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Special Issue "Advances in Peripheral Artery Disease"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology".

Deadline for manuscript submissions: closed (31 January 2015)

Special Issue Editors

Guest Editor
Prof. Jonathan Golledge

1. The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia
2. Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia
Website | E-Mail
Interests: peripheral vascular disease, aortic aneurysm, stroke
Guest Editor
Dr. Joseph V. Moxon

The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia
Website | E-Mail
Interests: peripheral vascular disease, aortic aneurysm, biomarkers, proteomics, systems biology, mouse models, translational research

Special Issue Information

Dear Colleagues,

Peripheral artery disease (PAD) is a broad term encompassing a range of atherosclerotic and aneurysmal conditions within the extra-coronary circulation. PAD is estimated to affect up to 15% of the population aged over 65 years, and significantly increases the risk of major cardiovascular events in affected patients. Incomplete understanding of the mechanisms underpinning PAD results in significant shortfalls in patient management, including a lack of diagnostic markers to screen at-risk populations, difficulty in predicting clinical outcomes for patients with established PAD, and an absence of non-surgical methods to correct disease pathology. To address these limitations, considerable work has been conducted to investigate PAD pathophysiology, often employing mouse models or in vitro approaches. However, the relevance of these findings to the clinical condition, and how results can be translated to improve patient care, is not always immediately clear. This special issue will focus on better understanding the pathophysiology of PAD with specific emphasis on translating research findings to the clinical situation.

Professor Jonathan Golledge
Dr Joseph V Moxon
Guest Editors

Submission

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.

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Keywords

  • peripheral artery disease;
  • atherosclerosis;
  • aneurysm;
  • clinical research;
  • translational research;
  • mouse models;
  • biomarker;
  • drug targets

Published Papers (12 papers)

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Editorial

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Open AccessEditorial The Need for Translational Research to Advance Peripheral Artery Disease Management
Int. J. Mol. Sci. 2015, 16(5), 11125-11130; doi:10.3390/ijms160511125
Received: 6 May 2015 / Revised: 14 May 2015 / Accepted: 15 May 2015 / Published: 18 May 2015
PDF Full-text (616 KB) | HTML Full-text | XML Full-text
Abstract Peripheral artery disease (PAD) is a broad term encompassing a range of atherosclerotic and aneurysmal conditions of the extra-coronary arteries [1]. [...] Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)

