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Vascular endothelial cell functions affect lower extremity arteriosclerosis obliterans (LEASO), while alpha-2-macroglobulin (A2M) and CCCTC-binding factor (CTCF) are closely related to the function of such cells. This paper aims to identify the influences of CTCF on vascular endothelial cells in LEASO by regulating A2M. A rat model of LEASO was established to measure intima-media ratio, blood lipid, and inflammatory factor levels. By constructing LEASO cell models, cell viability and apoptosis were assayed, while autophagy-related proteins, CTCF and A2M levels in femoral artery tissues and HUVECs were determined. The transcriptional regulation of CTCF on A2M was verified. In LEASO rat models, femoral artery lumen was narrowed and endothelial cells were disordered; levels of total cholesterol, IL-1, and TNF-α enhanced, and HDL-C decreased, with strong expression of A2M and low expression of CTCF. The viability of ox-LDL-treated HUVECs was decreased, together with higher apoptosis, lower LC3II/I expression, and higher p62 expression, which were reversed by sh-A2M transfection. Overexpression of CTCF inhibited A2M transcription, promoted the viability and autophagy of HUVECs, and decreased apoptosis. Collectively, CTCF improves the function of vascular endothelial cells in LEASO by inhibiting A2M transcription.

In this study, we investigated the impact of microRNA-34a (miR-34a) on lower limb arteriosclerosis obliterans in rats through the Sirtuin 1 (Sirt1) signaling pathway. Thirty-six Sprague-Dawley rats were divided into normal, model, and miR-34a mimics groups. Rats in the normal group were raised normally, while the model group underwent lower limb arteriosclerosis obliterans induction and received saline injections. The miR-34a mimics group also underwent arteriosclerosis obliterans modeling but received miR-34a mimics injections. Immunohistochemistry revealed significantly increased vascular endothelial growth factor (VEGF) expression in both model and miR-34a mimics groups compared to the normal group, with the miR-34a mimics group showing higher levels. Western blotting indicated elevated Sirt1 protein expression in both non-normal groups, with the miR-34a mimics group exhibiting significantly higher levels. Quantitative polymerase chain reaction (qPCR) demonstrated higher levels of miR-34a, VEGF mRNA, and Sirt1 mRNA in the model group compared to the normal group, but significantly lower levels than the miR-34a mimics group. Enzyme-linked immunosorbent assay (ELISA) showed increased VEGF content in the model group compared to the normal group but decreased compared to the miR-34a mimics group. Hemorrheological detection revealed a reduced PU index in both non-normal groups compared to the normal group, with a significant increase in the miR-34a mimics group compared to the model group. Overall, miR-34a upregulation enhanced VEGF expression in rat blood vessels, ameliorating arterial blood flow in lower limb arteriosclerosis obliterans through the Sirt1 signaling pathway.

Introduction: The disease arteriosclerosis obliterans (ASO) affects the lower extremities. ASO's mechanism involves the proliferation and migration of vascular smooth muscle cells (VSMCs). The miR-4284 is involved in several biological processes of the cardiovascular system, including VSMC proliferation, migration, and death. However, it is unknown if the miR-4284 gene is involved in the control of ASO. Furthermore, the molecular processes behind the contribution of human arterial smooth muscle cells (HASMCs), one of the most significant components of the arterial wall, to arteriosclerosis obliterans (ASO) pathogenesis remain unknown. Previously, we explored the alterations of miRNAs in the blood of ASO patients, and now we wanted to test further whether these changes also take place in the HASMCs that are responsible for the pathogenesis of ASO., Methods: The expression levels of miR-29a in arterial walls were analyzed via a real-time polymerase chain reaction. An ASO cell model was established to investigate the expression of miR- 4284 on HASMCs. The Transwell system and CCK-8 detection were used to assess the migration and proliferation of HASMCs. The proportion of apoptotic cells as well as the concentrations of apoptotic signal protein production were assessed using flow cytometry. A Western blot technique was used to identify B cell lymphoma-2 (Bcl2), Bcl2-associated X protein (BAX), as well as Xlinked inhibitors of apoptosis protein (XIAP)., Results: The results showed that PCR confirmed that the qualified production or expression of miR-4284 was significantly reduced in HASMCs after they were cultured without FBS and in an atmosphere of 1% O 2 + 5% CO 2 + 94% N 2 and that glucose had no effect on its expression. MiR- 4284 has no effect on migration and proliferation, but downregulation of miR-4284 can decrease the apoptotic rate of HASMCs, as revealed by flow cytometry. Furthermore, western blot experiments showed that the expression of BAX was low, while the expression of the other two proteins, viz., Bcl2 and XIAP, was over-expressed., Conclusion: We found that miR-4284 downregulation enhanced Bcl2, as well as XIAP, and decreased Bax. This shows that downregulated miR-4284 regulates apoptosis-related protein expression in HASMCs. The mechanism is not clear, and we need further study to confirm it., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

An increasing number of studies have shown that noncoding RNAs are involved in cardiovascular diseases. Our study shows that the expression of microRNA-30a-3p (miR-30a-3p) in patients with arteriosclerosis obliterans (ASO) of the lower extremities is significantly decreased after endovascular treatment, but its role is unclear. This study aims to explore the role of microRNA-30a-3p in ASO and its related mechanisms. Immunofluorescence and in situ hybridization costaining indicated that microRNA-30a-3p mostly exists in vascular smooth muscle cells (VSMCs). Furthermore, after transfection into VSMCs, microRNA-30a-3p inhibited VSMC proliferation, migration and phenotype switching. In addition, luciferase reporter and western blot analyses indicated that ROCK2 (Rho-related spiral coil 2 containing protein kinase) is a microRNA-30a-3p target gene, and participates in the microRNA-30a-3p mediated cell inhibitory effect. At last, the rat carotid artery was infected by lentivirus after balloon injury, which increased microRNA-30a-3p levels and apparently suppressed the formation of neointima in vivo . Overall, exogenous introduction of microRNA-30a-3p, a noncoding RNA with unlimited potential, may be a new approach to treat ASO.

