A randomized controlled trial of standard vs customized graduated elastic compression stockings in patients with chronic venous disease.

OBJECTIVE: This study aimed to compare the efficacy of customized graduated elastic compression stockings (c-GECSs) based on lower leg parameter models with standard GECSs (s-GECSs) in patients with chronic venous disease (CVD). METHODS: In this randomized, single-blind, controlled trial, 79 patients with stage C2 or C3 CVD were assigned to one of two groups: c-GECSs or s-GECSs. The primary outcome was change to Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores at months 1, 3, and 6 as compared with baseline. Secondary outcomes included compliance with wearing ECSs, interface pressure at the smallest circumference of the ankle (point B) and the largest circumference of the calf (point C), and calf volume (CV). RESULTS: There were 13 pairs of s-GECS and 2 pairs of c-GECS that showed pressure values higher than the standard at either point B or C. The c-GECSs were significantly superior to s-GECSs in terms of score improvement at all three time points (month 1, 8.47 [95% confidence interval (CI), 7.47-9.45] vs 5.89 [95% CI, 5.00-6.78]; month 3, 9.60 [95% CI, 8.47-10.72] vs 6.72 [95% CI, 5.62-7.83]; month 6, 7.09 [95% CI, 5.93-8.24] vs 3.92 [95% CI, 2.67-5.18]; P < .0001). Besides, at month 1, the mean daily use time of the c-GECS and s-GECS groups was 10.7 and 9.5 hours, respectively (P < .05). Correlation analysis indicated a negative relationship between local high pressure and daily duration in the s-GECS group (rpb = -0.388; n = 38; P < .05). Variances in pressure were greater in the s-GECSs group. The c-GECSs showed advantage in maintaining pressure. Both c-GECSs and s-GECSs effectively reduced CV (mL), with no significant differences between groups (month 1, 90.0 [95% CI, 71.4-108.5] vs 85.0 [95% CI, 65.6-104.2]; month 3, 93.8 [95% CI, 69.7-117.8] vs 85.9 [95% CI, 65.5-106.2]; month 6, 70.8 [95% CI, 46.5-95.2]) vs 60.8 [95% CI, 44.1-77.5]). CONCLUSIONS: The c-GECSs based on individual leg parameter models significantly improved VEINES-QOL scores and provided stable and enduring pressure as compared with s-GECSs for patients with stage C2 or C3 CVD. Although both c-GECSs and s-GECSs effectively reduced CV, the superior fit and comfort of c-GECSs improved patient compliance. Hence, c-GECSs are a viable alternative for patients who have difficulty tolerating s-GECSs.

Nomogram for predicting pulmonary embolism in gynecologic inpatients with isolated distal deep venous thrombosis.

OBJECTIVE: To investigate the incidence of isolated distal deep venous thrombosis (IDDVT) concurrent with pulmonary embolism (PE) in gynecologic inpatients, analyze the risk factors for IDDVT with PE, and establish a nomogram model for IDDVT patients with PE. METHODS: A total of 260 patients were diagnosed with IDDVT between December 2017 and November 2020. The incidence of PE in these patients was determined using computed tomography pulmonary angiography. Logistic regression analysis was used to identify the related risk factors. On this basis, nomogram risk prediction models were established. RESULTS: Among 260 patients with IDDVT, 106 (40.8%) had concurrent PE, of whom 74 (28.5%) experienced silent PE. Univariate logistic analysis demonstrated statistical significance for body mass index (BMI; P = 0.044), glucocorticoid therapy (P = 0.009), hypertension (P < 0.001), and diabetes (P < 0.001). Multivariate logistic analysis revealed that these were independent risk factors for IDDVT with PE that retained statistical significance. A nomogram based on these factors was constructed to predict PE in patients with IDDVT. Its receiver operating characteristic (ROC) showed an area under the curve of 0.710 (95% confidence interval 0.642-0.779), with prediction sensitivity of 64.2% and prediction specificity of 76.6%. CONCLUSIONS: In the present study, a high prevalence of PE was found in gynecologic inpatients with IDDVT. Glucocorticoid therapy, hypertension, diabetes, and BMI were independent risk factors for IDDVT patients with PE. Taking these risk factors into account, a nomogram risk prediction model was developed to help facilitate early detection of concurrent PE.