Research

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Open AccessArticle Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms
Int. J. Mol. Sci. 2015, 16(5), 11196-11212; doi:10.3390/ijms160511196
Received: 20 November 2014 / Revised: 26 January 2015 / Accepted: 28 January 2015 / Published: 18 May 2015
Cited by 2 | PDF Full-text (6141 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
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 abdominal aortic aneurysm (AAA). We followed up 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 abdominal 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 (n = 6) and control aortae (n = 8) from age-, 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 different 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 not the only inflammatory cells involved in the NK-pathway in the AAA tissue. The results provide strong 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
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Open AccessArticle Inhibitory Effect of Statins on Inflammation-Related Pathways in Human Abdominal Aortic Aneurysm Tissue
Int. J. Mol. Sci. 2015, 16(5), 11213-11228; doi:10.3390/ijms160511213
Received: 26 January 2015 / Revised: 27 March 2015 / Accepted: 30 March 2015 / Published: 18 May 2015
Cited by 5 | PDF Full-text (2247 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins) have 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 study was to investigate the direct effects of statins on
[...] Read more.
HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins) have 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 study 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 factor (NF)-κB induced by tumor necrosis factor (TNF)-α in human AAA walls, but showed little effect on c-jun N-terminal 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 effect of simvastatin and the JNK inhibitor SP600125 was additive in inhibiting the secretion of MMP-9, MCP-2 and CXCL5. These findings indicate that statins preferentially inhibit the Rac1/NF-κB pathway to suppress MMP-9 and chemokine secretion in human AAA, suggesting a mechanism for the potential effect of statins in attenuating AAA progression. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Open AccessArticle Transcriptional (ChIP-Chip) Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human Abdominal Aortic Aneurysm
Int. J. Mol. Sci. 2015, 16(5), 11229-11258; doi:10.3390/ijms160511229
Received: 26 October 2014 / Accepted: 31 December 2014 / Published: 18 May 2015
Cited by 2 | PDF Full-text (8226 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We investigated transcriptional control of gene expression in human abdominal aortic aneurysm (AAA). We previously identified 3274 differentially expressed genes in human 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.
We investigated transcriptional control of gene expression in human abdominal aortic aneurysm (AAA). We previously identified 3274 differentially expressed genes in human AAA tissue compared to non-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 classification using Gene Ontology (GO), KEGG, and Network Analysis revealed enrichment in several biological processes including “leukocyte migration” (FDR = 3.09 × 1005) and “intracellular protein kinase cascade” (FDR = 6.48 × 1005). In the control aorta, the most significant GO categories differed from those in the AAA samples and included “cytoskeleton organization” (FDR = 1.24 × 1006) and “small GTPase mediated signal transduction” (FDR = 1.24 × 1006). Genes up-regulated in AAA tissue showed a highly significant enrichment for GO categories “leukocyte migration” (FDR = 1.62 × 1011), “activation of immune response” (FDR = 8.44 × 1011), “T cell activation” (FDR = 4.14 × 1010) and “regulation of lymphocyte activation” (FDR = 2.45 × 10−09), whereas the down-regulated genes were enriched in GO categories “cytoskeleton organization” (FDR = 7.84 × 1005), “muscle cell development” (FDR = 1.00 × 1004), and “organ morphogenesis” (FDR = 3.00 × 1004). Quantitative PCR assays confirmed a sub-set of the transcription factor binding sites including those in MTMR11, DUSP10, ITGAM, MARCH1, HDAC8, MMP14, MAGI1, THBD and SPOCK1. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Open AccessArticle The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms
Int. J. Mol. Sci. 2015, 16(5), 11259-11275; doi:10.3390/ijms160511259
Received: 7 November 2014 / Accepted: 19 January 2015 / Published: 18 May 2015
Cited by 4 | PDF Full-text (3189 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Abdominal 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
[...] Read more.
Abdominal 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 non-AAA controls. To this end, we collected 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 (n = 10) and control non-smokers (n = 11). Methylation data were obtained using the Illumina 450k Human Methylation Bead 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-like family member 35 (KLHL35), calponin 2 (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and adenylate cyclase 10 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. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Open AccessArticle Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm
Int. J. Mol. Sci. 2015, 16(5), 11276-11293; doi:10.3390/ijms160511276
Received: 30 October 2014 / Revised: 6 January 2015 / Accepted: 12 January 2015 / Published: 18 May 2015
Cited by 6 | PDF Full-text (1283 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of
[...] Read more.
Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three 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 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Figures

Open AccessArticle Immunohistochemical Analysis of Paraoxonases and Chemokines in Arteries of Patients with Peripheral Artery Disease
Int. J. Mol. Sci. 2015, 16(5), 11323-11338; doi:10.3390/ijms160511323
Received: 28 January 2015 / Revised: 15 April 2015 / Accepted: 22 April 2015 / Published: 18 May 2015
Cited by 3 | PDF Full-text (4948 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
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 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 such, may be involved in protection against the atherosclerosis process. PON1 inhibits the production of chemokine (C–C motif) ligand 2 (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 present 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. We used eight normal arteries from donors as controls. PON1 and PON3, CCL2 and the chemokine-binding protein 2, and Duffy antigen/chemokine receptor, were increased in PAD patients. There were no significant changes in C–C chemokine receptor type 2. Our findings suggest that paraoxonases and chemokines play an important role in the development and progression of atherosclerosis in peripheral artery disease. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Open AccessArticle Influence of Regular Exercise on Body Fat and Eating Patterns of Patients with Intermittent Claudication
Int. J. Mol. Sci. 2015, 16(5), 11339-11354; doi:10.3390/ijms160511339
Received: 27 November 2014 / Revised: 7 January 2015 / Accepted: 12 January 2015 / Published: 18 May 2015
Cited by 1 | PDF Full-text (699 KB) | HTML Full-text | XML Full-text
Abstract
This study examined the impact of regular supervised exercise on body fat, assessed via anthropometry, and eating patterns of peripheral arterial disease patients with intermittent claudication (IC). Body fat, eating patterns and walking ability were assessed in 11 healthy adults (Control) and age-
[...] Read more.
This study examined the impact of regular supervised exercise on body fat, assessed via anthropometry, and eating patterns of peripheral arterial disease patients with intermittent claudication (IC). Body fat, eating patterns and walking ability were assessed in 11 healthy adults (Control) and age- and mass-matched IC patients undertaking usual care (n = 10; IC-Con) or supervised exercise (12-months; n = 10; IC-Ex). At entry, all groups exhibited similar body fat and eating patterns. Maximal walking ability was greatest for Control participants and similar 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%–1.4% vs. IC-Con 8.4%–10%). IC-Con patients exhibited significantly greater increases in body fat compared with Control at follow-up (8.4%–10% vs. −0.6%–1.4%). Eating patterns were similar for all groups at follow-up. The current study demonstrated that regular, supervised exercise significantly improved maximal walking ability and minimised increase in body fat amongst IC patients without changes in eating patterns. The study supports the use of supervised exercise to minimize cardiovascular risk amongst IC patients. Further studies are needed to examine the additional value of other lifestyle interventions such as diet modification. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Open AccessArticle Correlation between Patient-Reported Symptoms and Ankle-Brachial Index after Revascularization for Peripheral Arterial Disease
Int. J. Mol. Sci. 2015, 16(5), 11355-11368; doi:10.3390/ijms160511355
Received: 5 November 2014 / Revised: 14 January 2015 / Accepted: 29 January 2015 / Published: 18 May 2015
Cited by 2 | PDF Full-text (993 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial
[...] Read more.
Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation between the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months after peripheral revascularization. Mean PAQ summary scores improved significantly three months after revascularization (+49.3 ± 15 points, p < 0.001). PAQ scores relating to patient symptoms showed the largest improvement following revascularization. The smallest increases were seen in reported treatment satisfaction (all p’s < 0.001). As expected the ABI of treated limbs showed significant improvement post-revascularization (p < 0.001). ABI after revascularization correlated with patient-reported changes in the physical function and QoL domains of the PAQ. Twenty-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI < 0.15). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI > 0.15 following revascularization. In conclusion, data from the current study suggest a significant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)

