Explore the vast range of titles available.

The primary objective of this study was to compare the effects on muscle metabolism of two types of aerobic training, with and without a load on the lower limbs, in adults with peripheral arterial disease (PAD). A simple blind randomized clinical trial was conducted using two groups: conventional aerobic (CG) and modified aerobic with a load on the lower limbs (MG). Both groups underwent training by walking three times a week over a 12-week period. The ratings of muscle metabolism were determined after a treadmill test with constant velocity and inclination concomitant with the use of near infrared spectroscopy (NIRS). Altogether 40 individuals with PAD (CG = 65.45 ± 10.60 and MG = 63.10 ± 10.54) were included in the study. After the intervention, in both groups, there was a reduction in the relative time to recovery (p = 0.002), an improvement in the re-oxygenation rate (p = 0.017), an increased time of resistance after reaching the lowest muscle oxygen saturation (StO 2 ) (p < 0.001), an increase in the distance walked (p < 0.001), and an improvement of the walking economy relative to StO 2 (p < 0.001). After 12 weeks of training, an improvement in the deoxygenation rate was observed in both groups (p = 0.002), but with a greater magnitude in the CG (p = 0.017). Only the CG presented an increase in time to reach the lowest StO 2 on the treadmill after the intervention (p = 0.010). The traditional aerobic training was superior to the modified training in relation to the improvement of muscle metabolism in patients with PAD.

Background: The effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression, and new treatment methods are needed. In 2011, a plasmid VEGF65-gene therapy drug was approved in Russia for the treatment of chronic lower limb ischemia (ClinicalTrials.gov identifier: NCT03068585). The objective of this follow-up study was to evaluate the long-term safety and efficacy of gene therapy in patients with limb ischemia of atherosclerotic genesis. Aims: To evaluate the long-term safety and efficacy of the therapeutic angiogenesis, 36 patients in the treatment group (pl-VEGF165) and 12 patients in the control group participated in a 5-year follow-up study. Planned examinations were carried out annually for 5 years after pl-VEGF165 administration. Results: Differences in the frequency of major cardiovascular events (pl-VEGF165 5/36 versus control 2/12; p = 0.85), malignancies (pl-VEGF165 1/36 versus control 0/12; p = 0.38) and impaired vision (there was none in either group) over the 5-year follow-up period did not achieve statistical significance. The target limb salvage was 95% (n = 36) and 67% (n = 12) in the pl-VEGF165 and control groups, respectively. The pain-free walking distance value increased by 288% from 105.7 ± 16.5 m to 384 ± 39 m in the treatment group by the end of the fifth year, with a peak of 410.6 ± 86.1 m achieved by the end of the third year. The ankle-brachial index (ABI) increased from 0.47 ± 0.01 to 0.56 ± 0.02 by the end of the first year, with a subsequent slight decrease to 0.51 ± 0.02 by the fifth year. The maximum increment of transcutaneous oximetry test (tcoO2) by 36%, from 66.6 ± 3.7 mm Hg to 90.7 ± 4.9 mm Hg, was observed by the end of the second year. Conclusion: The therapeutic effect of angiogenesis induction by gene therapy persists for 5 years.

The aim of the study was to verify the effects of creatine (Cr) supplementation on functional capacity (walking capacity; primary outcome) and calf muscle oxygen saturation (StO2) (secondary outcome) in symptomatic peripheral arterial disease (PAD) patients. Twenty-nine patients, of both sexes, were randomized (1:1) in a double-blind manner for administration of placebo (PLA, n = 15) or creatine monohydrate (Cr, n = 14). The supplementation protocol consisted of 20 g/day for 1 week divided into four equal doses (loading phase), followed by single daily doses of 5 g in the subsequent 7 weeks (maintenance phase). Functional capacity (total walking distance) was assessed by the 6 min walk test, and calf muscle StO2 was assessed through near infrared spectroscopy. The measurements were collected before and after loading and after the maintenance phase. The level of significance was p < 0.05. No significant differences were found for function capacity (total walking distance (PLA: pre 389 ± 123 m vs. post loading 413 ± 131 m vs. post maintenance 382 ± 99 m; Cr: pre 373 ± 149 m vs. post loading 390 ± 115 m vs. post maintenance 369 ± 115 m, p = 0.170) and the calf muscle StO2 parameters (p > 0.05). Short- and long-term Cr supplementation does not influence functional capacity and calf muscle StO2 parameters in patients with symptomatic PAD.

