Retained Functionality of Atherosclerotic Human Arteries Following Photoactivated Linking of the Extracellular Matrix by Natural Vascular Scaffolding Treatment.

In this study, we investigated natural vascular scaffolding (NVS) treatment on vascular functionality using freshly isolated human popliteal arteries in vitro. Arteries were exposed to intraluminal NVS treatment consisting of a compound (4 amino-1,8-naphthalimide) photoactivated by a 450-nm light-emitting light fiber placed inside the artery. This procedure results in covalent linking between the extracellular matrix proteins to achieve a larger vessel diameter post-angioplasty and minimizing elastic recoil. Immediately following NVS treatment, rings were cut from the treated arteries and mounted in organ baths for contractility testing in response to U46619 and sodium nitroprusside. We also investigated the effect of NVS treatment on IL-6 cytokine release from vascular rings following a 4-h organoculture post-NVS treatment. Based on our results, we conclude that exposure of the vessels to NVS treatment does not adversely affect the contractile responsiveness of the vascular smooth muscle and exerts no pro-inflammatory effect. Graphical abstract.

Lineage tracing reveals evidence of a popliteal lymphatic muscle progenitor cell that is distinct from skeletal and vascular muscle progenitors.

Loss of popliteal lymphatic vessel (PLV) contractions, which is associated with damage to lymphatic muscle cells (LMCs), is a biomarker of disease progression in mice with inflammatory arthritis. Currently, the nature of LMC progenitors has yet to be formally described. Thus, we aimed to characterize the progenitors of PLV-LMCs during murine development, towards rational therapies that target their proliferation, recruitment, and differentiation onto PLVs. Since LMCs have been described as a hybrid phenotype of striated and vascular smooth muscle cells (VSMCs), we performed lineage tracing studies in mice to further clarify this enigma by investigating LMC progenitor contribution to PLVs in neonatal mice. PLVs from Cre-tdTomato reporter mice specific for progenitors of skeletal myocytes (Pax7+ and MyoD+) and VSMCs (Prrx1+ and NG2+) were analyzed via whole mount immunofluorescent microscopy. The results showed that PLV-LMCs do not derive from skeletal muscle progenitors. Rather, PLV-LMCs originate from Pax7-/MyoD-/Prrx1+/NG2+ progenitors similar to VSMCs prior to postnatal day 10 (P10), and from a previously unknown Pax7-/MyoD-/Prrx1+/NG2- muscle progenitor pathway during development after P10. Future studies of these LMC progenitors during maintenance and repair of PLVs, along with their function in other lymphatic beds, are warranted.

Acute mitochondrial antioxidant intake improves endothelial function, antioxidant enzyme activity, and exercise tolerance in patients with peripheral artery disease.

Peripheral artery disease (PAD) is a manifestation of atherosclerosis in the leg arteries, which causes claudication. This may be in part due to vascular mitochondrial dysfunction and excessive reactive oxygen species (ROS) production. A mitochondrial-targeted antioxidant (MitoQ) has been shown to improve vascular mitochondrial function that, in turn, led to improved vascular function in older adults and animal models. However, the roles of vascular mitochondria in vascular function including endothelial function and arterial stiffness in patients with PAD are unknown; therefore, with the use of acute MitoQ intake, this study examined the roles of vascular mitochondria in endothelial function, arterial stiffness, exercise tolerance, and skeletal muscle function in patients with PAD. Eleven patients with PAD received either MitoQ or placebo in a randomized crossover design. At each visit, blood samples, brachial and popliteal artery flow-mediated dilation (FMD), peripheral and central pulse-wave velocity (PWV), blood pressure (BP), maximal walking capacity, time to claudication (COT), and oxygen utility capacity were measured pre- and-post-MitoQ and placebo. There were significant group by time interactions (P < 0.05) for brachial and popliteal FMD that both increased by Δ2.6 and Δ3.3%, respectively, and increases superoxide dismutase (Δ0.03 U/mL), maximal walking time (Δ73.8 s), maximal walking distance (Δ49.3 m), and COT (Δ44.2 s). There were no changes in resting heart rate, BP, malondialdehyde, total antioxidant capacity, PWV, or oxygen utility capacity (P > 0.05). MitoQ intake may be an effective strategy for targeting the vascular mitochondrial environment, which may be useful for restoring endothelial function, leg pain, and walking time in patients with PAD.NEW & NOTEWORTHY The results of this study reveal for the first time that acute oral intake of mitochondrial-targeted antioxidant (MitoQ, 80 mg) is effective for improving vascular endothelial function and superoxide dismutase in patients with peripheral artery disease (PAD). Acute MitoQ intake is also effective for improving maximal walking capacity and delaying the onset of claudication in patients with PAD. These findings suggest that the acute oral intake of MitoQ-mediated improvements in vascular mitochondria play a pivotal role for improving endothelial function, the redox environment, and skeletal muscle performance in PAD.