Clinical Outcomes of Drug-Coated Balloon Angioplasty in Peripheral Artery Disease Patients With End-Stage Renal Disease.

PURPOSE: The objective was to determine the effectiveness and safety of paclitaxel-coated balloon angioplasty in hemodialysis patients with diabetic nephropathy (DN). MATERIALS AND METHODS: The outcomes of end-stage renal disease (ESRD) patients with peripheral artery disease (PAD) and treated with drug-coated balloon (DCB) angioplasty were retrospectively evaluated. The effectiveness outcomes were clinical improvement of the Rutherford classification and target lesion revascularization (TLR). Safety outcomes were all-cause mortality and amputation. RESULTS: Ninety-seven patients were treated with DCB angioplasty between December 2018 and December 2020. 87 (63.8±10.1 years) achieved technical success. Most patients had a Rutherford classification of at least grade 4. The mean lesion length was 169.8±73.8 mm, almost all had arterial calcification, and 31.0% had annular calcification. Wounds were present in 73.6% of the target limbs. The mean follow-up in this cohort was 13.4±7.4 months. The wound healing rate was 61.5% at the 12-month follow-up. All-cause mortality during 12 months of follow-up was 35.6%, amputation-free survival was 58.6%, and TLR was observed in 13 (15.3%) patients. At 3 and 12 months of follow-up, the Rutherford grade significantly improved (p<0.001). The Cox proportional hazards model revealed that wounds (hazard ratio [HR]=1.404, p=0.023) and annular calcification (HR=2.076, p=0.031) were independent predictors of amputation-free survival. CONCLUSIONS: Drug-coated balloon angioplasty in ESRD patients was effective and safe over the medium term. Wounds and annular calcification were independent predictors of amputation-free survival. CLINICAL IMPACT: The effectiveness of DCB angioplasty in ESRD patients and the factors affecting major outcome prognosis in this population remain limited. This study contributes valuable insights into the effectiveness and safety of paclitaxel-coated balloon angioplasty for PAD in hemodialysis patients. Medical professionals can now regard DCB angioplasty as a viable treatment. Identifying wound presence and annular calcification as predictors of amputation-free survival equips medical practitioners with a more tailored approach to patient management, potentially resulting in enhanced outcomes and more precise treatment strategies.

Identification of immune infiltration-related biomarkers in carotid atherosclerotic plaques.

Atherosclerosis is a chronic lipid-driven inflammatory response of the innate and adaptive immune systems, and it is responsible for several cardiovascular ischemic events. The present study aimed to determine immune infiltration-related biomarkers in carotid atherosclerotic plaques (CAPs). Gene expression profiles of CAPs were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the CAPs and control groups were screened by the "limma" package in R software. Immune cell infiltration between the CAPs and control groups was evaluated by the single sample gene set enrichment analysis. Key infiltrating immune cells in the CAPs group were screened by the Wilcoxon test and least absolute shrinkage and selection operator regression. The weighted gene co-expression network analysis was used to identify immune cell-related genes. Hub genes were identified by the protein-protein interaction (PPI) network. Receiver operating characteristic curve analysis was performed to assess the gene's ability to differentiate between the CAPs and control groups. Finally, we constructed a miRNA-gene-transcription factor network of hub genes by using the ENCODE database. Eleven different types of immune infiltration-related cells were identified between the CAPs and control groups. A total of 1,586 differentially expressed immunity-related genes were obtained through intersection between DEGs and immune-related genes. Twenty hub genes were screened through the PPI network. Eventually, 7 genes (BTK, LYN, PTPN11, CD163, CD4, ITGAL, and ITGB7) were identified as the hub genes of CAPs, and these genes may serve as the estimable drug targets for patients with CAPs.

Development and validation of a graduated compression stockings adherence scale.