This work was aimed to explore the effect of recombinant netrin-1 protein and peripheral blood mesenchymal stem cells (MSCs) on the angiogenesis ability of atherosclerosis. 28 Sprague Dawley (SD) rats were taken as research models. The arterial occlusion models were created by surgery and then divided into the saline control group ( n  =7), netrin-1 treatment group ( n  =7), MSCs treatment group ( n  =7), and netrin-1 + MSCs combined treatment group ( n  =7). The peripheral blood MSCs were extracted from the peritoneal cavity of diseased SD rats and cultured alone or in combination with netrin-1. The individually cultured MSCs and netrin-1 were locally injected into the ischemic tissues of SD rats. The Tarlov scoring was performed at the first, second, and third week of treatment, respectively. The expression of vascular endothelial growth factor (VEGF) was also measured by quantitative real-time polymerase chain reaction (qRT-PCR), and the capillary density was measured by immunofluorescence staining. The mean maximum contractility of the gastrocnemius muscle in each group was determined in the third week after treatment. The Tarlov score of the netrin-1 + MSCs group was significantly higher than that of the control group ( P < 0.05) at the second week. To the 4th week of treatment, the Tarlov score of the netrin-1 + MSCs group was highly increased compared to the netrin-1 group and the MSCs group ( P < 0.05). The expression of VEGF in the treatment groups was greatly increased each week compared to the control group ( P < 0.05). Compared with the netrin-1 and the MSCs groups, the VEGF was also notably increased in the netrin-1 + MSCs group ( P  <0.05). The capillary densities of the treatment groups were observably greater than that of the control group in the second and third weeks ( P  <0.05), while the capillary density in the netrin-1 + MSCs group was also significantly increased than those in the netrin-1 group and the MSCs group ( P < 0.05). The mean maximum contractility of the netrin-1 + MSCs group was remarkably higher than that of the other groups ( P < 0.05). The netrin-1 + MSCs group achieved the higher Tarlov score, higher VEGF expression, higher capillary density, and better muscle recovery than netrin-1 and MSCs treatments., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jie Zeng et al.)

Long non‑coding RNAs (lncRNAs) affect atherosclerosis by regulating the physiological and pathological processes of endothelial cells; however, the role of lncRNA WEE2 antisense RNA 1 (WEE2‑AS1) in arteriosclerosis obliterans (ASO) is not completely understood. The present study aimed to explore the function of lncRNA WEE2‑AS1 in human vascular endothelial cells. The results indicated that lncRNA WEE2‑AS1 was significantly elevated in plasma and artery tissue samples of patients with ASO compared with healthy controls. The fluorescence in situ hybridization results suggested that lncRNA WEE2‑AS1 was expressed in the cytoplasm and nuclei of primary human umbilical vein endothelial cells (HUVECs). The Cell Counting Kit‑8 assay results suggested that lncRNA WEE2‑AS1 knockdown significantly promoted HUVEC viability, whereas lncRNA WEE2‑AS1 overexpression inhibited HUVEC viability compared with the negative control groups. Furthermore, analysis of the cell cycle by flow cytometry indicated that lncRNA WEE2‑AS1 knockdown significantly decreased the proportion of cells in the G0/G1 phase and significantly increased the proportion of cells in the G2/M phase compared with the negative control group. However, lncRNA WEE2‑AS1 overexpression had no significant effect on cell cycle distribution compared with the negative control group. The western blotting results indicated that lncRNA WEE2‑AS1 knockdown significantly reduced the expression levels of phosphorylated cyclin dependent kinase 1, WEE1 homolog 2 and myelin transcription factor 1, but increased the expression level of cell division cycle 25B compared with the negative control group. lncRNA WEE2‑AS1 overexpression displayed the opposite effect on protein expression. Collectively, the present study suggested that lncRNA WEE2‑AS1 was significantly upregulated in ASO and may serve a role in regulating human vascular endothelial cell viability. Further investigation into lncRNA WEE2‑AS1 may broaden the current understanding of the molecular mechanism underlying ASO, and aid with the identification of specific probes and precise targeted drugs for the diagnosis and treatment of ASO.

BACKGROUND The aim of this study was to further clarify the effects of valsartan on restenosis in patients with arteriosclerosis obliterans of the lower extremities. MATERIAL AND METHODS Patients with arteriosclerosis obliterans of the lower extremities undergoing continuous stent implantation in the superficial femoral artery were enrolled and randomly divided into an ARB group and a control group. Patients in the ARB group received valsartan orally in a single-blind manner and were followed up for 6 months. An evaluation was performed based on the criteria for clinical efficacies designed by the Committee of Vascular Disease, Chinese Association of Integrative Medicine. The total clinical effective rate was calculated, and ankle brachial index (ABI) of the patients was assessed. The concentrations of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were measured using enzyme-linked immunosorbent assay. The in-stent restenosis of patients was examined by angiography. RESULTS One patient in the control group died due to acute cerebral hemorrhage 4 months after enrollment, and 1 patient was lost to follow-up due to acute myocardial infarction during follow-up 5 months after enrollment. Age, sex, Fontaine stage, and underlying diseases were comparable between the 2 groups. Hs-CRP (3.93±1.43) and IL-6 (11.26±2.29) levels were significant different in the ARB group compared with the control group. The postoperative follow-up showed that ABI was 0.98±0.20 in the ARB group and 0.62±0.48 in the control group. CONCLUSIONS Valsartan inhibited the increase in hs-CRP and IL-6 levels, improved clinical efficacies, increased ABI, and decreased the restenosis rate after the interventional therapy in patients with arteriosclerosis obliterans of the lower extremities.