Patients with peripheral artery disease (PAD) have reduced muscle capillary density. Walking training (WT) is recommended for PAD patients. The goal of the study was to verify whether WT promotes angiogenesis in PAD-affected muscle and to investigate the possible role of miRNA-126 and the vascular endothelium growth factor (VEGF) angiogenic pathways on this adaptation. Thirty-two men with PAD were randomly allocated to two groups: WT (n = 16, 2 sessions/week) and control (CO, n = 16). Maximal treadmill tests and gastrocnemius biopsies were performed at baseline and after 12 weeks. Histological and molecular analyses were performed by blinded researchers. Maximal walking capacity increased by 65% with WT. WT increased the gastrocnemius capillary-fiber ratio (WT = 109 ± 13 vs. 164 ± 21 and CO = 100 ± 8 vs. 106 ± 6%, p < 0.001). Muscular expression of miRNA-126 and VEGF increased with WT (WT = 101 ± 13 vs. 130 ± 5 and CO = 100 ± 14 vs. 77 ± 20%, p < 0.001; WT = 103 ± 28 vs. 153 ± 59 and CO = 100 ± 36 vs. 84 ± 41%, p = 0.001, respectively), while expression of PI3KR2 decreased (WT = 97 ± 23 vs. 75 ± 21 and CO = 100 ± 29 vs. 105 ± 39%, p = 0.021). WT promoted angiogenesis in the muscle affected by PAD, and miRNA-126 may have a role in this adaptation by inhibiting PI3KR2, enabling the progression of the VEGF signaling pathway.

The aims of this study were twofold: (1) to identify whether peripheral artery disease (PAD) patients had increased muscle concentration of angiogenic VEGF-A, anti-angiogenic VEGF165b or VEGF receptor 1 (VEGF-R1) when compared with control subjects, and (2) to evaluate whether exercise training in PAD patients was associated with changes in muscle concentration of VEGF-A, VEGF165b or VEGF-R1. At baseline, 22 PAD and 30 control subjects underwent gastrocnemius muscle biopsy. Twelve PAD patients were treated with supervised exercise training (SET) and underwent muscle biopsy after 3 weeks and 12 weeks of training and had sufficient tissue to measure VEGF-A, VEGF165b and VEGF-R1 concentrations in skeletal muscle lysates by ELISA. Muscle concentrations of VEGF-A and VEGF165b were similar in PAD patients versus controls at baseline. At both time points after the start of SET, VEGF-A levels decreased and there was a trend towards increased VEGF165b concentrations. At baseline, VEGF-R1 concentrations were lower in PAD patients when compared with controls but did not change after SET. Skeletal muscle concentrations of VEGF-A are not different in PAD patients when compared with controls at baseline. SET is associated with a significant reduction in VEGF-A levels and a trend towards increased VEGF165b levels. These somewhat unexpected findings suggest that further investigation into the mechanism of vascular responses to exercise training in PAD patients is warranted.

Patients with critical limb ischemia (CLI) have a high risk to develop cardiovascular events (CVE). We hypothesized that in CLI patients platelets would display increased baseline activation and reactivity. We investigated baseline platelet activation and platelet reactivity in patients with CLI. In this study baseline platelet activation and platelet reactivity in response to stimulation of all major platelet activation pathways were determined in 20 CLI patients (11 using aspirin and 9 using vitamin K-antagonists) included in the Juventas-trial (clinicaltrials.gov NCT00371371) and in 17 healthy controls. Platelet activation was quantified with flow cytometric measurement of platelet P-selectin expression and fibrinogen binding. CLI patients not using aspirin showed higher baseline platelet activation compared to healthy controls. Maximal reactivity to stimulation of the collagen and thrombin activation pathway was decreased in CLI patients compared to healthy controls. In line, attenuated platelet reactivity to stimulation of multiple activation pathways was associated with several traditional risk factors for cardiovascular disease. Baseline platelet activation was increased in CLI patients, whereas the reactivity of circulating platelets to several stimulatory agents is decreased. Reactivity of platelets was inversely correlated with cardiovascular risk factors.

Atherosclerotic peripheral artery disease (PAD) is common and results in limitations in quality of life and potential progression to limb loss. Options for therapy include medical therapy, supervised exercise, surgical revascularization, and, more recently, endovascular therapies to restore arterial perfusion to the limb. Endovascular revascularization has evolved over the past 2 decades, from percutaneous transluminal angioplasty (PTA) to self-expanding stents, atherectomy, laser angioplasty, and drug-eluting stents. Despite impressive technologic advances, PTA remains the standard of care at many institutions and is the recommended primary treatment modality for femoral-popliteal PAD according to current American College of Cardiology Foundation/American Heart Association guidelines. However, restenosis after PTA is common. Therefore, a significant clinical need remains for a device that is able to achieve more durable patency than PTA but does not require a permanent implant. Drug-coated balloons (DCBs) have the potential to address this need. Several randomized controlled clinical trials of PTA balloons coated with different formulations of paclitaxel have been conducted in Europe (N Engl J Med 2008;358:689-699) (Circulation 2008;118:1358-1365) (Circ Cardiovasc Interv 2012;5:831-840) (JACC Cardiovas Interv 2014;7:10-19) and demonstrated more durable efficacy than PTA with comparable safety. These studies were limited by small sample sizes and powered solely for an angiographic primary end point. The pivotal LEVANT 2 trial was designed in collaboration with the US Food and Drug Administration to demonstrate safety and efficacy in a large population and to obtain US Food and Drug Administration approval. A prospective, multicenter, single-blind trial comparing the Lutonix DCB (Bard Lutonix; New Hope, MN) versus PTA for treatment of femoropopliteal PAD (LEVANT 2) is the first US-based 2:1 randomized controlled trial of 476 patients with femoral-popliteal PAD designed to demonstrate superior efficacy and noninferior safety of a novel paclitaxel DCB compared with PTA. The primary efficacy end point is primary patency at 12 months. The primary safety end point is composite freedom at 12 months from perioperative death, index limb amputation, reintervention, and limb-related mortality. A series of important secondary end points include physical functioning, quality of life, revascularizations, and alternative measures of patency. To minimize bias potential for confounding variables, LEVANT 2 (1) excluded patients stented after predilation before randomization, (2) incorporated very stringent criteria for bailout stenting, (3) did not count bailout stenting as a target lesion revascularization or failure of any end point, (4) required a blinded clinician to perform clinical evaluations at follow-up, and (5) required clinical assessment before review of duplex ultrasound results. LEVANT 2 represents the first US-inclusive multicenter, randomized controlled trial to assess the safety and efficacy of a novel DCB compared with PTA as primary therapy for symptomatic PAD on the background of standard medical therapy.