OBJECTIVE: Compression therapy with the use of graduated compression stockings (GCSs) is a common treatment strategy for chronic venous disease (CVD). However, there is no uniform and objective standard to assess adherence to the use of GCSs. The aim of this study is to develop and validate a GCS Compliance Scale (GCSAS) to fill gaps in internationally recognized comprehensive scales and provide a useful tool for future research. METHODS: The items included in the GCSAS were based on a review of the literature and open-ended interviews with experts, who screened the initial items using an item-level content validity index. Then, pilot tests were conducted three times with 50 participants. After exclusion of redundant and cross-loading items by exploratory factor analysis, 290 subjects were recruited to evaluate the reliability and validity of the proposed GCSAS. Analyses included internal consistency, test-retest reliability, split-half reliability, construct validity, criterion validity, convergent validity, and discriminant validity. RESULTS: The final GCSAS consisted of 17 items and 5 dimensions. The results of the exploratory factor analysis indicated that the variances of each factor explained were 22.03%, 14.85%, 14.74%, 14.16%, and 13.35%, and all 5 factors explained 79.13% of the variance among the 17 items. The factor loadings of all items were >0.7. Confirmatory factor analysis indicated that the indices were adequate. A significant positive correlation was found between the GCSAS and the Venous Insufficiency Epidemiological and Economic Study - Quality of Life questionnaire scores (r = 0.76, p < 0.001). The Cronbach's alpha coefficient was 0.90, test-retest reliability was 0.81, and split-half reliability was 0.92. CONCLUSIONS: The GCSAS showed good validity and reliability to assess compliance with the use of GCSs among patients with CVD.

Endovascular embolization of visceral artery aneurysm: a retrospective study.

To assess the safety and efficacy of endovascular embolization techniques, we compared the short- to medium-term prognosis of coil embolization for symptomatic visceral aneurysms (SVAA) and asymptomatic visceral aneurysms (ASVAA) to identify risk factors associated with 30-day mortality. Explore the symptom profile and intrinsic associations of SVAA. A retrospective study of 66 consecutive patients at two tertiary care hospitals from 2010 to 2020 compared the short- to mid-term outcomes of 22 symptomatic VAAs and 44 asymptomatic VAAs treated with coil embolization. Univariate and log-rank tests were used to analyze the prognostic impact of SVAA and ASVAA. SVAA group had significantly higher 30-day mortality than ASVAA group (2(9.1%) vs 0, P = 0.042), both patients who died had symptomatic pseudoaneurysms. Perioperative complications such as end-organ ischemia (P = 0.293) and reintervention (P = 1) were similar in both groups. No difference in event-free survival was identified between the two groups (P = 0.900), but we found that the majority of pseudoaneurysms were SVAA (4/5) and that they had a much higher event rate than true aneurysms. In addition, dyslipidemia may be an influential factor in the development of VAA (P = 0.010). Coil embolization is a safe and effective method of treatment for VAA. Most pseudoaneurysms have symptoms such as abdominal pain and bleeding, and in view of their risk, more attention should be paid to symptomatic patients and the nature of the aneurysm should be determined as soon as possible to determine the next stage of treatment.

Three-dimensional laser scanner as a new tool for measuring lower limb volume in patients with chronic venous diseases.

OBJECTIVE: Measurement of lower limb volume in patients with chronic venous disease (CVD) is necessary for assessing severity at the time of diagnosis and evaluating response to therapy administered. Existing methods have some limitations in clinical application and accuracy. The study aimed to investigate the reliability and validity of a three-dimensional laser scanner (3DLS) in measuring the lower limb volume of patients with CVD. METHODS: A total of 30 patients with CVD (mean age, 55.6 ± 8.07 years; mean body mass index, 24.61 ± 1.87) were recruited in a vascular surgery clinic. The lower limb volumes of all participants were measured using the 3DLS and circumferential method (CM). Statistical analysis was conducted to compare the 3DLS and CM. RESULTS: There was a strong correlation between the CM and 3DLS method (r2 = 0.9065). The 3DLS had a high intraoperator and interoperator reliability. A Bland-Altman plot showed satisfactory agreement between the two methods. The 3DLS demonstrated greater bilateral limb differences than CM. CONCLUSIONS: There was satisfactory agreement between the two investigated methods. The 3DLS method was confirmed to be accurate, repeatable, and rapid in measuring the lower limb volume in patients with CVD and is, therefore, suitable for clinical use.