Objective: To investigate the influence of micro ribonucleic acid (miR)-126 on the rats with lower limb arteriosclerosis obliterans (ASO)., Materials and Methods: Male Sprague- Dawley rats aged 3 months old were randomly divided into Sham operation group (Control group, n=10) and Model group (n=10), and the model of lower limb ASO was established. After modeling, the expression of miR-126 in arteries was detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the change in the downstream signaling pathway was examined via Western blotting. The human umbilical vein endothelial cells (HUVECs) were induced by oxidized low-density lipoprotein (Ox-LDL) to establish the model of endothelial injury, followed by detection of miR-126 expression. Then, the Luciferase assay was performed to verify the downstream target gene of miR-126. After being cultured, HUVECs were set as Control group, Ox-LDL induction group, and Ox-LDL + miR-126 inhibitor group, and the expressions of phosphorylated-protein kinase B (p-Akt) and cleaved cysteine-aspartic protease-3 (Caspase-3) were detected in the above groups., Results: After the establishment of the model, the expression level of miR-126 was raised in vessels, but the phosphatidylinositol 3-hydroxy kinase (PI3K)/Akt signals were weakened (p<0.01). Ox-LDL-induced endothelial cell apoptosis promoted the expression of miR-126, and the difference was statistically significant. The bioinformatics analysis results showed that PI3KR2 was a direct target of miR-126, which was also proven via the Luciferase assay. Moreover, the transfection with miR-126 inhibitor into endothelial cells suppressed Ox-LDL-induced cell apoptosis, thereby persistently activating the PI3K/Akt signaling pathway (p<0.01)., Conclusions: In rats with lower limb arteriosclerosis obliterans (ASO), miR-126 represses the PI3K/Akt signaling pathway to accelerate endothelial cell apoptosis.

Objective: To investigate the effect of micro ribonucleic acid (miR)-210 on the apoptosis of vascular endothelial cells in arteriosclerosis obliterans (ASO) through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway., Patients and Methods: In the present work, the vascular endothelial cells in ASO patients were selected as objects of study, the cell lines with miR-210 interference and overexpression were constructed with the Crisp/Case9 technique for subsequent experiments as experimental group, and the aortic endothelial cells of a healthy human were used as control group. First, the changes in the transcriptional and translational levels of such genes as JAK2 and STAT3 in the JAK-STAT signaling pathway in cell lines with miR-210 interference and overexpression were detected via fluorescence quantitative Polymerase Chain Reaction (qPCR) and Western blotting. The changes in the transcriptional and translational levels of nitric oxide synthase (NOS) in cells were detected in experimental group and control group to clarify the regulatory effect of miR-210 on the JAK-STAT signaling pathway. At the same time, the cell proliferation in experimental group and control group was observed via methyl thiazolyl tetrazolium (MTT) assay and the apoptosis rate was detected in both groups via flow cytometry., Results: The results of fluorescence qPCR and Western blotting revealed that the expression level of miR-210 was significantly increased in cells of ASO patients compared with that in aortic endothelial cells of healthy human with a significant difference (p<0.05). At the same time, the inhibition on miR-210 could significantly reduce the transcriptional and translational levels of JAK2, STAT3, and NOS, block the JAK-STAT signaling pathway, suppress the cell proliferation, and promote apoptosis. The overexpression of miR-210 could markedly increase the transcriptional and translational levels of JAK2, STAT3, and NOS, activate the JAK-STAT signaling pathway, promote the cell proliferation, and suppress the apoptosis., Conclusions: MiR-210 can be involved in the apoptosis process of vascular endothelial cells in ASO through the JAK-STAT signaling pathway.

Objective: To explore the effect of long non-coding ribonucleic acid (lncRNA) H19 on the apoptosis of vascular endothelial cells in arteriosclerosis obliterans (ASO) via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway., Patients and Methods: Human umbilical vein endothelial cells (HUVECs) were cultured, and lncRNA H19 was inhibited by Si-H9 and overexpressed by H19-OE. Then, the apoptosis rate was detected by flow cytometry, the target of lncRNA H19 was detected by dual luciferase reporter gene assay, and changes in the protein level were determined via Western blotting (WB)., Results: LncRNA H19 exhibited high expression in serum of patients with ASO, and compared with that in congeneric normal mice, the expression of lncRNA H19 in ASO mice rose. Besides, the proliferation ability of cells transfected with H19-OE was markedly strengthened, and H19-OE treatment could down-regulate the expression level of the apoptin, active cysteinyl aspartate-specific proteinase-3 (Caspase-3). In addition, lncRNA H19 bound to micro ribonucleic acid (miR)-19a in a targeted way. After lncRNA H19 was overexpressed, the expression of the NF-κB pathway key factors, p38 and p65, were notably increased, and the nuclear translocation of p65 was significantly enhanced after transfection with miR-19a., Conclusions: LncRNA H19 promotes the proliferation of vascular endothelial cells in ASO and inhibits the apoptosis of them via the NF-κB pathway.

Background/aims: Increasing evidence links microRNAs to the pathogenesis of peripheral vascular disease. We recently found microRNA-125b (miR-125b) to be one of the most significantly down‑regulated microRNAs in human arteries with arteriosclerosis obliterans (ASO) of the lower extremities. However, its function in the process of ASO remains unclear. This study aimed to investigate the expression, regulatory mechanisms, and functions of miR-125b in the process of ASO., Methods: Using the tissue explants adherent method, vascular smooth muscle cells (VSMCs) were prepared for this study. A rat carotid artery balloon injury model was constructed to simulate the development of vascular neointima, and a lentiviral transduction system was used to overexpress serum response factor (SRF) or miR-125b. Quantitative real‑time PCR (qRT‑PCR) was used to detect the expression levels of miR‑125b and SRF mRNA. Western blotting was performed to determine the expression levels of SRF and Ki67. In situ hybridization analysis was used to analyze the location and expression levels of miR-125b. CCK-8 and EdU assays were used to assess cell proliferation, and transwell and wound closure assays were performed to measure cell migration. Flow cytometry was used to evaluate cell apoptosis, and a dual-luciferase reporter assay was conducted to examine the effects of miR‑125b on SRF. Immunohistochemistry and immunofluorescence analyses were performed to analyze the location and expression levels of SRF and Ki67., Results: miR-125b expression was decreased in ASO arteries and platelet-derived growth factor (PDGF)-BB-stimulated VSMCs. miR-125b suppressed VSMC proliferation and migration but promoted VSMC apoptosis. SRF was determined to be a direct target of miR-125b. Exogenous miR-125b expression modulated SRF expression and inhibited vascular neointimal formation in balloon-injured rat carotid arteries., Conclusions: These findings demonstrate a specific role of the miR-125b/SRF pathway in regulating VSMC function and suggest that modulating miR-125b levels might be a novel approach for treating ASO., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background: Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and post-angioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascular smooth muscle cell (HASMC) function and neointima formation., Methods: Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect miR-22-3p expression in human arteries. Cell Counting Kit-8 (CCK-8) and EdU assays were performed to assess cell proliferation, and transwell and wound closure assays were performed to assess cell migration. Moreover, luciferase reporter assays were performed to identify the target genes of miR-22-3p. Finally, a rat carotid artery balloon-injury model was used to determine the role of miR-22-3p in neointima formation., Results: MiR-22-3p expression was downregulated in arteriosclerosis obliterans (ASO) arteries compared with normal arteries, as well as in platelet-derived growth factor-BB (PDGF-BB)-stimulated HASMCs compared with control cells. MiR-22-3p overexpression had anti-proliferative and anti-migratory effects and dual-luciferase assay showed that high mobility group box-1 (HMGB1) is a direct target of miR-22-3p in HASMCs. Furthermore, miR-22-3p expression was negatively correlated with HMGB1 expression in ASO tissue specimens. Finally, LV-miR-22-3p-mediated miR-22-3p upregulation significantly suppressed neointimal hyperplasia specifically by reducing HMGB1 expression in vivo., Conclusions: Our results indicate that miR-22-3p is a key molecule in regulating HASMC proliferation and migration by targeting HMGB1 and that miR-22-3p and HMGB1 may be therapeutic targets in the treatment of human ASO., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