Adult Human Vein Grafts Retain Plasticity of Vessel Identity.

BACKGROUND: The spiral saphenous vein graft is an excellent choice for venous reconstruction after periphery vein injury, but only few cases have been reported. We implanted a segment of a single saphenous vein into both the popliteal vein as a venous vein graft and into the popliteal artery as an arterial vein graft at the same time in a trauma patient; we then had an extraordinary opportunity to harvest and examine both patent venous and arterial vein grafts at 2 weeks after implantation. METHODS: A spiral saphenous vein graft was made as previously described and implanted into the popliteal vein and artery as interposition grafts; because of the patient's serious injuries, an amputation was performed at day 18 after vascular reconstruction. The grafts were harvested, fixed, and examined using histology and immunohistochemistry. RESULTS: Both grafts were patent, and there was a larger neointimal area in the venous graft compared to the arterial graft. There were CD31- and vWF-positive cells on both neointimal endothelia, with subendothelial deposition of α-actin-, CD3-, CD45-, and CD68-positive cells. There were fewer cells in the venous graft neointima compared to the arterial graft neointima; however, there were more inflammatory cells in the neointima of the venous graft. Some of the neointimal cells were PCNA-positive, whereas very few cells were cleaved caspase-3 positive. The venous graft neointimal endothelial cells were Eph-B4 and COUP-TFII positive, while the arterial graft neointimal endothelial cells were dll-4 and Ephrin-B2 positive. CONCLUSIONS: The spiral saphenous vein graft remains a reasonable choice for vessel reconstruction, especially in the presence of diameter mismatch. Both the venous and arterial grafts showed similar re-endothelialization and cellular deposition; the venous graft had more neointimal hyperplasia and inflammation. At an early time, endothelial cells showed venous identity in the venous graft, whereas endothelial cells showed arterial identity in the arterial graft. CLINICAL RELEVANCE: Veins can be used as venous or arterial vein grafts but venous grafts have more neointimal hyperplasia and inflammation; vein grafts acquire different vessel identity depending on the environment into which they are implanted.

Morphological and pharmacological characterization of the porcine popliteal artery: A novel model for study of lower limb arterial disease.

OBJECTIVE: This study was undertaken to characterize structural and pharmacological properties of the pig popliteal artery in order to develop a novel system for the examination of lower limb blood flow regulation in a variety of cardiovascular pathologies, such as diabetes-induced peripheral artery disease. METHODS: Popliteal arteries were isolated from streptozocin-induced diabetic pigs or age-matched saline-injected control pigs for morphological study using transmission electron microscopy and for examination of vasoreactivity to pharmacological agents using wire myography. RESULTS: Transmission electron microscopy of the porcine popliteal artery wall revealed the presence of endothelial cell-smooth muscle cell interactions (myoendothelial junctions) and smooth muscle cell-smooth muscle cell interactions, for which we have coined the term "myo-myo junctions." These myo-myo junctions were shown to feature plaques indicative of connexin expression. Further, the pig popliteal artery was highly responsive to a variety of vasoconstrictors including norepinephrine, phenylephrine, and U46619, and vasodilators including acetylcholine, adenosine 5'-[ß-thio] diphosphate, and bradykinin. Finally, 2 weeks after streptozocin-induced diabetes, the normalized vasoconstriction of the pig popliteal artery to norepinephrine was unaltered compared to control. CONCLUSIONS: The pig popliteal artery displays structural and pharmacological properties that might prove useful in future studies of diabetes-associated peripheral artery disease and other lower limb cardiovascular diseases.

Biologic Drug Effect and Particulate Embolization of Drug-Eluting Stents versus Drug-Coated Balloons in Healthy Swine Femoropopliteal Arteries.

