Localization of a gene for peripheral arterial occlusive disease to chromosome 1p31.
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ABSTRACT:
SUBMITTER: Gudmundsson G
PROVIDER: S-EPMC384938 | biostudies-other | 2002 Mar
REPOSITORIES: biostudies-other
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Project description:Background: Observational studies support an association between periodontitis (PD) and atherosclerotic vascular disease, but little is known specifically about peripheral arterial occlusive disease (PAOD). To systematically review the evidence for an association between PD and PAOD. Medline via PubMed. We searched the Pubmed database for original studies, case reports, case series, meta-analyses and systematic reviews that assessed whether there is an association between PD (all degrees of severity) and PAOD (all degrees of severity). The reporting of this systematic review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement following the Population, Intervention, Control, and Outcome (PICO) format. 17 out of 755 detected studies were included in the qualitative synthesis. Nine studies demonstrated associations between PD and PAOD, and two studies reported associations between tooth loss and PAOD. Six studies addressed the pathomechanism regarding PD as a possible trigger for PAOD. No study that dismissed an association could be detected. Odds ratios or hazard ratios ranged from 1.3 to 3.9 in four large cohort studies after adjusting for established cardiovascular risk factors. The presented evidence supports a link between PD and PAOD. Further studies which address the temporality of PD and PAOD and randomized controlled intervention trials examining the causal impact of PD on PAOD are needed. Although our results cannot confirm a causal role of PD in the development of PAOD, it is likely that PD is associated with PAOD and plays a contributing role.
| S-EPMC6627595 | biostudies-literature
Project description:BackgroundPeripheral arterial disease (PAD), a major manifestation of atherosclerosis, is associated with significant cardiovascular morbidity, limb loss and death. However, mechanisms underlying the genesis and progression of the disease are far from clear. Genome-wide gene expression profiling of clinical samples may represent an effective approach to gain relevant information.ResultsAfter histological classification, a total of 30 femoral artery samples, including 11 intermediate lesions, 14 advanced lesions and 5 normal femoral arteries, were profiled using Affymetrix microarray platform. Following real-time RT-PCR validation, different algorithms of gene selection and clustering were applied to identify differentially expressed genes. Under a stringent cutoff, i.e., a false discovery rate (FDR) <0.5%, we found 366 genes were differentially regulated in intermediate lesions and 447 in advanced lesions. Of these, 116 genes were overlapped between intermediate and advanced lesions, including 68 up-regulated genes and 48 down-regulated ones. In these differentially regulated genes, immune/inflammatory genes were significantly up-regulated in different stages of PAD, (85/230 in intermediate lesions, 37/172 in advanced lesions). Through literature mining and pathway analysis using different databases such as Gene Ontology (GO), and the Kyoto Encyclopedia of Gene and Genomics (KEGG), genes involved in immune/inflammatory responses were significantly enriched in up-regulated genes at different stages of PAD(p < 0.05), revealing a significant correlation between immune/inflammatory responses and disease progression. Moreover, immune-related pathways such as Toll-like receptor signaling and natural killer cell mediated cytotoxicity were particularly enriched in intermediate and advanced lesions (P < 0.05), highlighting their pathogenic significance during disease progression.ConclusionLines of evidence revealed in this study not only support previous hypotheses, primarily based on studies of animal models and other types of arterial disease, that inflammatory responses may influence the development of PAD, but also permit the recognition of a wide spectrum of immune/inflammatory genes that can serve as signatures for disease progression in PAD. Further studies of these signature molecules may eventually allow us to develop more sophisticated protocols for pharmaceutical interventions.
| S-EPMC2529314 | biostudies-literature
Project description:BackgroundPeripheral arterial occlusive disease (PAOD) is a global public health concern that decreases the quality of life of the patients and can lead to disabilities and death. The aim of this study was to identify the genes and pathways associated with PAOD pathogenesis, and the potential therapeutic targets.MethodsDifferentially expressed genes (DEGs) and miRNAs related to PAOD were extracted from the GSE57691 dataset and through text mining. Additionally, bioinformatics analysis was applied to explore gene ontology, pathways and protein-protein interaction of those DEGs. The potential miRNAs targeting the DEGs and the transcription factors (TFs) regulating miRNAs were predicted by multiple different databases.ResultsA total of 59 DEGs were identified, which were significantly enriched in the inflammatory response, immune response, chemokine-mediated signaling pathway and JAK-STAT signaling pathway. Thirteen genes including IL6, CXCL12, IL1B, and STAT3 were hub genes in protein-protein interaction network. In addition, 513 miRNA-target gene pairs were identified, of which CXCL12 and PTPN11 were the potential targets of miRNA-143, and IL1B of miRNA-21. STAT3 was differentially expressed and regulated 27 potential target miRNAs including miRNA-143 and miRNA-21 in TF-miRNA regulatory network.ConclusionIn summary, inflammation, immune response and STAT3-mediated miRNA-target genes axis play an important role in PAOD development and progression.
