular Index and Ankle-Brachial Index with Macroangiopathy in Patients with Type 2 Diabetes Mellitus.

AIMS: This study elucidates the association of macroangiopathy development in type 2 diabetes patients with various arteriosclerosis risk factors (ARFs) and results of cardio-ankle vascular index (CAVI) and ankle-brachial pressure index (ABI). METHODS: The correlation between current and past macroangiopathy development, with ARFs or CAVI/ABI data, was retrospectively analyzed using multivariate logistic regression in 816 patients with type 2 diabetes at a single center. C-statistics combining some independent variables selected using the stepwise method were evaluated. RESULTS: CAVI was significantly correlated with macroangiopathies, including coronary artery disease (CAD), arteriosclerosis obliterans (ASO), and stroke with odds ratios (OR) of 1.20, 1.22, and 1.19, respectively. ABI significantly correlated with ASO and stroke with respective OR of 13.6 and 2.47, but not with CAD. Areas under the receiver operating characteristic curves (ROCs) revealed the accuracy of detecting ASO and stroke was increased by the combination of CAVI＋ABI (0.94 and 0.74, respectively). However, areas under the ROC for the presence of CAD can be increased by the combination of CAVI and ARFs especially including dyslipidemia. CONCLUSION: CAVI/ABI and some ARFs are useful tools in daily clinical care units to identify the current and past existence of macroangiopathy in patients with type 2 diabetes, but the prediction weights using these factors were different among CAD, ASO, and stroke.

Involvement of MicroRNA-133a in the Development of Arteriosclerosis Obliterans of the Lower Extremities via RhoA Targeting.

AIM: RhoA is a critical factor in regulating the proliferation and migration of arterial smooth muscle cells (ASMCs) in patients with arteriosclerosis obliterans (ASO). RhoA is modulated by microRNA-133a (miR-133a) in cardiac myocytes and bronchial smooth muscle cells. However, the relationship between miR-133a and RhoA with respect to the onset of ASO in the lower extremities is uncertain. METHODS: We employed in situ hybridization (ISH) and immunohistochemistry (IHC) to detect the location of miR-133a and RhoA in ASO clinical samples, respectively. 5-ethynyl-2'-deoxyuridine (EdU), cell counting kit-8 (CCK-8), Transwell and wound closure assays were utilized to determine the features of human ASMC (HASMC) proliferation and migration. The expression of miR-133a in the HASMCs was assessed using quantitative real-time PCR (qRT-PCR), while that of RhoA was examined via qRT-PCR and Western blotting. RESULTS: We found miR-133a and RhoA to be primarily located in the ASMCs of ASO. miR-133a was significantly downregulated in the ASO tissues and proliferating HASMCs. In contrast, RhoA was upregulated in the ASO samples. The proliferation and migration of HASMCs was markedly promoted by the downregulation of miR-133a and inhibited by the upregulation of miR-133a. The Luciferase assay confirmed that RhoA was a direct target of miR-133a. The upregulation of miR-133a in the HASMCs decreased the RhoA expression at the protein level. Inversely, the downregulation of miR-133a increased the RhoA protein expression. Of note, the overexpression of RhoA in the HASMCs attenuated the anti-proliferative and anti-migratory effects of miR-133a. CONCLUSIONS: Our data indicate that miR-133a regulates the functions of HASMCs by targeting RhoA and may be involved in the pathogenesis of ASO. These findings may lead to the development of potential therapeutic targets for ASO of the lower extremities.

Case of parathyroid carcinoma with a highly aggressive clinical course.

We describe a 59-year-old woman who presented with pathological osteoporosis, cerebral infarction, hypercalcemia, and markedly high parathyroid hormone levels. The diagnosis was primary hyperparathyroidism, and parathyroidectomy was performed. Histopathological examination showed parathyroid adenoma. Surgical exploration for recurrent parathyroid carcinoma was undertaken at 2 and 3 years after the initial neck resection. Pulmonary metastasis was diagnosed at 4 years after the initial surgery.Despite treatment with intravenous bisphosphonates, her calcium and parathyroid hormone (PTH) levels remained elevated, and leg amputation was performed following the development of arteriosclerosis obliterans at 6 years after the initial neck resection. The prognosis for parathyroid carcinoma is often difficult to predict due to recurrence.