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.

The migration of CD4+ T cells plays an important role in arteriosclerosis obliterans (ASO). However, the molecular mechanisms involved in CD4+ T cell migration are still unclear. The current study is aimed to determine the expression change of miR-142-3p in CD4+ T cells from patients with ASO and investigate its role in CD4+ T cell migration as well the potential mechanisms involved. We identified by qRT-PCR and in situ hybridization that the expression of miR-142-3p in CD4+ T cells was significantly down-regulated in patients with ASO. Chemokine (C-X-C motif) ligand 12 (CXCL12), a common inflammatory chemokine under the ASO condition, was able to down-regulate the expression of miR-142-3p in cultured CD4+ T cells. Up-regulation of miR-142-3p by lentivirus-mediated gene transfer had a strong inhibitory effect on CD4+ T cell migration both in cultured human cells in vitro and in mouse aortas and spleens in vivo. RAC1 and ROCK2 were identified to be the direct target genes in human CD4+ T cells, which are further confirmed by dual luciferase assay. MiR-142-3p had strong regulatory effects on actin cytoskeleton as shown by the actin staining in CD4+ T cells. The results suggest that the expression of miR-142-3p is down-regulated in CD4+ T cells from patients with ASO. The down-regulation of miR-142-3p could increase the migration of CD4+ T cells to the vascular walls by regulation of actin cytoskeleton via its target genes, RAC1 and ROCK2.

Objective: To identify distinct proteins involved in human atherosclerosis obliterans (ASO) by a differential proteomic approach., Methods: Eight atherosclerotic femoral arteries with a mean age of 68.6 years (6 male and 2 female) and 5 normal femoral arteries with a mean age of 44.2 years (3 male and 2 female) were obtained from high amputation patients. Then the first 2-dimensional maps of the proteome of human femoral arteries was plotted to compare ASO and control specimens. Proteomic profiling was to differentiate and identify histological proteins that were associated with ASO. The differentially expressed proteins were sequenced by matrix assisted laser desorption/ionization mass spectrometry (MALDI-TOF-MS). The result was verified by immunohistochemistry (IHC) and Western blot., Results: ASO was associated with distinct patterns of protein expression in the femoral arteries. A total of 25 distinct spots corresponding to 13 different proteins were identified by MALDI-TOF-MS using the NCBI and IPI databases. These proteins were mainly involved in the pathogenetic mechanisms such as inflammation, oxidative stress, proliferation and transformation of SMCs. The low level of heat shock protein 27 (HSP27) in ASO was verified by IHC and western-blot in accord with the result of MS., Conclusion: Proteomic analysis can be used to investigate differentially expressed proteins, which may provide new insights into ASO pathogenesis, such as HSP27.

Background: The architecture of the arterial wall affected with Buerger's disease has been known to be preserved in all three layers, while the one affected by arteriosclerosis obliterans (ASO) is degenerated and destroyed. We analyzed affected arteries with immunohistochemical methods to clarify the differences between Buerger's disease and ASO., Materials and Methods: Crural arteries obtained from 13 patients with Buerger's disease and 6 patients with ASO at our institute were studied. In addition, we examined seven specimens from six patients who were thought to be normal (without Buerger's disease or ASO) as negative control. Immunohistochemical studies were performed on paraffin-embedded tissues. The primary antibodies were urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-3 (MMP-3). Both are known to play an important role of extracellular proteolysis and to activate each other. Additionally, plasminogen activator inhibitor-1(PAI-1) was also examined., Results: In Buerger's disease, PAI-1 was well expressed along the internal elastic lamina. Urokinase-type plasminogen activator and MMP-3 were slightly positive in intima and media. In ASO, a slight amount of PAI-1 was recognized on vessel walls, and both uPA and MMP-3 were strongly positive in media. In addition, in the control group, PAI-1, uPA, and MMP-3 were well expressed in media., Conclusion: In Buerger's disease, PAI-1 was strongly expressed around the internal elastic lamina, while both uPA and MMP-3 were slightly recognized on vessel walls. These findings could be one of the reasons the general architecture of vessel walls in Buerger's disease is preserved., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The study was aimed to evaluate the influence of the vascular disease, atherosclerotic obliterans (AO), on the location and concentration of elements in the arterial wall and serum. Use of a modern method for studying element's concentration and distribution in samples of clinical material, i.e. laser ablation inductively coupled plasma mass spectrometry, is presented. Elements are not equally distributed between the inner (intima) and the outer (media + adventitia) layer of the arterial wall. Among the studied elements, calcium was found to have an unquestionable role in the calcification of the wall. Increased concentration of calcium found in the inner part of the atherosclerotic arterial wall and in the plaque, as compared to the control arterial wall samples, demonstrates the unquestionable role of this element in the calcification of the wall observed in AO. Applied chemometric methods were useful for demonstrating the differences in the element's concentration in blood serum and the arterial wall samples between AO and the control group.

