Editorial
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Open Access Editorial
The Need for Translational Research to Advance Peripheral Avenue Disease Management
Viewed by 2077
Abstract
Peripheral avenue affliction (PAD) is a wide term encompassing a range of atherosclerotic and aneurysmal conditions of the extra-coronary arteries [ane]. [...] Total commodity
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Open up Access Article
Correlation between Patient-Reported Symptoms and Ankle-Brachial Alphabetize after Revascularization for Peripheral Arterial Disease
Cited by xi | Viewed by 2668
Abstruse
Improvement in quality of life (QoL) is a main treatment goal for patients with peripheral arterial illness (PAD). The current study aimed to quantify improvement in the health status of PAD patients post-obit peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial [...] Read more.
Comeback in quality of life (QoL) is a principal treatment goal for patients with peripheral arterial disease (PAD). The electric current report aimed to quantify improvement in the health condition of PAD patients following peripheral revascularization using the peripheral avenue questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation betwixt the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months afterward peripheral revascularization. Mean PAQ summary scores improved significantly 3 months after revascularization (+49.iii ± 15 points, p < 0.001). PAQ scores relating to patient symptoms showed the largest comeback following revascularization. The smallest increases were seen in reported treatment satisfaction (all p'south < 0.001). Equally expected the ABI of treated limbs showed pregnant improvement post-revascularization (p < 0.001). ABI after revascularization correlated with patient-reported changes in the concrete office and QoL domains of the PAQ. 20-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI < 0.fifteen). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI > 0.fifteen following revascularization. In determination, data from the electric current written report suggest a pregnant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization. Full article
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Open up Access Article
Influence of Regular Exercise on Torso Fatty and Eating Patterns of Patients with Intermittent Claudication
Cited by 6 | Viewed by 2690
Abstract
This study examined the touch of regular supervised do on body fat, assessed via anthropometry, and eating patterns of peripheral arterial illness patients with intermittent claudication (IC). Body fat, eating patterns and walking ability were assessed in eleven healthy adults (Control) and historic period- [...] Read more.
This study examined the affect of regular supervised exercise on body fat, assessed via anthropometry, and eating patterns of peripheral arterial affliction patients with intermittent claudication (IC). Trunk fat, eating patterns and walking ability were assessed in 11 healthy adults (Command) and age- and mass-matched IC patients undertaking usual care (n = 10; IC-Con) or supervised exercise (12-months; due north = 10; IC-Ex). At entry, all groups exhibited similar body fat and eating patterns. Maximal walking ability was greatest for Control participants and like for IC-Ex and IC-Con patients. Supervised exercise resulted in significantly greater improvements in maximal walking ability (IC-Ex 148%–170% vs. IC-Con 29%–52%) and smaller increases in body fat (IC-Ex −2.1%–ane.4% vs. IC-Con viii.iv%–10%). IC-Con patients exhibited significantly greater increases in body fat compared with Control at follow-up (8.four%–10% vs. −0.vi%–one.4%). Eating patterns were similar for all groups at follow-upward. The current report demonstrated that regular, supervised practise significantly improved maximal walking power and minimised increase in trunk fat among IC patients without changes in eating patterns. The report supports the utilize of supervised practise to minimize cardiovascular take a chance amid IC patients. Further studies are needed to examine the additional value of other lifestyle interventions such equally diet modification. Total article
Open Admission Article
Immunohistochemical Analysis of Paraoxonases and Chemokines in Arteries of Patients with Peripheral Avenue Illness
Cited by 22 | Viewed by 2772
Abstruse
Oxidative damage to lipids and lipoproteins is implicated in the development of atherosclerotic vascular diseases, including peripheral artery disease (PAD). The paraoxonases (PON) are a group of antioxidant enzymes, termed PON1, PON2, and PON3 that protect lipoproteins and cells from peroxidation and, as [...] Read more.