Attenuation of transplant arteriosclerosis by oral feeding of major histocompatibility complex encoding chitosan-DNA nanoparticles.

One promising approach for the induction of transplant tolerance is the pre-treatment of transplant recipients with donor MHC-alloantigen. Our study focuses on the oral delivery of MHC-antigen encoding genes via chitosan-DNA nanoparticles to modulate the alloimmune response in order to reduce the development of transplant arteriosclerosis, the hallmark feature of chronic rejection after heart transplantation. Therefore, we performed fully allogeneic mouse abdominal aortic transplants using C57BL/6 (H2(b)) mice as donors and CBA.J (H2(k)) mice as recipients. Aortic grafts were analyzed by histology and morphometry on day 30 after transplantation, levels of circulating alloantibodies were detected by FACS analysis. Pre-treatment of recipient mice with chitosan-DNA nanoparticles encoding for K(b), one of the MHC-I molecules of the donor, resulted in a significant reduction of intimal proliferation compared to untreated controls. When Ovalbumin was fed instead of K(b) encoding nanoparticles (K(b)-NP) or Balb/c (H2(d)) grafts were used instead of C57BL/6 (H2(b)) grafts as antigen controls, both groups showed no reduction of intimal thickness indicating an antigen-specific mechanism. In addition, analysis of peripheral blood of the transplanted mice showed significant suppression of alloantibody formation in the K(b)-NP fed group compared to all other allogeneic transplanted groups suggesting modulation of the humoral immune response. These results demonstrate the potential of chitosan-DNA nanoparticles to induce K(b)-specific tolerance and to reduce the development of transplant arteriosclerosis.

Anti-phospholipid antibodies contribute to arteriosclerosis in patients with systemic lupus erythematosus through induction of tissue factor expression and cytokine production from peripheral blood mononuclear cells.

INTRODUCTION: In systemic lupus erythematosus (SLE) patients, the prevalence of arteriosclerosis obliterans (ASO) is high despite a lack of common risk factors for ASO. The main objective of this study was to investigate a possible direct role of anti-phospholipid antibodies (aPLs), which are frequently detected in SLE patients, in the pathogenesis of ASO. MATERIALS AND METHODS: We examined tissue factor (TF) expression on the monocyte surface by flow cytometric analysis in 89 SLE patients with or without ASO and/or aPLs and studied the in vitro effect of purified IgG fractions from plasma of SLE patients or normal healthy volunteers (aPLs(+) IgG, n=8; aPLs(-) IgG, n=6; Normal IgG, n=6) on the expression of TF and production of TNF-α and IL-1ß in healthy peripheral blood mononuclear cells (PBMCs) or isolated monocytes. RESULTS: We confirmed that high expression of monocyte TF was strongly associated with the prevalence of ASO and the presence of aPLs. Treatments of PBMCs with aPLs(-) IgG or normal IgG did not significantly increase expression of TF, TNF-α, and IL-1ß messenger RNA (mRNA) and the production of TNF-α and IL-1ß. However, stimulation of PBMCs with aPLs(+) IgG caused significant increase in expression of TF, TNF-α, and IL-1ß mRNA. Moreover, aPLs(+) IgG stimulated PBMCs and significantly enhanced the production of TNF-α and IL-1ß. CONCLUSION: These results suggest that IgG-aPLs cause persistently high TF expression and inflammatory cytokine production by interacting with peripheral blood monocytes and lymphocytes, which may be an important mechanism in the pathogenesis of ASO peculiar to SLE patients.

MicroRNA-21 regulates vascular smooth muscle cell function via targeting tropomyosin 1 in arteriosclerosis obliterans of lower extremities.