Review

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Open AccessReview Imaging of Small Animal Peripheral Artery Disease Models: Recent Advancements and Translational Potential
Int. J. Mol. Sci. 2015, 16(5), 11131-11177; doi:10.3390/ijms160511131
Received: 15 February 2015 / Accepted: 10 March 2015 / Published: 18 May 2015
Cited by 4 | PDF Full-text (8182 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead
[...] Read more.
Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier 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 information 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 better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Figures

Open AccessReview Clonal Expansion of T Cells in Abdominal Aortic Aneurysm: A Role for Doxycycline as Drug of Choice?
Int. J. Mol. Sci. 2015, 16(5), 11178-11195; doi:10.3390/ijms160511178
Received: 7 November 2014 / Accepted: 5 February 2015 / Published: 18 May 2015
Cited by 4 | PDF Full-text (721 KB) | HTML Full-text | XML Full-text
Abstract
Most reported studies with animal 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 not limit aneurysm growth. Thus, there is currently no
[...] Read more.
Most reported studies with animal 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 not limit aneurysm growth. Thus, there is currently no convincing evidence that doxycycline reduces AAA expansion. Here, we critically review the available experimental and clinical information about the effects of doxycycline when used as a pharmacological treatment for AAA. The view that AAA can be considered an autoimmune disease and the observation that AAA tissue shows clonal expansion of T cells is placed in the light of the well-known inhibition of mitochondrial protein synthesis by doxycycline. In T cell leukaemia animal models, this inhibitory effect of the antibiotic has been shown to impede T cell proliferation, resulting in complete tumour eradication. We suggest that the available evidence of doxycycline action on AAA is erroneously ascribed to its inhibition of matrix metalloproteinases (MMPs) by competitive binding of the zinc ion co-factor. Although competitive binding may explain the inhibition of proteolytic activity, it does not explain the observed decreases of MMP mRNA levels. We propose that the observed effects of doxycycline are secondary to inhibition of mitochondrial protein synthesis. Provided that serum doxycycline levels are kept at adequate levels, the inhibition will result in a proliferation arrest, 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 article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Figures

Open AccessReview A Review of the Pathophysiology and Potential Biomarkers for Peripheral Artery Disease
Int. J. Mol. Sci. 2015, 16(5), 11294-11322; doi:10.3390/ijms160511294
Received: 16 February 2015 / Revised: 29 March 2015 / Accepted: 8 April 2015 / Published: 18 May 2015
Cited by 6 | PDF Full-text (981 KB) | HTML Full-text | XML Full-text
Abstract
Peripheral artery disease (PAD) is due to the blockage of the arteries supplying blood 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 risk of limb loss
[...] Read more.
Peripheral artery disease (PAD) is due to the blockage of the arteries supplying blood 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 risk 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 problems with current PAD management strategies, such as the difficulty in selecting the appropriate treatments for individual patients. Many patients undergo repeated attempts at revascularization surgery, but ultimately require an amputation. There is great interest 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 association between circulating biomarkers and PAD presence, severity and prognosis. While some currently identified circulating markers show promise, further larger studies focused on the clinical value of the biomarkers over existing risk predictors are needed. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)

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