Changes in the indices of microcirculation and lipid metabolism were assessed in the process of treatment of patients with obliterating atherosclerosis of the lower extremity vessels and in combination with ischemic heart disease, with the II degree of ischemia those who had undergone revascularizing operations. It was found that plasmapheresis followed by plasmosorbtion improved the state of peripheral blood flow and decreased the concentration of blood lipoproteins of both low and high density, not decreasing the atherogenicity coefficient, and less effective in combination with ischemic heart disease, which was due to low selectivity of the carbofibrilar sorbent.

Aim: Prostaglandin (PG) receptor agonists are frequently used for the pharmacological treatment of arteriosclerosis obliterans (ASO). In particular, the PG receptors EP2 and IP stimulate vasodilation and inhibit platelet aggregation, biological processes thought to be protective against ASO and important for physiological homeostasis. However it is uncertain whether EP2 and IP exist in diseased arteries, or what their distribution within the artery might be. In this study, we analyzed the distribution of these PG receptors in patients with severe ASO to determine the potential application of stimulation of these receptors as targets for pharmacological treatment., Methods: We collected segments of atherosclerotic femoral arteries during femoropopliteal bypass surgery and determined the expression levels of EP2 and IP receptors by western blotting. Immunofluorescence was used to observe receptor localization., Results: Findings of western blotting showed an increased Cox-2 expression in patients with ASO. The EP2 as well as IP receptors were each induced approximately 3-fold in comparison to normal samples. The expression of these receptors was increased in the intimal layer as well as the medial layer; their expression was also detectable within the atherosclerotic plaque., Conclusion: We observed induction of the PG receptors EP2 and IP in atherosclerotic femoral arteries in the arterial intima, medial layer, as well as the associated atherosclerotic plaque. These results suggest that receptor-selective PG agonists specifically target atherosclerotic arteries and therefore, may find potential application in the pharmacological management of patients with ASO.

Data of 410 male patients operated on account of atherosclerosis obliterans of lower limbs vessels. Biochemichal parameters of functional endothelium status of the arteriae after operative treatment are studied. Superoxide dismutase activity and nitric oxide level are registered before and 5 days after the operation. Statistically reliable changes of the biochemical parameters in dependence of methods of the operative treatment are determined.

The work was aimed at elucidating the role of the indices of the antioxidant system (AOS) of the blood and nitrogen oxide content in differential diagnosis of atherosclerosis obiiterans (AO) and thromboangiitis obiiterans (TO) of the lower extremities. Presented herein are the findings of examining a total of one hundred and thirteen 30-to-45-year-old patients (of these, 60 had TO and 53 had AO) with various level of occlusion (from the femoropoplietal segment to the aortoiliac zone) and the stage of chronic arterial insufficiency (CAI IIA-IV). The control group was composed of 30 apparently healthy age-matched male subjects. Besides the clinical, laboratory and special instrumental methods of study, we determined the parameters of the AOS of blood and the content of nitrogen oxide degradation products. It was determined that the directedness and pronouncedness of deviations in the parameters of the AOS and nitrogen oxide from the physiological norm depended on not only the aetiology of the disease involved, but on the degree of tissue hypoxia predetermined by the stage of CAI of the lower limbs. For differential diagnosis between AO and TO, the most informative should be considered the coefficient: SOD activity/catalase activity, index of peroxide-luminol-dependent chemiluminescence and the content of nitrogen oxide degradation products.

We examined the genetic status of human leucocyte antigens (HLA), human platelet alloantigens (HPA) and neutrophil-specific antigens (NA) in patients with type 2 diabetes mellitus and diabetic arteriosclerosis obliterans (ASO). To our knowledge, the present study is the first report showing the relationship among three genetic factors in type 2 diabetes mellitus and ASO patients. HLA typing was performed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. HPA-typing and NA-typing were by a PCR-sequence-specific primer method. The incidence of HLA-DRB1*1501 was found to be significant in type 2 diabetes and non-diabetic, particularly ASO-positive patients, compared to control subjects. There were no differences in NA1/NA2 between the control and diabetic or non-diabetic ASO groups. However, the frequency of NA2/NA2 in ASO-positive diabetes and non-diabetic ASO patients was significantly higher than controls. The a/b genotype of HPA-5a/5b was significantly lower in type 2 diabetes and non-diabetic ASO-positive patients than in controls. These findings suggest that genetic studies of HLA, NA and HPA could be useful to understand the pathogenesis of type 2 diabetes and ASO.

The aim of the present study was to investigate the possibility of phosphorus magnetic resonance spectroscopy (MR spectroscopy) in the diagnosis of metabolic lesions of skeletal musculature in patients with intermittent claudication syndrome, chronic cardiac failure, and varicose diseases of the lower limbs. Studies included 50 males: 20 patients with intermittent claudication, 10 patients with chronic cardiac failure, and 10 patients with varicose veins. The control group consisted of 10 healthy volunteers. The following measures were determined: the phosphocreatinine index, the intracellular pH in the gastrocnemius muscle, and the half-recovery time for the phosphocreatinine index. The phosphocreatinine index and the pH at rest did not differ between study groups. Isotonic exercise produced no change in the phosphocreatinine index in the control group; patients with intermittent claudication showed a 26.1% decrease, patients with chronic cardiac failure showed an 8% decrease, and patients with varicose veins showed a 25.6% decrease. The only group showing a significant decrease in pH during exercise was the group of patients with intermittent claudication. This group also showed an inverse correlation between the pressure index and the extent of the decrease in the phosphocreatinine index. Thus, MR spectroscopy provides a non-invasive diagnostic method for lesions of energy metabolism in skeletal musculature in patients with deranged peripheral hemodynamics.

The damage of the vascular endothelial cells is considered as the primary factor of the development of atherosclerotic changes. The damaged vascular endothelial cells secrete lower amounts of tissue plasminogen activator, antithrombin III, thrombomodulin, endothelium devived relaxing factor (EDRF) prostacycline (PGI2) and glycosaminoglycans. An increase of plasma viscosity and blood procoagulation activity is observed in the peripheral arterial obliterative disease as a result of the interaction between platelets, leucocytes and erythrocytes from the walls of the damaged vessels together with the impairment of blood fibrinolytic activity. It is considered that one of the factors responsible for the development of the atherosclerotic changes is chronic inflammation process of the vascular endothelium. This causes a considerable participation of inflammation cells, i.e. lymphocytes and monocytes in atherosclerosis development. It is observed that an increased level of tissue factor (TF) and factor VII produced as a result of their releasing by the activated monocytes in the atheromatous lamina rupture exerts procoagulation effect. The tissue factor inhibitor inhibits VIIa/TF/Xa complex activity.