Oxidative damage to lipids and lipoproteins is implicated in the development of atherosclerotic vascular diseases, including peripheral artery illness (PAD). The paraoxonases (PON) are a group of antioxidant enzymes, termed PON1, PON2, and PON3 that protect lipoproteins and cells from peroxidation and, every bit such, may be involved in protection against the atherosclerosis procedure. PON1 inhibits the production of chemokine (C–C motif) ligand two (CCL2) in endothelial cells incubated with oxidized lipoproteins. PON1 and CCL2 are ubiquitously distributed in tissues, and this suggests a joint localization and combined systemic effect. The aim of the nowadays study has been to analyze the quantitative immunohistochemical localization of PON1, PON3, CCL2 and CCL2 receptors in a series of patients with severe PAD. Portions of femoral and/or popliteal arteries from 66 patients with PAD were obtained during surgical procedures for infra-inguinal limb revascularization. Nosotros used eight normal arteries from donors every bit controls. PON1 and PON3, CCL2 and the chemokine-bounden poly peptide 2, and Duffy antigen/chemokine receptor, were increased in PAD patients. There were no pregnant changes in C–C chemokine receptor blazon ii. Our findings propose that paraoxonases and chemokines play an important role in the development and progression of atherosclerosis in peripheral avenue illness. Full article
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Open Access Article
Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm
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Cited by 27 | Viewed by 2946
Abstruse
Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This report aims to place microRNA (miRNA) expression in aneurysmal inflammatory cells isolated past light amplification by stimulated emission of radiation microdissection from human tissue samples. The distribution of [...] Read more.
Abdominal aortic aneurysm (AAA) is an inflammatory illness associated with marked changes in the cellular limerick of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated past laser microdissection from human being tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. Nosotros observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to two mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened past microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The 3 miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (northward = 2) and M2 macrophages (n = two) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was establish in ATLOs and the ii subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential equally AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA just also as triggers of ATLO evolution. Farther investigations will exist required to evaluate their targets in club to better understand AAA pathophysiology. Full article
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Open Access Commodity
The Potential Role of Dna Methylation in Abdominal Aortic Aneurysms
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Cited by 21 | Viewed past 3102
Abstract
Abdominal aortic aneurysm (AAA) is a complex disorder that has a pregnant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA germination, the precise genetic markers involved and the factors influencing their expression remain an [...] Read more.
Intestinal aortic aneurysm (AAA) is a complex disorder that has a significant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA formation, the precise genetic markers involved and the factors influencing their expression remain an area of ongoing investigation. DNA methylation has been previously used to study gene silencing in other inflammatory disorders and since AAA has an extensive inflammatory component, we sought to examine the genome-wide Dna methylation profiles in mononuclear blood cells of AAA cases and matched not-AAA controls. To this end, we nerveless blood samples and isolated mononuclear cells for DNA and RNA extraction from four all male groups: AAA smokers (n = 11), AAA non-smokers (n = 9), control smokers (due north = 10) and control non-smokers (n = 11). Methylation data were obtained using the Illumina 450k Human being Methylation Dewdrop Chip and analyzed using the R language and multiple Bioconductor packages. Principal component analysis and linear analysis of CpG island subsets identified four regions with significant differences in methylation with respect to AAA: kelch-similar family fellow member 35 (KLHL35), calponin 2 (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and adenylate cyclase ten pseudogene 1 (ADCY10P1). Follow-up studies included RT-PCR and immunostaining for CNN2 and SERPINB9. These findings are novel and suggest DNA methylation may play a role in AAA pathobiology. Total article
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Open Admission Article
Transcriptional (ChIP-Chip) Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human Abdominal Aortic Aneurysm
Cited by xv | Viewed by 3585
Abstract
We investigated transcriptional control of cistron expression in human abdominal aortic aneurysm (AAA). We previously identified 3274 differentially expressed genes in man AAA tissue compared to non-aneurysmal controls. Four expressed transcription factors (ELF1, ETS2, STAT5 and RUNX1) were selected for genome-wide chromatin immunoprecipitation. [...] Read more.