PURPOSE: To compare the drug effect in treated vessels and downstream effects in distal skeletal muscle of drug-coated balloons (DCBs) and drug-eluting stents (DESs) in a healthy preclinical swine model. MATERIALS AND METHODS: Four groups of treated iliofemoral arteries (percutaneous transluminal angioplasty [PTA]+DES, DCB+DES, DCB+bare metal stent [BMS], and DCB alone) of 12 healthy swine were assessed, with euthanasia at 30 days. Biological drug effect was evaluated using smooth muscle cell (SMC) loss score according to both depth and circumference as well as a neointimal fibrin and medial proteoglycan scores which were compared between the 4 groups. Vascular and skeletal muscle changes in regions downstream from the treated site were also assessed histologically for evidence of emboli. RESULTS: DESs showed greater medial SMC loss in the treated arteries irrespective of preceding DCB or PTA treatment in terms of depth (DCB+DES vs PTA+DES vs DCB+BMS vs DCB alone; median, 4.0 mm vs 3.8 mm vs 3.0 mm vs 2.2 mm; P = .009) and circumference (4.0 mm vs 3.5 mm vs 2.0 mm vs 1.2 mm, respectively; P = .007). Sections of skeletal muscles downstream from the treated arteries showed arteriolar changes of fibrinoid necrosis consistent with paclitaxel effect exclusively in the DCB groups (DCB+BMS, 26.9% of sections; DCB+DES, 14.3%; DCB alone, 19.2%; PTA+DES, 0%; P = .02). CONCLUSIONS: In the treated arteries, irrespective of preceding DCB treatment or PTA, DES treatment showed maximum drug effects vs DCB alone or in combination with BMS placement, and there was no detrimental toxic effect in DCB-treated iliofemoral arteries before DES treatment compared with PTA before DES treatment. Downstream vascular changes were exclusively seen in groups treated with DCBs.

Adventitial adipogenic degeneration is an unidentified contributor to aortic wall weakening in the abdominal aortic aneurysm.

OBJECTIVE: The processes driving human abdominal aortic aneurysm (AAA) progression are not fully understood. Although antiinflammatory and proteolytic strategies effectively quench aneurysm progression in preclinical models, so far all clinical interventions failed. These observations hint at an incomplete understanding of the processes involved in AAA progression and rupture. Interestingly, strong clinical and molecular associations exist between popliteal artery aneurysms (PAAs) and AAAs; however, PAAs have an extremely low propensity to rupture. We thus reasoned that differences between these aneurysms may provide clues toward (auxiliary) processes involved in AAA-related wall debilitation. A better understanding of the pathophysiologic processes driving AAA growth can contribute to pharmaceutical treatments in the future. METHODS: Aneurysmal wall samples were collected during open elective and emergency repair. Control perirenal aorta was obtained during kidney transplantation, and reference popliteal tissue obtained from the anatomy department. This study incorporates various techniques including (immuno)histochemistry, Western Blot, quantitative polymerase chain reaction, microarray, and cell culture. RESULTS: Histologic evaluation of AAAs, PAAs, and control aorta shows extensive medial (PAA) and transmural fibrosis (AAA), and reveals abundant adventitial adipocytes aggregates as an exclusive phenomenon of AAAs (P < .001). Quantitative polymerase chain reaction, immunohistochemistry, Western blotting, and microarray analysis showed enrichment of adipogenic mediators (C/EBP family P = .027; KLF5 P < .000; and peroxisome proliferator activated receptor-γ, P = .032) in AAA tissue. In vitro differentiation tests indicated a sharply increased adipogenic potential of AAA adventitial mesenchymal cells (P < .0001). Observed enrichment of adipocyte-related genes and pathways in ruptured AAA (P < .0003) supports an association between the extent of fatty degeneration and rupture. CONCLUSIONS: This translational study identifies extensive adventitial fatty degeneration as an ignored and distinctive feature of AAA disease. Enrichment of adipocyte genesis and adipocyte-related genes in ruptured AAA point to an association between the extent of fatty degeneration and rupture. This observation may (partly) explain the failure of medical therapy and could provide a lead for pharmaceutical alleviation of AAA progression.