| S-EPMC7250035 | biostudies-literature
Project description:An influenza vaccination might reduce the risk of incident peripheral arterial occlusive disease (PAOD) in patients with chronic kidney disease (CKD), but supporting evidence is limited. This case-crossover study analyzed data from Taiwan's real-world National Health Insurance Research Database. This study included elderly (≥ 67 years old) patients with CKD having incident PAOD from January 1, 2006, to June 30, 2015. We defined 1 year before PAOD onset as the index date for the self-control group. A conditional logistic regression model was used to investigate exposure to an influenza vaccination for estimating the risk for incident PAOD following vaccination. In total, this study included 46,782 elderly patients with CKD having incident PAOD. The odds ratios for incident PAOD were 0.85 (95% confidence interval 0.77-0.94), 0.85 (0.79-0.92), 0.84 (0.79-0.90), and 0.85 (0.81-0.90) at 1, 2, 3, and 4 months after an influenza vaccination, respectively. We observed consistent results for the subgroups of patients with CKD and concomitant diabetes. However, we did not observe any beneficial effects of influenza vaccination in patients with advanced CKD or end-stage renal disease. This study demonstrated that influenza vaccination may be associated with a reduced risk of incident PAOD among patients with early-stage CKD.
| S-EPMC7921588 | biostudies-literature
Project description: Not available
| S-EPMC6517203 | biostudies-literature
Project description:BACKGROUND:Plastic and reconstructive surgeons are commonly faced with chronic ulcerations and consecutive wound infections of the feet as complications in patients with diabetes and/or peripheral arterial occlusive disease (PAOD). Microcirculatory changes seem to play an important role. However, the evaluation of functional changes in the soft tissue microcirculation at the plantar foot using combined Laser-Doppler and Photospectrometry System has not yet been performed in patients with DM or PAOD. METHODS:A prospective, controlled cohort study was designed consisting of a total of 107 subjects allocated to 1 of 3 groups-group A: healthy subjects (57% males, 63.3 y); group B: patients with diabetes mellitus (DM) (53% males, 59.4 y); and group C: patients with PAOD (81% males, 66.1 y). Microcirculatory data were assessed using a combined Laser-Doppler and Photospectrometry System. RESULTS:Global cutaneous oxygen saturation microcirculation at the plantar foot of healthy individuals was 8.4% higher than in patients with DM and 8.1% higher than in patients with PAOD (both P = 0.033). Patients with diabetes did not show significant differences in global cutaneous blood flow when compared with either healthy subjects or patients suffering from PAOD. CONCLUSIONS:Functional microcirculation at the plantar foot differs between healthy subjects and patients suffering from diabetes or PAOD of the same age. Patients with either diabetes or PAOD demonstrate deteriorated cutaneous oxygen saturation with equivalent blood perfusion at the plantar foot. More clinical studies have to be conducted to evaluate therapeutical methods that might ameliorate cutaneous oxygen saturation within diabetic foot disease and PAOD.
| S-EPMC4174050 | biostudies-literature
Project description:AIM:Peripheral artery disease (PAD) is a vascular disease affecting peripheral circulation. Recently, genome-wide association studies revealed a relationship between single nucleotide polymorphisms (SNPs) in ADAMTS7 (a disintegrin and metalloprotease with thrombospondin motif 7) and atherosclerosis. In this study, we aimed to determine ADAMTS7 expression in peripheral blood mononuclear cells (PBMCs) and the frequency of ADAMTS7 rs1994016 and rs3825807 polymorphisms in a sample of Turkish patients with PAD, and to evaluate the association of matrix metalloproteinase (MMP) levels with PAD development. METHODS:In this case-control study, ADAMTS7mRNA and protein expression was determined using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively, and rs1994016 and rs3825807 variants in ADAMTS7 were determined by real-time PCR in 115 PAD patients and 116 healthy controls. Plasma levels of nine MMPs were determined using a multiplex immunoassay system. RESULTS:ADAMTS7mRNA levels were significantly higher in PAD patients than in controls (t=-2.75, P=.007). There was no significant difference in the frequencies of rs1994016 and rs3825807 between PAD patients and controls (P>.05). In PAD patients, ADAMTS7mRNA levels were significantly increased for the CC genotype of rs1994016 (t=-2.31, P=.026) and TT genotype of rs3825807 (t=-2.23, P=.032). Furthermore, plasma levels of MMP-1, MMP-3, MMP-7, MMP-10, MMP-12, and MMP-13 were significantly higher in PAD patients than in controls (P<.05). CONCLUSION:This is the first report of the relationship between PAD and ADAMTS7 expression and the effects of the rs1994016 and rs3825807 variants on PAD development. ADAMTS7 may be associated with PAD development.