OBJECTIVE: The goal of this study was to determine the expression signature and the potential role of microRNAs in human arteries with arteriosclerosis obliterans (ASO). METHODS AND RESULTS: The expression profiles of microRNAs in human arteries with ASO and in normal control arteries were determined by quantitative reverse transcription-polymerase chain reaction array. Among the 617 detected microRNAs, multiple microRNAs were aberrantly expressed in arteries with ASO. Some of these dysregulated microRNAs were further verified by quantitative reverse transcription-polymerase chain reaction. Among them, microRNA-21 (miR-21) was mainly located in arterial smooth muscle cells (ASMCs) and was increased by more than 7-fold in ASO that was related to hypoxia inducible factor 1-α. In cultured human ASMCs, cell proliferation and migration were significantly decreased by inhibition of miR-21. 3'-Untranslated region luciferase assay confirmed that tropomyosin 1 was a target of miR-21 that was involved in miR-21-mediated cellular effects, such as cell shape modulation. CONCLUSION: The results suggest that miR-21 is able to regulate ASMC function by targeting tropomyosin 1. The hypoxia inducible factor-1 α/miR-21/tropomyosin 1 pathway may play a critical role in the pathogenesis of ASO. These findings might provide a new therapeutic target for human ASO.

[The experience with thoracoscopic sympathectomy for the treatment of distal lesions of limb arteries].

The study included 107 patients with distal lesions of limb arteries treated with the use of thoracoscopic sympathectomy. The best results in the early postoperative period were obtained in patients with Raynaud's disease. Modifications introduced into the methods of its treatment permitted to retain effectiveness of sympathectomy till the late postoperative period in 90% of the patients. Surgery for obliterative endarteritis and atherosclerosis was viewed as a possibility to preserve the supporting function of the limb. This purpose was attained in 73.2 and 62.5% of the patients respectively in the early and in 62 and 25% in the late postoperative periods.

Risk of macrovascular disease stratified by stage of chronic kidney disease in type 2 diabetic patients: critical level of the estimated glomerular filtration rate and the significance of hyperuricemia.

BACKGROUND: Although a high prevalence of macrovascular disease (MVD) has been reported in patients with stage 3 chronic kidney disease (CKD), few studies have reported its risk with respect to the underlying cause of kidney disease. This study investigated the prevalence of MVD in type 2 diabetic patients with CKD stratified by CKD stage, as defined by estimated glomerular filtration rate (eGFR), as well as the risk factors for MVD. METHODS: 1493 patients with diabetic CKD (1273 males, 220 females) were stratified by CKD stage (stage 1: 39, stage 2: 272, stage 3: 1052, stage 4: 101, stage 5: 29) based on eGFR calculated by the Japanese formula and averaged over 8 months. MVD was defined as one of the following: coronary heart disease (CHD), stroke or arteriosclerosis obliterans (ASO). RESULTS: The prevalence of MVD was 18.6%. A significant increasing trend in MVD prevalence was observed from stage 3 (17.78%) to 4 (52.48%). According to a receiver operating characteristic curve analysis on MVD prevalence in stage 3 patients, an eGFR of 46.4 ml/min/1.73 m(2) was determined to be a critical cut-off level. Proteinuria, eGFR <60 ml/min/1.73 m(2) and hyperuricemia were independent risk factors for MVD. CONCLUSIONS: In patients with diabetic CKD, a significant increase in MVD prevalence was observed from stage 3 to 4. An eGFR of 46.4 ml/min/1.73 m(2) is a critical level that affects MVD prevalence. From the perspective of cardiorenal association, CKD stage 3 should be divided into two substages. As hyperuricemia is related to an increased risk of MVD, uric acid control may be important in reducing MVD risk in diabetic CKD.

[Management of prosthetic graft occlusion after lower extremity bypasses].

OBJECTIVE: Report the experience of management of graft occlusion in patients with lower extremity bypasses and discuss the appropriate treatment strategy. METHODS: From Oct. 2004 to Oct. 2009, 104 cases of graft occlusion were treated in 53 patients with lower extremity arterial bypasses, including medical therapy for 10 cases and redo operations for 94 cases: graft thrombectomy alone for 26 cases, redo bypass or extension bypass with prosthetic or autologous vein grafts for 23 cases, graft thrombectomy plus balloon angioplasty for 18 cases, major amputation for 14 cases, graft thrombectomy plus femoral or popliteal artery endarterectomy for 10 cases, removal of occluded graft with infection for 2 case, and autologous stem cell transplantation for 1 case. RESULTS: 77 reconstructive procedures were applied and graft failures recurred in 49 cases (63.6%). One patient died of acute renal failure during peri-operative period and 9 patients died during follow-up; 6 patients were lost to follow-up. The remaining 37 patients were followed: major amputation for 12 patients, patent grafts after reconstruction in 18 patients, and medical therapy after graft occlusion for 7 patients with limb salvage. Kaplan-Meier survival analysis revealed 3-year survival of 77.4%, limb salvage of 64.7%, and graft patency of 45.7%. Effect of different procedures on cumulative patency was of no statistical significance. CONCLUSIONS: Graft occlusions after lower extremity bypasses may result in high rate of reocclusion and amputation. Optimal management should be based on a thorough analysis of individual condition.