Galectin-3 in Peripheral Artery Disease. Relationships with Markers of Oxidative Stress and Inflammation.

Galectin-3 is a modulator of oxidative stress, inflammation, and fibrogenesis involved in the pathogenesis of vascular diseases. The present study sought to characterize, in patients with peripheral artery disease (PAD), the localization of galectin-3 in arterial tissue, and to analyze the relationships between the circulating levels of galectin-3 and oxidative stress and inflammation. It also sought to compare the diagnostic accuracy of galectin-3 with that of other biochemical markers of this disease. We analyzed femoral or popliteal arteries from 50 PAD patients, and four control arteries. Plasma from 86 patients was compared with that from 72 control subjects. We observed differences in the expression of galectin-3 in normal arteries, and arteries from patients with PAD, with a displacement of the expression from the adventitia to the media, and the intima. In addition, plasma galectin-3 concentration was increased in PAD patients, and correlated with serologic markers of oxidative stress (F2-isoprostanes), and inflammation [chemokine (C-C motif) ligand 2, C-reactive protein, ß-2-microglobulin]. We conclude that the determination of galectin-3 has good diagnostic accuracy in the assessment of PAD and compares well with other analytical parameters currently in use.

Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction.

Endothelin-1 (ET-1), a potent vasoconstrictor secreted by vascular endothelial cells, has been implicated in the pathophysiology of numerous cardiovascular diseases, yet the direct impact of ET-1 on vascular function remains unclear. Therefore, in seven young (23 ± 1 yr) healthy subjects, we investigated the effect of an intra-arterial infusion of ET-1 on reactive hyperemia (RH) and flow-mediated dilation (FMD) in the popliteal artery following 5 min of suprasystolic cuff occlusion. ET-1 infusion significantly attenuated basal leg blood flow (control: 62 ± 4 ml/min, ET-1: 47 ± 9 ml/min), RH [area-under-curve (AUC); control: 162 ± 15 ml, ET-1: 104 ± 16 ml], and peak RH (control: 572 ± 51 ml/min, ET-1: 412 ± 32 ml/min) (P < 0.05). Administration of ET-1 also reduced FMD (control: 2.4 ± 0.3%, ET-1: 0.5 ± 0.5%) and FMD normalized for shear rate (control: 10.5 × 10-4 ± 2.0 × 10-4%/s-1, ET-1: 0.9 × 10-4 ± 2.8 ×10-4%/s-1). These findings reveal that elevated levels of ET-1 have a significant impact on vascular function, indicating that studies employing RH and FMD as markers of microvascular function and nitric oxide bioavailability, respectively, should exercise caution, as ET-1 can impact these assessments by tipping the balance between vasodilation and vasoconstriction, in favor of the latter.NEW & NOTEWORTHY Endothelin-1 (ET-1) is recognized as the body's most potent endogenous vasoconstrictor, but the impact of this peptide on vascular function is not well understood. The present study revealed that the intra-arterial administration of ET-1 impaired both microvascular and conduit vessel function of the leg in young, healthy, humans. Studies employing vascular testing in patient cohorts that experience a disease-related increase in ET-1 should thus exercise caution, as ET-1 clearly impairs vascular function.

Intrahistoria del síndrome de atrapamiento de la arteria poplítea. Un estudiante llamado T.P. Anderson Stuart / Internal history of popliteal artery entrapment syndrome. A student named

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The expression profile of angiogenic genes in critical limb ischemia popliteal arteries.

Critical limb ischemia (CLI) represents the most severe form of peripheral arterial disease (PAD) and is the leading cause of non-traumatic amputations in western populations. In recent years, therapeutic angiogenesis has been considered to be a potential treatment option for CLI patients, however the molecular mechanism of ischemia-induced vascularization is still not fully understood. The identification of genetic factors underlying vascular responses to ischemia will improve our understanding of the biological causes of the disease and enhance personalized therapies in the future. In this work, we determined, for the first time, the expression profile of angiogenesis-related genes utilizing unique human material: the popliteal arteries retrieved during lower limb amputation from patients with CLI. Using custom-designed TaqMan Low-Density Array (TLDA) cards we investigated the mRNA level of 90 genes on CLI samples compared to healthy donors. We identified three significantly up-regulated genes in CLI group: matrix metalloproteinase 9 (MMP-9), VE-cadherin (CDH5) and integrin alpha 4 (ITGA4). However, among all investigated genes, only lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) was significantly reduced. In order to verify whether hypoxic conditions occur in popliteal arteries of CLI patients, we validated the transcription level of selected proangiogenic genes by real-time PCR on a larger number of samples. These results showed that the expression of key genes involved in angiogenesis, such as MMP9, HGF, HIF1A, VEGF-A and FLT1 were elevated in patients with CLI. Moreover, the study revealed that the expression of VEGF-A and FLT1 was associated with activation of HIF1A transcription. In conclusion, our data revealed the alteration in the mRNA level of genes involved in matrix remodelling, cell-cell adhesion as well as endothelial cell migration and proliferation in human popliteal arteries.