Compression syndromes of the popliteal artery due to intramuscular ganglion cyst of the biceps femoris: A case report and literature review.

Intramuscular ganglion cyst (IMGC) is a very rare lesion with an unidentified pathogeny that originates within the muscle. We encountered a case of 49-year-old man who complained of intermittent claudication in the right lower limb for 2 months. An intramuscular ganglion cyst in the biceps femoris muscle was diagnosed and located by Computed tomography angiography (CTA) and magnetic resonance imaging (MRI), which compressed the popliteal artery and resulted in ischemia in the right lower limb. Six months after surgical resection, there was no recurrence of the cyst and the popliteal artery was patency. We describe this case with a review of the relevant literature.

Combination of Percutaneous Rotational Thrombectomy and Drug-Coated Balloon for Treatment of Femoropopliteal Artery Nonembolic Occlusion: 12-Month Follow-up.

PURPOSE: To evaluate safety and efficacy of percutaneous mechanical thrombectomy using the Rotarex catheter combined with drug-coated balloon (DCB) in treatment of femoropopliteal artery occlusive disease. MATERIALS AND METHODS: Between January 2016 and February 2018, 81 patients with acute or subacute femoropopliteal artery occlusions were treated with the Rotarex catheter combined with DCB. Lesions were classified according to the onset of symptoms as acutely (< 14 d) or subacutely (14 d to 3 mo) occluded. The mean lesion length was 12.1 cm ± 6.7. The primary endpoint was target lesion patency at 1 year as evaluated by duplex ultrasound (peak systolic velocity ratio < 2.4) and freedom from clinically indicated target lesion revascularization. Amputation rate, major adverse events, and ankle-brachial index at 12 months were evaluated. RESULTS: Technical success rate was 100% (n = 81). Bailout stents were necessary in 14 patients owing to residual stenosis or flow-limiting dissection. Additional thrombolysis was applied in 10 interventions. No major adverse events occurred during hospital stay. There were 9 restenosis cases during the 12-month follow-up period. Primary patency rate was 87.3% (62/71), and freedom from target lesion revascularization rate was 90.1% (64/71). Ankle-brachial index significantly increased from 0.46 ± 0.15 to 0.77 ± 0.14 during follow-up. The amputation rate was 1.4% at 12 months. CONCLUSIONS: These initial data from 2 centers suggest that the combination of the Rotarex catheter and DCB may be safe and effective for treatment of acute or subacute thrombotic femoropopliteal occlusion with superior immediate and midterm results achieved.

Once-daily vs. twice-daily dosing of enoxaparin for the management of venous thromboembolism: A systematic review and meta-analysis.

The present study aimed to determine whether there is any difference in the efficacy and safety of once-daily vs. twice-daily enoxaparin when used for the initial treatment of venous thromboembolism (VTE). The PubMed, Embase, Cochrane Central Register of Controlled Trials, Science Direct and Google Scholar databases were searched for studies comparing once-daily and twice-daily enoxaparin for the initial treatment of VTE added from inception up to 1st October 2019. Studies utilizing any other low-molecular-weight heparin and using enoxaparin for VTE prophylaxis were excluded. A total of 6 studies were included in the systematic review and 5 in the meta-analysis. Only one study was a randomized controlled trial (RCT). Pooled analysis of 460 patients receiving once-daily enoxaparin and 464 patients receiving twice-daily enoxaparin indicated no significant difference between the two dosing regimens regarding VTE recurrence [odds ratio (OR)=1.48, 95%CI: 0.75-2.89, P=0.26; I2=0%]. No significant difference in major hemorrhagic complications was noted (OR=1.21, 95%CI: 0.52-2.81, P=0.66; I2=0%). Sub-group analysis based on study type and use of enoxaparin for bridging therapy did not change the overall results. In cancer patients, no statistically significant difference in the recurrence of VTE was obtained between once-daily and twice-daily enoxaparin, but the confidence intervals were wide with a tendency to favor twice-daily dosing (OR=2.28, 95%CI: 0.91-5.75, P=0.08; I2=0%). The overall quality of the studies was determined to be average. To conclude, while the present results suggested no significant difference in efficacy and safety of once-daily vs. twice-daily enoxaparin when used for the initial treatment of VTE, the quality of the evidence may not have been sufficiently high to support the conclusions with confidence. Further high-quality and adequately powered RCTs are required to corroborate the present results.