Nosotros investigated transcriptional control of factor expression in man abdominal aortic aneurysm (AAA). We previously identified 3274 differentially expressed genes in human AAA tissue compared to not-aneurysmal controls. Four expressed transcription factors (ELF1, ETS2, STAT5 and RUNX1) were selected for genome-wide chromatin immunoprecipitation. Transcription factor binding was enriched in 4760 distinct genes (FDR < 0.05), of which 713 were differentially expressed in AAA. Functional nomenclature using Gene Ontology (GO), KEGG, and Network Assay revealed enrichment in several biological processes including "leukocyte migration" (FDR = 3.09 × 10− 05) and "intracellular protein kinase pour" (FDR = 6.48 × ten− 05). In the control aorta, the most significant Go categories differed from those in the AAA samples and included "cytoskeleton organization" (FDR = ane.24 × 10− 06) and "small GTPase mediated signal transduction" (FDR = ane.24 × 10− 06). Genes upwards-regulated in AAA tissue showed a highly significant enrichment for Get categories "leukocyte migration" (FDR = one.62 × x− eleven), "activation of immune response" (FDR = eight.44 × x− 11), "T cell activation" (FDR = 4.xiv × 10− 10) and "regulation of lymphocyte activation" (FDR = 2.45 × 10−0 ix), whereas the downward-regulated genes were enriched in Go categories "cytoskeleton organization" (FDR = 7.84 × 10− 05), "muscle cell evolution" (FDR = 1.00 × 10− 04), and "organ morphogenesis" (FDR = 3.00 × ten− 04). Quantitative PCR assays confirmed a sub-gear up of the transcription factor binding sites including those in MTMR11, DUSP10, ITGAM, MARCH1, HDAC8, MMP14, MAGI1, THBD and SPOCK1. Full article
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Open up Admission Article
Inhibitory Effect of Statins on Inflammation-Related Pathways in Homo Intestinal Aortic Aneurysm Tissue
Cited by 41 | Viewed past 3214
Abstract
HMG-CoA (3-hydroxy-three-methylglutaryl-coenzyme A) reductase inhibitors (statins) have been suggested to attenuate abdominal aortic aneurysm (AAA) growth. Yet, the furnishings of statins in human AAA tissues are non fully elucidated. The aim of this study was to investigate the straight furnishings of statins on [...] Read more.
HMG-CoA (3-hydroxy-iii-methylglutaryl-coenzyme A) reductase inhibitors (statins) take been suggested to attenuate abdominal aortic aneurysm (AAA) growth. However, the effects of statins in human AAA tissues are not fully elucidated. The aim of this report was to investigate the direct effects of statins on proinflammatory molecules in human AAA walls in ex vivo culture. Simvastatin strongly inhibited the activation of nuclear gene (NF)-κB induced past tumor necrosis gene (TNF)-α in human being AAA walls, but showed little issue on c-jun Northward-final kinase (JNK) activation. Simvastatin, as well as pitavastatin significantly reduced the secretion of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-2 and epithelial neutrophil-activating peptide (CXCL5) under both basal and TNF-α-stimulated conditions. Similar to statins, the Rac1 inhibitor NSC23766 significantly inhibited the activation of NF-κB, accompanied by a decreased secretion of MMP-9, MCP-2 and CXCL5. Moreover, the upshot of simvastatin and the JNK inhibitor SP600125 was additive in inhibiting the secretion of MMP-nine, MCP-two and CXCL5. These findings indicate that statins preferentially inhibit the Rac1/NF-κB pathway to suppress MMP-9 and chemokine secretion in human being AAA, suggesting a mechanism for the potential effect of statins in attenuating AAA progression. Total commodity
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Open up Access Article
Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms
Cited by 19 | Viewed by 2940
Abstract
Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Prison cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). Nosotros followed upwards the microarray studies by immunohistochemical analyses using antibodies against [...] Read more.
Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human intestinal aortic aneurysm (AAA). We followed up the microarray studies by immunohistochemical analyses using antibodies against nine members of the NK pathway (VAV1, VAV3, PLCG1, PLCG2, HCST, TYROBP, PTK2B, TNFA, and GZMB) and aortic tissue samples from AAA repair operations (due north = 6) and command aortae (northward = 8) from historic period-, sex- and ethnicity-matched donors from autopsies. The results confirmed the microarray results. Two different members of the NK pathway, HCST and GRZB, which act at unlike steps in the NK-pathway, were actively transcribed and translated into proteins in the same cells in the AAA tissue demonstrated by double staining. Furthermore, double staining with antibodies against CD68 or CD8 together with HCST, TYROBP, PTK2B or PLCG2 revealed that CD68 and CD8 positive cells expressed proteins of the NK-pathway but were non the only inflammatory cells involved in the NK-pathway in the AAA tissue. The results provide stiff evidence that the NK Cell Mediated Cytotoxicity Pathway is activated in human AAA and valuable insight for future studies to dissect the pathogenesis of human AAA. Full article
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Review
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Open Access Review
A Review of the Pathophysiology and Potential Biomarkers for Peripheral Artery Disease
Cited past 91 | Viewed past 8858
Abstruse
Peripheral artery disease (PAD) is due to the blockage of the arteries supplying claret to the lower limbs commonly secondary to atherosclerosis. The well-nigh severe clinical manifestation of PAD is critical limb ischemia (CLI), which is associated with a risk of limb loss [...] Read more.