Bacteria of leg atheromatous arteries responsible for inflammation.

BACKGROUND: Ischaemia of the lower limbs is frequently followed by inflammation and, in advanced cases, necrosis of peripheral tissues. Whether this is caused by arterial hypoperfusion only or by the presence of bacteria in the arterial walI as well remains unclear. The aim of the study was to prove the presence and source of bacteria in arterial specimens and evaluate their chemotactic properties resulting in the formation of periarterial cellular infiltrates. MATERIALS AND METHODS: Bacterial culture and testing for 16sRNA were performed in fragments of popliteal artery harvested from amputated limbs. Carotid artery plaques served as controls. Fragments of arteries were transplanted into scid mice to evaluate their chemotactic activity for macrophages. RESULTS: a) higher prevalence of isolates and 16sRNA in atherosclerotic popliteal than carotid arteries, b) high density of plaque and periarterial infiltrates and mRNA level for pro-inflammatory cytokines in popliteal arteries, c) prevalent microbes were Staphylococcus aureus, S. epidermidis and Enterococci, d) foot skin and arterial bacterial phenotypes and DNA revealed evident similarities, and e) more intensive mouse macrophage accumulation in popliteal than carotid implants into scid mice. CONCLUSIONS: The presence of bacteria in the lower limb arterial wall was documented. They may predispose to inflammation secondary to ischaemic changes.

Repeatability of vascular responsiveness measures derived from near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS)-derived measures of tissue oxygen saturation (StO2) have been recently shown to significantly correlate with the widely used method for noninvasively assessing vascular endothelial function, flow-mediated dilation (FMD). The purpose of this study was to examine the intraday and interday reliability of the reperfusion slope of StO2 (slope 2 StO2) and compare it to FMD Ultrasound-derived FMD was quantified following 5 min of distal cuff occlusion of the popliteal artery in nine healthy young men (26 ± 3 years). An FMD test was performed each of 4 days, with a fifth involving three tests. FMD was calculated as the greatest percent change in diameter from baseline (%FMD). StO2 was measured using NIRS throughout each test, with slope 2 StO2 being calculated as the upslope of 10-sec following cuff release. Reliability was determined using repeatability, intraclass correlation coefficients (ICC), and coefficient of variation (CV). Repeatability of slope 2 StO2 was better than %FMD for both intraday (0.43 and 5.65, respectively) and interday (0.48 and 4.82, respectively) comparisons; approximately 30% of mean values for slope 2 StO2 could be attributed to measurement error, whereas 100% of mean FMD could be for both intraday and interday comparisons. Similarly, ICC and CV values indicated stronger reliability of slope 2 StO2 compared to %FMD for both intraday (ICC 0.92 and 0.36, respectively; CV 9 ± 4% and 44 ± 24%, respectively) and interday (ICC 0.94 and 0.25, respectively; CV 14 ± 5% and 40 ± 22%, respectively) comparisons. In conclusion, NIRS-derived slope 2 StO2 can be used as a reliable measure of vascular reactivity.

Effects of meal ingestion on blood pressure and regional hemodynamic responses after exercise.