Relationship between concentration of Mg and Cu in serum and the arterial wall was studied in patients with atherosclerosis obliterans (AO), aortic aneurysm (AA) and in the control group. The effect of ageing was also evaluated. The results showed increased serum concentration of Cu in the eldest control group (50-59 years) when compared to the younger (20-29 years). Serum concentration of Mg was decreased in AO and AA, and that in the arterial wall was lower in AA, than in controls. Concentration of Cu in serum and the arterial wall was higher in AO than in controls. Lower limb ischaemia results in decreased serum Mg and increased Cu in the critical degree as compared with the moderate degree of ischaemia. The ratio Mg/Cu was found lower both in serum and the arterial wall in AO and AA, as a result of ageing and vascular disease, and it could be better marker of ischaemia than individual element concentrations.

Unlabelled: The present study objective involved evaluation of possibilities of magnetic resonance spectroscopy with phosphorus (31P-MRS) in diagnosis of metabolic disorders of skeletal muscles in patients with intermittent claudication, chronic heart failure and varicose disease of the lower extremities. In 20 patients with intermittent claudication, 10 patients with chronic heart failure, 10 patients with varicose disease and 10 volunteers, 31P-MRS was performed with 1.5 T MR system (Magnetom SP 63, Siemens). The following parameters were computed: phosphorus-creatinine index, intracellular pH in calf muscle, and time of half-recovery of the phosphorus-creatinine index. At rest, the phosphorus-creatinine indexes were similar in all groups; pH values at rest did not vary either. During isotonic exercise the phosphorus-creatinine index in the control group remained uncharged. In patients with intermittent claudication, the phosphorus-creatinine index at peak of exercise was decreased by 26.1% (p < 0.001), in patients with varicose disease--by 25.6% (p < 0.001), in patients with chronic heart failure by 8% (p < 0.001). PCr recovery half-time was increased in all patients. The patient group with intermittent claudication showed a reverse correlation between the pressure index and the degree of phosphorus-creatinine index decrease., Conclusion: 31P-MRS makes it possible to carry out non-invasive diagnosis of energy metabolic disorders of skeletal muscles in patients with impaired peripheral hemodynamics.

The interrelation was studied of processes of lipid peroxidation (LPO), the antioxidant system (AOS) with the level of endogenous intoxication (EI) during treatment with olbetam. Before the treatments administered, significantly high levels were recordable of LPO, EI against the background of low AOS activity. An one-month course of treatment with olbetam was found to be effective in all the parameters studied (LPO, AOS, EI). One month after the withdrawal of the drug the olbetam action on the AOS activity plasma level of MDA is still observable, with the processes of LPO and EI tending to return to normal. The abovestated permits recommending olbetam in the treatment of atherosclerosis obliterans of arteries of the inferior limbs as a hypolipidemic drug preparation endowed with an antioxidant and deintoxicationg activities.

The relationships among concentrations of copper and zinc, the oxidase activity of ceruloplasmin (Cp) in serum, and Cu,Zn-SOD (superoxide dismutase) activity in erythrocytes were investigated in men with atherosclerosis obliterans (AO) and a control group. The oxidase activity of Cp was measured with o-dianisidine dihydrochloride as a substrate, and Cu,Zn-SOD activity in erythrocytes by using the RANSOD kit. The lipid profile and uric acid concentration were determined in AO and control groups. The results showed higher copper and zinc concentrations in serum in the AO group (20.0+/-3.5 and 18.0+/-3.2 micromol/L, respectively) in comparison with the control group (15.6+/-2.3 and 14.7+/-1.9 micromol/L). The Cp activity in serum was higher in the AO group (174.2+/-61.8 U/L) than in the control group (93.7+/-33.9 U/L), and a significant difference was found in the activity of Cu,Zn-SOD in erythrocytes (2389+/-1396 and 1245+/-365 U/g Hb, respectively) between both groups. The activity of Cu,Zn-SOD was positively correlated with copper in the control group (r=0.73), but not in AO, and negatively with uric acid concentration (r= -0.63) in the AO group. The oxidase activity of Cp was correlated with copper, but not zinc, in AO and control groups (r> or =0.65). Negative correlation coefficients were calculated for uric acid and copper and zinc concentrations in the AO group (-r > or = 0.61). Increased copper concentrations and oxidase activity of Cp in serum in AO and the activity of Cu,Zn-SOD in erythrocytes could result from atherosclerotic disease, accompanied by chronic ischemia of a lower limb. These results suggest also that relationship between copper concentration and Cu,Zn-SOD activity in erythrocytes found in the serum of healthy subjects may be disturbed in pathologic conditions.

Hepatocyte growth factor (HGF) exclusively stimulates the growth of endothelial cells without replication of vascular smooth muscle cells and acts as a survival factor against endothelial cell death. Therefore we hypothesized that a decrease in local vascular HGF might be related to the pathogenesis of peripheral arterial disease. We initially evaluated vascular HGF concentration in the vessels of patients with arteriosclerosis obliterans. Consistent with in vitro findings that hypoxia downregulated vascular HGF production, vascular HGF concentration in the diseased segments of vessels from patients with arteriosclerosis obliterans was significantly decreased as compared with disease-free segments from the same patients (P<0.05), accompanied by a marked reduction in HGF mRNA. On the other hand, a novel therapeutic strategy for ischemic diseases that uses angiogenic growth factors to expedite and/or augment collateral artery development has recently been proposed. Thus in view of the decreased endogenous vascular HGF, rhHGF (500 micrograms/animal) was intra-arterially administered through the internal iliac artery of rabbits in which the femoral artery was excised to induce unilateral hind limb ischemia, to evaluate the angiogenic activity of HGF, which could potentially have a beneficial effect in hypoxia. Administration of rhHGF twice on days 10 and 12 after surgery produced significant augmentation of collateral vessel development on day 30 in the ischemic model as assessed by angiography (P<0.01). Serial angiograms revealed progressive linear extension of collateral arteries from the origin stem artery to the distal point of the reconstituted parent vessel in HGF-treated animals. In addition, we examined the feasibility of intravenous administration of rhHGF in a moderate ischemia model. Importantly, intravenous administration of rhHGF also resulted in a significant increase in angiographic score as compared with vehicle (P<0.01). Overall, a decrease in vascular HGF might be related to the pathogenesis of peripheral arterial disease. In the presence of decreased endogenous HGF, administration of rhHGF induced therapeutic angiogenesis in the rabbit ischemic hind limb model, as potential cytokine supplement therapy for peripheral arterial disease.