Peripheral artery disease (PAD) is due to the blockage of the arteries supplying claret to the lower limbs usually secondary to atherosclerosis. The most severe clinical manifestation of PAD is critical limb ischemia (CLI), which is associated with a take chances of limb loss and mortality due to cardiovascular events. Currently CLI is mainly treated by surgical or endovascular revascularization, with few other treatments in routine clinical practice. There are a number of issues with current PAD management strategies, such as the difficulty in selecting the appropriate treatments for private patients. Many patients undergo repeated attempts at revascularization surgery, merely ultimately require an amputation. At that place is great involvement in developing new methods to identify patients who are unlikely to benefit from revascularization and to improve management of patients unsuitable for surgery. Circulating biomarkers that predict the progression of PAD and the response to therapies could assist in the management of patients. This review provides an overview of the pathophysiology of PAD and examines the clan between circulating biomarkers and PAD presence, severity and prognosis. While some currently identified circulating markers prove promise, further larger studies focused on the clinical value of the biomarkers over existing take a chance predictors are needed. Full article
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Open Access Review
Clonal Expansion of T Cells in Abdominal Aortic Aneurysm: A Role for Doxycycline as Drug of Choice?
Cited by 12 | Viewed past 2663
Abstract
Most reported studies with fauna models of abdominal aortic aneurysm (AAA) and several studies with patients have suggested that doxycycline favourably modifies AAA; all the same, a recent large long-term clinical trial establish that doxycycline did not limit aneurysm growth. Thus, there is currently no [...] Read more.
Nigh reported studies with animate being models of abdominal aortic aneurysm (AAA) and several studies with patients have suggested that doxycycline favourably modifies AAA; however, a recent large long-term clinical trial found that doxycycline did non limit aneurysm growth. Thus, in that location is currently no convincing testify that doxycycline reduces AAA expansion. Here, we critically review the available experimental and clinical information nigh the furnishings of doxycycline when used as a pharmacological treatment for AAA. The view that AAA can be considered an autoimmune affliction and the observation that AAA tissue shows clonal expansion of T cells is placed in the light of the well-known inhibition of mitochondrial poly peptide synthesis past doxycycline. In T jail cell leukaemia animal models, this inhibitory event of the antibiotic has been shown to impede T cell proliferation, resulting in complete tumour eradication. We suggest that the available prove of doxycycline action on AAA is erroneously ascribed to its inhibition of matrix metalloproteinases (MMPs) past competitive binding of the zinc ion co-factor. Although competitive binding may explain the inhibition of proteolytic activity, information technology does non explain the observed decreases of MMP mRNA levels. We propose that the observed effects of doxycycline are secondary to inhibition of mitochondrial poly peptide synthesis. Provided that serum doxycycline levels are kept at adequate levels, the inhibition will result in a proliferation abort, especially of clonally expanding T cells. This, in turn, leads to the decrease of proinflammatory cytokines that are normally generated by these cells. The drastic change in cell type composition may explain the changes in MMP mRNA and protein levels in the tissue samples. Full commodity
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Open Access Review
Imaging of Small-scale Fauna Peripheral Artery Disease Models: Recent Advancements and Translational Potential
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Cited past 28 | Viewed by 4897
Abstract
Peripheral avenue affliction (PAD) is a broad disorder encompassing multiple forms of arterial illness outside of the centre. As such, PAD development is a multifactorial process with a variety of manifestations. For case, aneurysms are pathological expansions of an artery that tin can lead [...] Read more than.
Peripheral artery affliction (PAD) is a broad disorder encompassing multiple forms of arterial illness outside of the centre. As such, PAD development is a multifactorial procedure with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that tin atomic number 82 to rupture, while ischemic atherosclerosis reduces claret menstruation, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely considering these disorders are commonly undiagnosed or misdiagnosed. Agile areas of research are focused on detecting and characterizing deleterious arterial changes at early on stages using non-invasive imaging strategies, such equally ultrasound, equally well as emerging technologies similar photoacoustic imaging. Before disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular data and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves improve understanding of underlying PAD pathophysiology to develop novel therapeutics and utilise not-invasive imaging techniques in the clinic. Total article
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