Characteristics of revascularization treatment for arteriosclerosis obliterans in patients with and without hemodialysis.

BACKGROUND: Limb ischemia is a major complication in patients who are receiving hemodialysis (HD). In this study, distinctive features and factors affecting the outcome of HD patients with limb ischemia are identified. METHODS AND RESULTS: One hundred and eighty consecutive symptomatic limb ischemic patients who were or were not receiving HD and who successfully underwent surgical bypass grafting (bypass, n=75) or endovascular angioplasty (percutaneous transluminal angioplasty (PTA), n=105) were retrospectively compared at our hospital. The endpoint of this study was amputation of the ischemic leg or death. Median follow up was 2.25 years. The amputation-free survival of HD patients was significantly lower than that of non-HD patients (P<0.0001). In the bypass group, the amputation-free survival of HD patients was significantly lower than that of non-HD patients (P=0.0002), even if the graft was patented or not (P=0.77). In contrast, in the PTA group, the amputation-free survival of HD patients was lower than that of non-HD patients (P=0.03), and with a significantly lower patency rate (P=0.0004). Predictors of amputation-free survival differed between HD and non-HD patients; predictors were diabetes mellitus and gender in HD patients, while they were Fontaine classification and hyperlipidemia in non-HD patients. The infectious death rate was higher in HD patients than in non-HD patients (53% vs 22%, P<0.05). CONCLUSIONS: This study clearly showed a poorer prognosis in HD patients than in non-HD patients especially after bypass surgery, even if the the graft was patented or not.

[Ultrastructural changes of vascular endothelium in patients with chronic ischemia of the extremities after conduction of multipotent stromal cells from adipose tissue transplantation].

Taking into account the impossibility of performance in some situations of reconstructive operative interventions on arteries, it is necessary to look for new methods of indirect revascularization for the extremities ischemia. Adipose tissue constitutes an accessible and sufficient source of multipotent stromal cells (MSC). Experimental investigations were made in a frame of preclinical trial on laboratory animals with the extremity ischemia simulation, and there was proved the essential stimulation of angiogenesis processes after transplantation performance of stromal-vascular fraction of adipose tissue. The work objective was to study the influence of own adipose tissue MSC transplantation on vascular endothelium changes in patients, suffering chronic ischemia of the extremities. Using electron microscopy method there was proved on microstructural level, that in clinical environment the patients, suffering chronic ischemia of the extremities of various etiology, gain undoubted effect of MSC autotransplantation performed with the objective to stimulate the processes of angiogenesis in the ischemic affection region.

[Long-term results of dyslipoproteinemia surgical correction in patients with obliterating atherosclerosis of the lower extremity].

An analysis of long-term (up to 20 years) results of performing operations of partial ileoshunting as a method of surgical correction of dislipoproteidemia in 49 patients with obliterating atherosclerosis of the lower extremity vessels has shown that operations of partial ileoshunting have a pronounced and stable lipid correcting effect. Decreased level of atherogenic lipids in blood improved the course of obliterating atherosclerosis of the lower extremity vessels. Worse long-term clinical results after partial ileoshunting were in a considerable degree due to the presence of residual dislipoproteidemia that resulted in additional medicamentous hypolipidemic therapy.

[Haemodynamic role of blood-plasma circulating cell-free DNA and contained therein high-molecular-weight CpG-rich fraction in pathogenesis of arterial hypertension and atherosclerosis obliterans of carotid arteries].