This study investigated the combined effects of consuming a meal during postexercise hypotension (PEH) on hemodynamics. Nine healthy young male subjects performed each of three trials in random order: 1) cycling at 50% of heart rate reserve for 60 min, 2) oral ingestion of a carbohydrate liquid meal (75 g glucose), or 3) carbohydrate ingestion at 40 min after cycling exercise. Blood pressure, heart rate, cardiac output, and blood flow in the superior mesenteric (SMA), brachial, and popliteal arteries were measured continuously before and after each trial. Regional vascular conductance (VC) was calculated as blood flow/mean arterial pressure. Blood pressure decreased relative to baseline values (P < 0.05) after exercise cessation. Blood flow and VC in the calf and arm increased after exercise, whereas blood flow and VC in the SMA did not. Blood pressure did not change after meal ingestion; however, blood flow and VC significantly decreased in the brachial and popliteal arteries and increased in the SMA for 120 min after the meal (P < 0.05). When the meal was ingested during PEH, blood pressure decreased below PEH levels and remained decreased for 40 min before returning to postexercise levels. The sustained increase in blood flow and VC in the limbs after exercise was reduced to baseline resting levels immediately after the meal, postprandial cardiac output was unchanged by the increased blood flow in the SMA, and total VC and SMA VC increased. Healthy young subjects can suppress severe hypotension by vasoconstriction of the limbs even when carbohydrate is ingested during PEH.

Aneurysm miRNA Signature Differs, Depending on Disease Localization and Morphology.

Limited comprehension of aneurysm pathology has led to inconclusive results from clinical trials. miRNAs are key regulators of post-translational gene modification and are useful tools in elucidating key features of aneurysm pathogenesis in distinct entities of abdominal and popliteal aneurysms. Here, surgically harvested specimens from 19 abdominal aortic aneurysm (AAA) and 8 popliteal artery aneurysm (PAA) patients were analyzed for miRNA expression and histologically classified regarding extracellular matrix (ECM) remodeling and inflammation. DIANA-based computational target prediction and pathway enrichment analysis verified our results, as well as previous ones. miRNA-362, -19b-1, -194, -769, -21 and -550 were significantly down-regulated in AAA samples depending on degree of inflammation. Similar or inverse regulation was found for miR-769, 19b-1 and miR-550, -21, whereas miR-194 and -362 were unaltered in PAA. In situ hybridization verified higher expression of miR-550 and -21 in PAA compared to AAA and computational analysis for target genes and pathway enrichment affirmed signal transduction, cell-cell-interaction and cell degradation pathways, in line with previous results. Despite the vague role of miRNAs for potential diagnostic and treatment purposes, the number of candidates from tissue signature studies is increasing. Tissue morphology influences subsequent research, yet comparison of distinct entities of aneurysm disease can unravel core pathways.

Vascular responsiveness determined by near-infrared spectroscopy measures of oxygen saturation.

Vascular impairments at the macro- and microcirculatory levels are associated with increased risk for cardiovascular disease. Flow-mediated dilation (FMD) is currently the most widely used method for non-invasive assessment of vascular endothelial function. Recently, near-infrared spectroscopy (NIRS)-derived measures of tissue oxygen saturation (StO2) have been used to characterize the dynamic response of local tissue perfusion to a brief period of ischaemia. The purpose of the present study was to establish correlations between the reperfusion rate of StO2 and FMD. Ultrasound-derived FMD was quantified after 5 min of distal cuff occlusion of the popliteal artery in 20 healthy young men (26 ± 3 years old). Triplicate measurements of end-diastolic arterial diameter were made every 15 s after cuff release, and FMD response was calculated as the greatest percentage change in diameter from baseline (%FMD). The StO2 was measured using NIRS throughout the duration of each test. Two consecutive FMD tests were performed, separated by 30 min of rest, and were averaged for %FMD and StO2. The %FMD was significantly correlated with the reperfusion slope of StO2 after cuff release (slope 2 StO2; r = 0.63, P = 0.003). In conclusion, the present study established a correlation between slope 2 StO2 and %FMD in healthy young men. These data suggest that NIRS-derived slope 2 StO2 can be used as a measure of vascular endothelial function.

Exclusión endovascular de aneurisma poplíteo roto / Endovascular exclusion of a ruptured politeal aneurysm

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Antioxidized LDL antibodies are associated with different metabolic pathways in patients with atherosclerotic plaque and type 2 diabetes.