A microRNA delivery carrier for hepatic carcinoma therapy using layer-by-layer self-assembled mesenchymal stem cells.

BACKGROUND: Several microRNAs (miRNAs), such as miR101, have been reported to be effective for hepatocellular carcinoma (HCC) therapy in preclinical studies; while its further application is hampered due to the lack of desirable delivery systems. Based on the characteristics of mesenchymal stem cells (MSCs), including good biocompatibility and tropism to HCC, the current study was designed to investigate whether miR101-loaded MSCs (miR101-MSCs) using layer-by layer (LbL) self-assembled gelatin and alginate could target the delivery of miR101 to HCC. METHODS: The characterization of miR101-loaded MSCs was determined by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Zeta potential analysis. The tropism and of miR101-MSCs to HCC were detected by Transwell chamber assay, and the anti-tumor potential of miR101-MSCs against HCC was examined by Annexin V-FITC/PI staining, BrdU incorporation assay, and immunoblotting with antibodies against proliferating cell nuclear antigen (PCNA) and caspase-3. RESULTS: The results showed that a thin LbL film containing miR101 was encapsulated on the surface of MSCs. Furthermore, miR101-loaded MSCs had a tropism to hepatoma cells. Finally, treatment of BEL-7402 cells, an HCC cell line, with miR101-loaded MSCs led to significant proliferation inhibition and apoptosis of BEL-7402 cells. CONCLUSIONS: These in vitro findings suggest that MSCs loaded with miRNA by LbL self-assembly may be a promising and minimally invasive approach for targeted treatment of HCC.

Ablation and Inhibition of the Immunoproteasome Catalytic Subunit LMP7 Attenuate Experimental Abdominal Aortic Aneurysm Formation in Mice.

Low-molecular mass protein 7 (LMP7) is a proteolytic subunit of the immunoproteasome that is involved in regulating inflammatory responses. However, the role of LMP7 in the pathogenesis of abdominal aortic aneurysm (AAA) remains unknown. In this study, ApoE knockout (KO) or LMP7/ApoE double KO (dKO) mice were infused with angiotensin II (Ang II, 1000 ng/kg per minute) for up to 28 d. We found that LMP7 expression was significantly upregulated in AAA tissues from ApoE KO mice and human patients. Moreover, Ang II infusion markedly increased the incidence and severity of AAA in ApoE KO mice, which was considerably reduced in LMP7/ApoE dKO mice. Histological alterations, including aortic wall thickening, collagen deposition, elastin fragmentation, and vascular smooth muscle cell apoptosis in AAA tissue of ApoE KO mice, were also significantly attenuated in LMP7/ApoE dKO mice. Interestingly, LMP7/ApoE dKO mice showed a marked reduction of infiltration of CD3+ T cells, especially CD4+ T cells in AAA tissues compared with ApoE KO mice. Moreover, ablation of LMP7 substantially inhibited the differentiation of CD4+ T cells into Th1 and Th17 cells by reducing the activation of multiple transcriptional factors. We also investigated the effects of an LMP7-specific inhibitor PR-957 (also known as ONX 0914) on AAA formation in ApoE KO mice. PR-957 treatment could reduce the AAA incidence and severity. In conclusion, our results provide, to our knowledge, novel evidence that ablation or pharmacological inhibition of LMP7 attenuates Ang II-induced AAA formation, and LMP7 might be a novel therapeutic target for treating AAA in humans.

Chemokine (C-X-C motif) receptor 2 blockade by SB265610 inhibited angiotensin II-induced abdominal aortic aneurysm in Apo E-/- mice.