Background: Endothelial prostacyclin production is modulated by blood flow (wall shear stress). Local plasma prostacyclin concentrations and hemodynamic parameters have therefore been investigated in patients with atherosclerosis obliterans before and after angioplasty. METHODS., Design: Prospective study., Setting: Department of Surgery, Matsuyama Red Cross Hospital, Matsuyama, Japan., Patients: Nine lower limbs in eight patients with significant stenoses of the iliac artery were studied., Interventions: blood samples were obtained from the femoral artery and femoral vein of nine lower limbs undergoing percutaneous balloon angioplasty of the iliac artery., Measures: Prostacyclin concentrations, radioimmunoassayed as 6-keto-prostaglandin F1 alpha, were measured before and after balloon dilatation. Femoral blood flow and the ankle-brachial pressure index (ABI) were measured using a Doppler velocimeter before and after the procedure. The femoral blood flow waveform was used to calculate the mean blood flow and shear stress variation., Results: Before angioplasty, the mean (+/- SEM) plasma prostacyclin concentration was 21.6 +/- 1.5 pg/ml in the femoral artery and 25.4 +/- 1.1 pg/ml in the femoral vein. After angioplasty, these values increased to 25.6 +/- 2.2 pg/ml (p < 0.05) and 32.8 +/- 1.8 pg/ml (p < 0.01), respectively. The pre-procedural ABI, mean flow rate, and shear stress variation were 0.596 +/- 0.071, 354.1 +/- 63.3 ml/min, and 69.1 +/- 9.9 dyne/cm2, respectively. Both ABI and shear stress variation increased after angioplasty to 0.738 +/- 0.076 (p < 0.05) and 111.1 +/- 24.2 (p = 0.0775) dyne/cm2, but the mean flow rate (287.1 +/- 61.1 ml/min after angioplasty) did not increase (p = 0.2002)., Conclusions: These results suggest that prostacyclin production increases after angioplasty, possibly due to increases in the intraluminal pressure and shear stress variation. This enhanced prostacyclin production may help to maintain arterial or bypass graft patency.

The authors have proposed a method for predicting the effect of Buchwald's operation (partial iliac bypass surgery) and successfully tested it in 32 patients with hyperlipidemia. The method is based on pharmacological simulation of major pathophysiological intervention points verified by radionuclide hepatobiliscintigraphy. Evaluating lipid metabolic changes before and after simulation serves as a basis for predicting the effect of the operation.

Purpose: Nitric oxide (NO) not only relaxes vascular smooth muscles, but it also reduces platelet adhesion and is itself a potent antiaggregatory substance. Experimental studies have shown that the release of NO is modulated by the blood flow. However, little clinical information is available about the effects of hemodynamic changes after arterial reconstruction on NO production. We therefore examined whether the plasma levels of nitrite (NO2-) and nitrate (NO3-) ions increased after arterial reconstruction in patients with arteriosclerosis obliterans (ASO)., Methods: Blood samples were obtained from the femoral artery in seven patients who underwent arterial reconstruction and seven healthy individuals (control). NO2- and NO3- levels were measured using high-performance liquid chromatography before the operation and 1 hour and 14 days after the operation. In addition, the mean femoral artery blood flow and ankle-brachial pressure index (ABI) were also measured using a duplex and Doppler velocimeter both before and after the operations., Results: In the control subjects, the mean plasma NO2-, NO3-, and NOx (NO2- plus NO3-) levels in the femoral artery were 0.37 +/- 0.15 mumol/L, 45.6 +/- 10.8 mumol/L, and 46.0 +/- 10.9 mumol/L, respectively. Before the operation in the patients with ASO, the mean plasma NO3- (23.8 +/- 2.2 mumol/L) and NOx levels (24.0 +/- 2.3 mumol/L) were significantly lower than those in the control subjects, whereas the plasma NO2- levels (0.27 +/- 0.04 mumol/L) were comparable between the two groups. At 14 days after operation, the mean plasma NO3- and NOx levels in the femoral artery were significantly increased to 42.8 +/- 5.6 mumol/L and 43.4 +/- 5.6 mumol/L compared with those before the operation, whereas the mean plasma NO2- levels (0.50 +/- 0.05 mumol/L) changed significantly. The mean ABI and the mean flow rate before the operation were 0.32 +/- 0.07 and 344 +/- 145 ml/min, respectively. Both the ABI and the mean flow rate significantly increased to 1.04 +/- 0.06 and 627 +/- 141 ml/min after the operation., Conclusions: In patients who have ASO, the mean plasma level of NO is significantly lower than that of healthy individuals. In patients with ASO, the mean blood flow increased significantly after arterial reconstruction. This hemodynamic improvement may thus enhance NO production and may also help to maintain the patency of the bypass graft or native artery.

In 95 patients with atherosclerotic occlusion of aorto-iliac and femoro-popliteal arterial segments and II-IV grade of ischemia (according to Fontaine) the concentration of malonic dialdehyde and general antioxidant activity of the blood plasma in ischemia period of time and in various terms of revascularization period were determined. The processes rising of peroxide clearance of lipids (PCL) in injured limb and lowering of antioxidant (AO) activity of blood plasma was discovered. In the revascularization period further significant activation of PCL processes (maximally during the first day) and gradual rising of AO activity of blood plasma (maximally on the 3-5th day) was revealed. The magnitude of these processes depended on the tissue ischemia extension and its severity.