| S-EPMC6817273 | biostudies-literature
Project description:BackgroundThis study aimed to determine the prevalence of genetic and environmental vascular risk factors in non diabetic patients with premature peripheral arterial disease, either peripheral arterial occlusive disease or thromboangiitis obliterans, the two main entities of peripheral arterial disease, and to established whether some of them are specifically associated with one or another of the premature peripheral arterial disease subgroups.Methods and resultsThis study included 113 non diabetic patients with premature peripheral arterial disease (diagnosis <45-year old) presenting either a peripheral arterial occlusive disease (N?=?64) or a thromboangiitis obliterans (N?=?49), and 241 controls matched for age and gender. Both patient groups demonstrated common traits including cigarette smoking, low physical activity, decreased levels of HDL-cholesterol, apolipoprotein A-I, pyridoxal 5'-phosphate (active form of B6 vitamin) and zinc. Premature peripheral arterial occlusive disease was characterized by the presence of a family history of peripheral arterial and carotid artery diseases (OR 2.3 and 5.8 respectively, 95% CI), high lipoprotein (a) levels above 300 mg/L (OR 2.3, 95% CI), the presence of the factor V Leiden (OR 5.1, 95% CI) and the glycoprotein Ia(807T,837T,873A) allele (OR 2.3, 95% CI). In thromboangiitis obliterans group, more patients were regular consumers of cannabis (OR 3.5, 95% CI) and higher levels in plasma copper has been shown (OR 6.5, 95% CI).ConclusionsAccording to our results from a non exhaustive list of study parameters, we might hypothesize for 1) a genetic basis for premature peripheral arterial occlusive disease development and 2) the prevalence of environmental factors in the development of thromboangiitis obliterans (tobacco and cannabis). Moreover, for the first time, we demonstrated that the 807T/837T/873A allele of platelet glycoprotein Ia may confer an additional risk for development of peripheral atherosclerosis in premature peripheral arterial occlusive disease.
| S-EPMC3606168 | biostudies-literature
Project description:ObjectivesPeripheral arterial occlusive disease (PAOD) and periodontitis are common chronic diseases, which together affect almost 1 billion people worldwide. There is growing evidence suggesting a relationship between chronic inflammatory conditions such as periodontitis and PAOD. This study aims to determine an association between both entities using high quality research data and multiple phenotypes derived from an epidemiological cohort study.DesignThis population-based cross-sectional cohort study included data from 3271 participants aged between 45 and 74 years enrolled in the Hamburg City Health Study (NCT03934957).Material & methodsAn ankle-brachial-index below 0.9, color-coded ultrasound of the lower extremity arteries, and survey data was used to identify participants with either asymptomatic or symptomatic PAOD. Periodontitis data was collected at six sites per tooth and included the probing depth, gingival recession, clinical attachment loss, and bleeding on probing index. Multivariate analyses using logistic regression models were adjusted for variables including age, sex, smoking, education, diabetes, and hypertension.ResultsThe baseline characteristics differed widely between participants neither affected by periodontitis nor PAOD vs. the group where both PAOD and severe periodontitis were identified. A higher rate of males, higher age, lower education level, smoking, diabetes, and cardiovascular disease was observed in the group affected by both diseases. After adjusting, presence of severe periodontitis (odds ratio 1.265; 97.5% CI 1.006-1.591; p = 0.045) was independently associated with PAOD.ConclusionIn this cross-sectional analysis of a prospective cohort study, an independent association between periodontitis and PAOD was revealed. The results of the current study emphasize a potential for preventive medicine in an extremely sensitive target population. Future studies should determine the underlying factors modifying the relationship between both diseases.
| S-EPMC8152001 | biostudies-literature
Project description:Background An increasing number of patients with a peripheral arterial occlusive disease were put on statins during the past years. This study assessed whether statin therapy was effective and safe for these new users. Methods and Results Using health insurance claims data from Germany's second-largest insurance fund, BARMER, we identified patients with peripheral arterial occlusive disease who had index revascularization between 2008 and 2018 without prior statin therapy. We compared patients with and without statin therapy in addition to antithrombotics during the first quarter after discharge (new users versus nonusers). Outcomes were all-cause mortality, cardiovascular events, and incident major amputation for effectiveness and incident diabetes mellitus and incident myopathy for safety. Propensity score matching was used to balance the study groups. All analyses were stratified into patients with chronic limb-threatening ischemia and intermittent claudication. A total of 22 208 patients (mean age 71.1 years and 50.3% women) were included in the study. In 10 922 matched patients, statin initiation was associated with lower all-cause mortality (chronic limb-threatening ischemia: hazard ratio [HR], 0.75 [95% CI, 0.68-0.84]; intermittent claudication: HR, 0.80 [95% CI, 0.70-0.92]), lower risk of major amputation in patients with chronic limb-threatening ischemia (HR, 0.73; 95% CI, 0.58-0.93) and lower risk of cardiovascular events (hazard ratio, 0.80; 95% CI, 0.70-0.92) in patients with intermittent claudication during 5 years of follow-up. Safety outcomes did not differ among the study groups. Conclusions Initiating statin therapy in patients with peripheral arterial occlusive disease after index revascularization is efficient and safe with an effect size comparable to earlier studies. Awareness campaigns for evidence-based optimal pharmacological treatment among patients are recommended.
| S-EPMC7763713 | biostudies-literature