The hydrodynamic resistance (HR) of blood is one of the components of the total peripheral resistance. High-molecular-weight DNA appears to decrease the HR in accordance with the Toms's effect. The present study was undertaken to investigate the HR and properties of cell-free DNA circulating in the blood plasma (hereinafter referred to as pDNA) of the control donors, patients suffering from either arterial hypertension (AH) alone or that combined with atherosclerotic lesions of the carotid arteries (CAs). Within the normal concentrations of pDNA, we revealed an inverse dependence of the HR thereupon and upon the content in pDNA of the high-molecular-weight CpG-rich fraction (CpG-DNA), i. e., a transcribed region of the ribosomal repeat (rDNA). A decrease or an increase in the pDNA concentration in all the patients examined was accompanied by an elevation of the rDNA concentration in the blood plasma. Exceeding a certain level thereof appeared to give rise to an increase in both the HR and arterial pressure (AP). Patients presenting with degree I essential AH were found to have a decreased endonuclease activity of the blood plasma, with the pDNA concentration being more than two-fold higher with no change in the rDNA content. Their HR appeared to be increased (p<0.01). Patients diagnosed as having degree II AH were characterized by a normal or decreased level of pDNA and an elevated content of pDNA, with the HR being slightly lowered. In patients presenting with atherosclerosis obliterans of the ACs, the initial manifestations of the lesions of the carotid arteries were typically revealed on the background of a lowered HR (p<0.05). All patients suffering from atherosclerotic lesions of the ACs could be subdivided into two groups, which in our opinion is probably associated with different various mechanisms of destructive damage to the arterial intima. In some of them, the pDNA concentration does not differ from the normal values, but in its composition, there is an increased content of rDNA, elevating as obliteration of the vessels' lumen increases, with the HR being decreased. The majority of them have degree II AH. In others, the pDNA concentration is by an order of magnitude higher than the normal values, while the rDNA content in pDNA is decreased, with the HR being elevated. Most of them have degree III AH. Pronounced and rough stenoses take an asymptomatic course in patients with decreased values of the HR and a slightly elevated level of pDNA and/or rDNA in the blood plasma. A higher level thereof leads to a rise in the HR and to the appearance of neurological symptomatology. Hence, CpG-DNA circulating in the composition of pDNA is a constantly acting endogenous blood factor decreasing the HR (the Toms's effect) and normalizing AP under physiological conditions, being however a cause of their increase and impairment of blood circulation in the pathogenesis of AH and atherosclerosis obliterans of the CAs.

[Treatment of lower extremity diabetic atherosclerotic obliterans with shuxuetong injection].

OBJECTIVE: To observe the effect and safety of Shuxuetong Injection (SXT) in treating patients with type 2 diabetes mellitus accompanying lower extremity atherosclerotic obliterans. METHODS: The selected patients were assigned by randomized digital table to the treated group (180 cases treated with SXT) and the control group (80 cases treated with alprostadil). The clinical efficacy was assessed after 4 weeks of treatment, and the inner diameters and blood flow of the superficial femoral artery, the posterior tibial artery and the foot dorsal artery were measured and compared before and after treatment using Doppler's ultrasonography. RESULTS: The total effective rate in the treated group was 94.4% (170/180), better than that in the control group, 85.0% (68/80, P < 0.01). Ultrasonic examination showed that the inner diameter and the blood flow of all the arteries measured in the treated groups increased after treatment (P < 0.01), with the increase superior to those in the control group (P < 0.05). No adverse reaction was found during the treatment. CONCLUSION: SXT has the effect of activating blood circulation, dissolving stasis and dredging collaterals, it could reduce or eliminate the formation of thrombi, being effective and safe when applied in clinical practice for the treatment of lower extremity diabetic atherosclerotic obliterans.

[Hemorheologic disturbances in patients with obliterative atherosclerosis of peripheral arteries and type 2 diabetes mellitus].

The aim of this work was to assess hemorheologic variations and factors influencing them in 529 patients with obliterative atherosclerosis of the lower limbs and type 2 diabetes mellitus. Blood viscosity and hematocrit volume were measured. Statistical treatment of the results was performed using the STATISTICA 6.0program (StatSoft Inc., USA). Differences between observed and normal distributions were described in terms of medians and quartiles. Independent groups were compared using Mann-Whitney U-test, 2-sample Kolmogorov-Smirnov test, and Kruskal-Wallis method. Differences were considered significant atp < 0.05. Results of the study confirm disturbances in the hemorheologic system in patients with obliterative atherosclerosis of the lower limbs and diabetes. Variations of blood viscosity and hematocrit volume in these patients have multidimensional character and depend on such factors as age, gender, smoking, duration of diabetes, degree of compensation of metabolic processes, and severity of arterial circulation problems.