Inflammation plays a critical role in the development of abdominal aortic aneurysm (AAA). Chemokine receptor CXCR2 mediates inflammatory cell chemotaxis in several diseases. However, the role of CXCR2 in AAA and the underlying mechanisms remain unknown. In this study, we found that the CXCR2 expressions in AAA tissues from human and angiotensin II (Ang II)-infused apolipoprotein E knockout (Apo E-/-) mice were significantly increased. The pharmacological inhibition of CXCR2 (SB265610) markedly reduced Ang II-induced AAA formation. Furthermore, SB265610 treatment significantly reduced collagen deposition, elastin degradation, the metal matrix metalloprotease expression and accumulation of macrophage cells. In conclusion, these results showed CXCR2 plays a pathogenic role in AAA formation. Inhibition of CXCR2 pathway may represent a novel therapeutic approach to treat AAA.

Renal Function Preservation in Surgical Resection of Primary Inferior Vena Cava Leiomyosarcoma Involving the Renal Veins.

OBJECTIVE: This retrospective study aimed to show the practice of preserving renal function during curative resection of inferior vena cava leiomyosarcoma (IVCL) involving the renal veins at a single institution over a 7 year period. MATERIALS AND METHODS: From February 2009 to February 2017, 10 patients (6 women; median age 49 years) with IVCL involving the renal veins were treated surgically at Peking Union Medical College Hospital. En bloc resections were performed in all patients, and the renal outflows were preserved in eight patients using a new method: venoplasty of the renal ostia (VRO). Data regarding patient details, pre-operative preparation, surgical procedures, post-operative recovery, and follow-up results were obtained and reviewed retrospectively. RESULTS: Computed tomography and intra-operative examinations revealed that renal vein confluences were involved but not invaded in all cases except Patient 4. All patients underwent curative en bloc tumour excision; a right nephrectomy was performed in only one patient (Patient 4) whose tumour invaded the right renal vein. The mean operation time was 358 min and the mean blood loss 1935 mL. At a median follow-up of 54.5 months, the 5 year local recurrence, distant metastasis, overall survival, and disease-free survival rates were 20%, 10%, 68.6%, and 38.1%, respectively. CONCLUSIONS: Venoplasty of the renal ostia is an effective method of preserving the renal veins and reconstructing renal outflow.

Change of Serum Angiopoietin-like Protein 2 and Its Significance in Patients with Arteriosclerotic Occlusion.

Objective To investigated the changes of angiopoietin-like protein 2(Angptl2) in patients with arteriosclerotic occlusion (ASO). Methods A total of 140 subjects including 75 ASO patients (ASO group) and 65 healthy subjects (control group) were enrolled in this study. Angptl2 and adiponectin were evaluated by using enzyme-linked immunosorbent assay. Biochemical data and high sensitive C reactive protein were measured and recorded as well. Results Compared to the control group,the ASO group presented with significantly higher level of plasma Angptl2 [(13.55±9.17) µg/L vs. (9.04±4.79) µg/L,P=0.010]. Plasma Angptl2 level of critical limb ischemia subjects was significantly higher than that of intermittent claudication subjects [(17.01±10.20)µg/L vs. (10.53±6.97) µg/L,P=0.003]. The best diagnostic cutoff value of Angptl2 was 13.67 µg/L,with a sensitivity of 60.34% and a specificity of 81.25%. In addition,type 2 diabetes mellitus patients with ASO exhibited significantly higher serum Angptl2 levels [(18.67±9.84)µg/L] than those without ASO [(13.01±3.47) µg/L] (P=0.021). In ASO group,serum Angptl2 levels were negatively correlated with ankle brachial index (r=-0.244,P=0.035). Conclusion The plasma level of Angptl2 increases in ASO patients. Its level is remarkably increased when the disease progressions to critical limb ischemia. Angptl2 can be a potential biological marker of disease progression.

Angiopoietin-related growth factor is independently associated with lower extremity peripheral arterial disease.