OBJECTIVE: Oxidized lipoproteins and antioxidized LDL antibodies (antioxLDL abs) have been detected in human plasma and atherosclerotic lesions. The principle aim of this study was to analyze the possible relationship between IgG and IgM antioxLDL abs and factors involved in different metabolic pathways (inflammation, lipid metabolism, apoptosis, and cell cycle arrest profile) in the occluded popliteal artery (OPA) compared with the femoral vein (FV). RESEARCH DESIGN AND METHODS: Fifteen patients with advanced atherosclerosis and type 2 diabetes undergoing lower limb amputation participated in this study. Each patient had OPA and FV biopsy specimens and peripheral arterial occlusive disease. By real-time PCR, gene expression was analyzed from the OPA and FV specimens, and antioxLDL ab levels were measured by specific enzyme-linked immunosorbent assay. RESULTS: The OPA and FV showed a positive correlation between only IgM antioxLDL ab levels and the expression of genes involved in different metabolic pathways, including inflammation (TFPI), apoptosis (BAX, caspase 3, AKT1), plaque disruption (MMP2 and MMP10), lipid metabolism (SCARB1, PPARg), and cell turnover (CDKN1A), and genes for transcription and growth factors (NFkB and VEGFA, respectively). CONCLUSIONS: The results show that gene expression in the metabolic pathways (apoptosis, lipid metabolism, and inflammation) in the OPA and FV are directly related to the levels of IgM antioxLDL abs.

[Inflammation of the vascular wall and hyperhomocysteinemia in patients with atherosclerosis obliterans of lower limb arteries].

Presented herein are the findings of examination of 176 people. Of these, 128 were found to suffer lower limb atherosclerosis (LLA) and 48 were apparently healthy people constituting a control group. Amongst the 128 patients, 74 (58%) had atherosclerotic lesions of the iliac arteries, 54 (42%) subjects had lesions of the femoral and popliteal arteries. The average age of the patients amounted to 62.4±4.3 years. There were ten (8%) women and 118 (92%) men. The control group consisted of 42 (89%) men and six (11%) women. The mean age of the control group patients was 58.9±3.2 years. All underwent functional and laboratory examinations including angiography, duplex scanning and dopplerography of lower limb arteries, as well as determining blood serum markers of inflammation (hs-CRP and IL-6), as well as endothelial lesion markers (ET-1 and VWF). The comparative analysis revealed that patients with LLA had signs of chronic vascular inflammation accompanied in the majority of cases by hyperhomocysteinemia with endothelial dysfunction, as well as direct association between the degree of the vascular inflammatory reaction and severity of clinical manifestations of lower limb ischaemia.

Acute impact of intermittent pneumatic leg compression frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression in humans.

The mechanisms by which intermittent pneumatic leg compression (IPC) treatment effectively treats symptoms associated with peripheral artery disease remain speculative. With the aim of gaining mechanistic insight into IPC treatment, the purpose of this study was to investigate the effect of IPC frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression. In this two study investigation, healthy male subjects underwent an hour of either high-frequency (HF; 2-s inflation/3-s deflation) or low-frequency (LF; 4-s inflation/16-s deflation) IPC treatment of the foot and calf. In study 1 (n = 11; 23.5 ± 4.7 yr), subjects underwent both HF and LF treatment on separate days. Doppler/ultrasonography was used to measure popliteal artery diameter and blood velocity at baseline and during IPC treatment. Flow-mediated dilation (FMD) and peak reactive hyperemia blood flow (RHBF) were determined before and after IPC treatment. In study 2 (n = 19; 22.0 ± 4.6 yr), skeletal muscle biopsies were taken from the lateral gastrocnemius of the treated and control limb at baseline and at 30- and 150-min posttreatment. Quantitative PCR was used to assess mRNA concentrations of genes associated with inflammation and vascular remodeling. No treatment effect on vascular function was observed. Cuff deflation resulted in increased blood flow (BF) and shear rate (SR) in both treatments at the onset of treatment compared with baseline (P < 0.01). BF and SR significantly diminished by 45 min of HF treatment only (P < 0.01). Both treatments reduced BF and SR and elevated oscillatory shear index compared with baseline (P < 0.01) during cuff inflation. IPC decreased the mRNA expression of cysteine-rich protein 61 from baseline and controls (P <0 .01) and connective tissue growth factor from baseline (P < 0.05) in a frequency-dependent manner. In conclusion, a single session of IPC acutely impacts limb hemodynamics and skeletal muscle gene expression in a frequency-dependent manner but does not impact vascular function.