The prevalence of abnormal lipid and lipoprotein values was determined in 125 consecutive patients with lower-extremity arteriosclerosis obliterans, and the lipid and lipoprotein abnormalities in these patients were characterized. Only 13% of the patients had normal lipid/lipoprotein profiles. Forty-eight percent of patients had low levels of high-density lipoprotein cholesterol. High-density lipoprotein cholesterol values were lower in patients with concomitant coronary heart disease compared with those without heart disease. High-density lipoprotein cholesterol values were inversely related to weight, to triglyceride values, and to diabetes mellitus. Twenty-eight percent of patients had "desirable" total cholesterol levels (< 200 mg/dL), and 32% had low-density lipoprotein cholesterol values less than 130 mg/dL. Following National Cholesterol Education Program guidelines may be misleading in patients with documented lower-extremity atherosclerosis; therefore, complete lipid/lipoprotein profiles should be performed in these patients.

A retrospective study of 112 patients with abdominal aortic aneurysm (AAA) and 232 with arteriosclerosis obliterans (ASO) demonstrated that 16.7% of those with AAA and 1.6% of those with ASO had a history of gastroduodenal ulcer; 83% of these lesions with AAA were gastric ulcers. Ulcer bleeding after vascular reconstruction developed in seven patients with AAA and one with ASO. Serum fibrinogen levels and platelet counts were significantly lower in patients with AAA than in those with ASO or controls. A prospective study showed that 25 (52.1%) of 48 patients with AAA and six (20.0%) of 30 patients with ASO had endoscopically proved gastroduodenal lesions before vascular reconstruction. None of them developed postoperative bleeding after treatment of both their gastroduodenal lesions and coagulopathy. Furthermore, the significant decrease in blood flow and prostaglandin content of gastric mucosa was demonstrated in patients with AAA.

To assess the diagnostic value of myoglobin between elective surgery and acute arterial occlusion, serum and urine myoglobin (S-Mb, U-Mb) levels were measured before and for 7 consecutive days following arterial reconstructive surgery in 7 patients with abdominal aortic aneurysm or arteriosclerosis obliterans (elective surgery group), and in 20 patients with acute arterial occlusion due to embolism or thrombosis. They were divided into three groups based on symptoms and other features: mild, moderate, and severe groups. S-Mb and U-Mb levels were normal before surgery with a maximum of 389 ng/ml and 1,670 ng/ml after surgery in the elective surgery group, and 489 ng/ml and 11.7 ng/ml before surgery with a maximum of 703 ng/ml and 294 ng/ml after surgery in the mild cases. These two groups showed no complications after surgery. In the moderate group, high values of 2,420 ng/ml and 25,300 ng/ml were noted before surgery, and these values were elevated to 14,900 ng/ml and 175,000 ng/ml after surgery with complications of acute renal failure or peripheral nerve paresis. In the severe group, the values were 9,440 ng/ml and 260,000 ng/ml before surgery, and 160,000 ng/ml and 1,300,000 ng/ml after surgery, the elevation being associated with the severe clinical complication, myonephropathic metabolic syndrome (MNMS). All patients in this group died of MNMS. S-Mb and U-Mb levels before surgery proved useful for predicting the prognosis of patients with acute arterial occlusion. The findings obtained in our canine studies on the mechanism and treatment of MNMS suggest that alpha-tocopherol, a free radical scavenger, may be effective for treating dreadful complications such as MNMS.

The study of some indices of external respiration through spirography, studies of acid-base status and oxygenation parameters of arterialized capillary blood, evaluation of tissue oxygen tension by means of polarography in 44 cases of chronic thromboobliterating disease of the extremities before and after therapy with 1.7--2.0 ata at 40 to 60 minutes exposure in single oxygen barochambers were carried out with the aim of investigation of alterations of gas exchange and tissue oxygen balance. It was found that in hyperbaric oxygenation the normalization of metabolic processes in an ischemic tissue takes place together with the elimination of oxygen deficit and deviations in acid-base status.

Complex examination of 72 patients with obliterating atherosclerosis and 10 patients with obliterating endarteritis was performed. All the patients were given autotransfusion of UV-irradiated blood as conservative treatment, preoperative preparation and postoperative management. The course of AUVIB was followed by a decrease of the lactic acid level, increase of functional properties of hemoglobin, activation of humoral immunity, change of the blood hemostatic potential to the side of hypocoagulation. The AUVIB treatment was most effective in patients at initial stages and those with peripheral forms of the disease.

We determined by comparison, in 30 patients with arteriosclerosis obliterans and in 10 normal peoples, 50-70 years aged, the values of some glycolipidic parameters (blood glucose, triglyceridemia, cholesterolemia, nephaemia, beta- and pre-beta-lipoproteinemia) and moreover the hormonal ones (IRI, GH, cortisolemia) at fast in the morning, during the whole day and during some blocking and stimulating tests. Patients with arteriosclerosis obliterans presented a significant alteration of the lipidic outline (hyper-lipoproteinemia of IV type sec. Fredr) and of the carbohydrate metabolism, emphasized at the OGTT by a dissimilar tolerance (normal, borderline and pre-diabetic type) referring to a normal high and low insulin immission respectively. We dissert widely about biohumural data, as reflexes involved from the pancreatic function and from the ischaemic process, and we report the eventual tie between the detected hormone-metabolic disorders and the development of arteriosclerotic occlusive disease in the lower extremities.

Six patients with advanced arteriosclerosis obliterans in the lower extremities were subjected to an exercise test on a tread mill with and without dipyridamole treatment. Prostacyclin (PGI2) release was measured by the concentration of its stable metabolite, 6-keto-prostaglandin F1 alpha in plasma. All the patients suffered from ischemic pain during both tests, but no changes were seen in plasma 6-keto-PGF1 alpha. Dipyridamole did not affect the physical performance. Our results suggest that atherosclerotic vessels do not increase PGI2 production in response to ischemia and that a single dose of dipyridamole does not change PGI2 production.

Measurements of oxygen tension in the lower extremity skin in patients with obliterating atherosclerosis has revealed the basal decrease of tissue oxygenation. Lumbar sympathectomy caused a temporary aggravation of regional hypoxia resulting from reflex responses to mechanical irritation of autonomic ganglions during operation. A preliminary injection of pentamine, blockade of lumbar ganglia with novocaine, sparing technique of ganglionectomy considerably reduced or even prevented hypoxic reaction of tissues. The efficiency of the operation is dependent on the degree of basal arterial ischemia, stage of the disease and technique of performing sympathectomy.