AIMS: The present study investigated the association of serum levels of angiopoietin-related growth factor (AGF) with lower extremity peripheral arterial disease (LEPAD). METHODS: The study group is comprised of 105 patients with lower extremity peripheral arterial disease. The control group consisted of 80 individuals without lower extremity peripheral arterial disease. Serum AGF concentrations were determined by enzyme-linked immunosorbent assay. The relationship between AGF and clinical and biochemical parameters was studied. Besides, this study analyzed AGF levels in LEPAD patients according to disease severity and evaluated the prognostic value of AGF for amputation and mortality in LEPAD patients after a follow-up period of 1.7years. RESULTS: Median serum AGF levels were significantly higher in LEPAD group (103.70±64.69ng/mL) as compared with control group (53.83±37.87ng/mL) (P<0.001). In addition, T2DM patients with LEPAD exhibited markedly higher serum AGF concentrations (118.7±60.90ng/mL) than those without LEPAD (60.23±32.62ng/mL) (P<0.0001). Moreover, LEPAD positively predicted AGF concentrations in multivariate linear regression analysis (P<0.0001). Serum AGF levels were independently associated with LEPAD in binary logistic regression analysis model. Among LEPAD patients, those with critical limb ischemia (n=43) showed higher AGF levels (124.9±73.9 vs. 88.98±53.26ng/mL, P=0.01) compared with those with intermittent claudication (n=62). Furthermore, patients with the highest AGF tertile had an increased all-cause mortality and cardiovascular mortality (P=0.033 and P=0.025, respectively). CONCLUSIONS: Our results suggested that lower extremity peripheral artery disease was positively associated with AGF serum levels. High serum AGF level was a potential risk factor for LEPAD and associates with disease severity and poor outcome in LEPAD patients.

Genetic and Pharmacologic Inhibition of the Chemokine Receptor CXCR2 Prevents Experimental Hypertension and Vascular Dysfunction.

BACKGROUND: The recruitment of leukocytes to the vascular wall is a key step in hypertension development. Chemokine receptor CXCR2 mediates inflammatory cell chemotaxis in several diseases. However, the role of CXCR2 in hypertension development and the underlying mechanisms remain unknown. METHODS: Angiotensin II (490 ng·kg-1·min-1) or deoxycorticosterone acetate (DOCA) salt-induced mouse hypertensive models in genetic ablation, pharmacologic inhibition of CXCR2, and adoptive bone marrow transfer mice were used to determine the role of CXCR2 in hypertension (measured by radiotelemetry and tail-cuff system), inflammation (verified by flow cytometry and quantitative real-time polymerase chain reaction [PCR] analysis), vascular remodeling (studied by haematoxylin and eosin and Masson's trichrome staining), vascular dysfunction (assessed by aortic ring), and oxidative stress (indicated by nicotinamide adenine dinucleotide phosphate [NADPH] oxidase activity, dihydroethidium staining, and quantitative real-time PCR analysis). Moreover, the blood CXCR2+ cells in normotensive controls and hypertension patients were analyzed by flow cytometry. RESULTS: Angiotensin II significantly upregulated the expression of CXCR2 mRNA and protein and increased the number of CD45+ CXCR2+ cells in mouse aorta (n=8 per group). Selective CXCR2 knockout (CXCR2-/-) or pharmacological inhibition of CXCR2 markedly reduced angiotensin II- or DOCA-salt-induced blood pressure elevation, aortic thickness and collagen deposition, accumulation of proinflammatory cells into the vascular wall, and expression of cytokines (n=8 per group). CXCR2 inhibition also ameliorated angiotensin II-induced vascular dysfunction and reduced vascular superoxide formation, NADPH activity, and expression of NADPH oxidase subunits (n=6 per group). Bone marrow reconstitution of wild-type mice with CXCR2-/- bone marrow cells also significantly abolished angiotensin II-induced responses (n=6 per group). It is important to note that CXCR2 blockade reversed established hypertension induced by angiotensin II or DOCA-salt challenge (n=10 per group). Furthermore, we demonstrated that CXCR2+ proinflammatory cells were higher in hypertensive patients (n=30) compared with normotensive individuals (n=20). CONCLUSIONS: Infiltration of CXCR2+ cells plays a pathogenic role in arterial hypertension and vascular dysfunction. Inhibition of CXCR2 pathway may represent a novel therapeutic approach to treat hypertension.