IntroductionDiabetes mellitus is a well-defined risk factor for peripheral artery disease (PAD), but protects against the development and growth of abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial stiffening and peripheral arterial media sclerosis. Advanced glycation end-products (AGEs) are increased in diabetes mellitus and cardiovascular disease. AGEs are known to form cross-links between proteins and are associated with arterial stiffness. Whether AGEs contribute to the protective effects of diabetes mellitus in AAA is unknown. Therefore, the ARTERY (Advanced glycation end-pRoducts in patients with peripheral arTery disEase and abdominal aoRtic aneurYsm) study is designed to evaluate the role of AGEs in the diverging effects of diabetes mellitus on AAA and PAD.Methods and analysisThis cross-sectional multicentre study will compare the amount, type and location of AGEs in the arterial wall in a total of 120 patients with AAA or PAD with and without diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular parameters, including pulse wave velocity, will be measured to evaluate the association between arterial stiffness and AGEs. Finally, AGEs will be measured in serum, urine, and assessed in skin with skin autofluorescence using the AGE Reader.Ethics and disseminationThis study is approved by the Medical Ethics committees of University Medical Center Groningen, Martini Hospital and Medisch Spectrum Twente, the Netherlands. Study results will be disseminated through peer-reviewed journals and scientific events.Trial registration numbertrialregister.nl NTR 5363.

Nitrite stores decrease after exercise in patients with peripheral artery disease (PAD) and diabetes represents decreased nitric oxide (NO) bioavailability that may contribute to endothelial dysfunction and limit exercise duration. The primary objective of this placebo-controlled study was the safety and tolerability of multiple doses of oral sodium nitrite in patients with PAD, predominantly with diabetes, over a period of 10 weeks. The primary efficacy endpoint was endothelial flow-mediated dilatation (FMD) and secondary efficacy endpoints included a 6-minute walk test and quality of life assessment. Of the 55 subjects, the most common side effects attributed to sodium nitrite were a composite of headache and dizziness occurring in 21% with the 40 mg dose and 44% with the 80 mg dose. There was no clinically significant elevation of methemoglobin. FMD non-significantly worsened in the placebo and 40 mg groups, but was stable in the 80 mg group. Diabetic patients receiving 80 mg had significantly higher FMD compared with the placebo and 40 mg groups. There was no significant change in 6-minute walk test or quality of life parameters over time compared to placebo. In conclusion, sodium nitrite therapy is well tolerated in patients with PAD. The possible clinical benefit of sodium nitrite should be studied in a larger and fully powered trial.

We investigated if corilagin can ameliorate or reverse atherosclerotic development via the toll-like receptor 4 (TLR4) signaling pathway and . Ana-1 cells or mouse peritoneal macrophages (MPMs) were stimulated with oxidized low-density lipoprotein followed by corilagin treatment. TLR4 expression in Ana-1 cells was upregulated by lentiviral transduction and downregulated by small interfering RNA. Peripheral blood mononuclear cells (PBMCs), plasma samples, and femoral arteries were collected from rats exhibiting peripheral artery disease (PAD). mRNA and protein expression of TLR4 and downstream molecules were decreased significantly by corilagin treatment in Ana-1 cells, MPMs, and rat PBMCs, and the reduction remained irrespective of downregulation or upregulation of TLR4 expression in Ana-1 cells. Corilagin also exerted a prominent effect on changes in plasma levels of cytokines and the pathologic manifestation of atherosclerosis in femoral arteries. Corilagin could ameliorate the development of atherosclerotic plaques by inhibiting the TLR4 signaling pathway in monocyte/macrophages and reduce the release of proinflammatory cytokines. This study provides a new therapeutic target and new targeting drug to oppose atherosclerosis and reveals the enormous potential of corilagin for control of PAD in humans.