interleukin-8 and Peripheral-Arterial-Disease

Topics: Atherosclerosis; Biomarkers; Humans; Interleukin-6; Interleukin-8; Peripheral Arterial Disease; Prognosis; Risk Factors

Patients with Severe Limb Ischemia (SLI) have a high risk of amputation and mortality. Here, we investigated a panel of serum biomarkers with the aim of identifying biomarkers for major events and mechanisms that contribute to disease progression in established SLI. A panel of biomarkers including GROα, HGF, SCF, SCGFβ, SDF1α, TRAIL, IL-6, IL-8, FGFβ, GCSF, GMCSF, IP10, MCP1, PDGFbb, RANTES, TNFα, VEGF, sICAM, sVCAM, TM, and E-selectin was measured in serum samples from a subset (n = 108) of the JUVENTAS cohort. The primary outcome was major events, defined as major amputation or death. The inflammatory biomarkers IL-6, IL-8, GROα and IP-10 were significantly elevated in patients who reached a major endpoint. Results were validated in a secondary cohort (n = 146). Cox regression showed that adjusted hazard ratios were 1.40 (95% CI: 1.15-1.70, p = 0.0007) and 1.48 (95% CI 1.16-1.87, p = 0.001) for IL-6 and IP-10 in a fully adjusted model containing both biomarkers. A prediction model using IL-6 and IP-10 showed predictive accuracy with an AUC of ~ 78% in both discovery and validation cohorts, which is higher than previously published models. We conclude that inflammatory biomarkers predict major events in patients with SLI and allow the creation of biomarker-based risk-prediction models.

Topics: Aged; Amputation, Surgical; Biomarkers; Chemokine CXCL1; Chemokine CXCL10; Chemokines; Cytokines; Extremities; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Ischemia; Male; Middle Aged; Peripheral Arterial Disease; Predictive Value of Tests; Proportional Hazards Models; Survival Analysis

We compared apoptosis, cellular oxidative stress, and inflammation of cultured endothelial cells treated with sera from 130 patients with peripheral artery disease (PAD) and a control group of 36 patients with high burden of comorbid conditions and cardiovascular risk factors. Second, we compared circulating inflammatory, antioxidant capacity, and vascular biomarkers between the groups. The groups were not significantly different (P > .05) on apoptosis, hydrogen peroxide, hydroxyl radical antioxidant capacity, and nuclear factor κ-light-chain enhancer of activated B cells. Circulating tumor necrosis factor α (TNF-α; P = .016) and interleukin 8 (IL-8; P = .006) were higher in the PAD group, whereas vascular endothelial growth factor A (VEGF-A; P = .023) was lower. The PAD does not impair the endothelium beyond that which already occurs from comorbid conditions and cardiovascular risk factors in patients with claudication. However, patients with PAD have lower circulating VEGF-A than the control group and higher circulating inflammatory parameters of TNF-α and IL-8.

Topics: Aged; Aged, 80 and over; Apoptosis; Biomarkers; Female; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Oxidative Stress; Peripheral Arterial Disease; Risk Factors; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

In recent years, the scientific publications about disorder the scientific publications appeared concerning derangement of content of alpha-defensins in neutrophils of patients with atherosclerosis. The interest increases both to different derangement of protein-synthesizing function of neutrophils and to biological effects caused by defensins and other peptides and proteins taking part in anti-microbial defense of human organism. With purpose to study content of alpha-defensins (1-3) and synthesis and liberation of other proteins and peptides by neutrophils the concentrations of alpha-defensins, lipoprotein (alpha), C-reactive protein, precursor of cerebral natriuretic peptide, coagulation factor VII and von Willebrand factor were determined in supernatants of leukocytal cultures in patients with exertional angina pectoris and atherosclerosis of lower extremities. The evaluation of loading test was implemented in vitro with alpha-tumor necrosis factor in vitro. Simultaneously, serum concentrations of cytokines and pro-atherogenic proteins were analyzed. It is established that in patients with ischemic heart disease derangement of protein-synthesizing function of neutrophils is observed. The derangement is manifested in the form of decrease of synthesis of alpha-defensins, increase of synthesis of lipoprotein (alpha), precursor of cerebral natriuretic peptide, C-reactive protein and von Willebrand factor. The pathogenic role of alpha-tumor necrosis factor is established. The increase of concentration of interleukin-8 in blood serum is revealed.

Topics: Adult; Aged; alpha-Defensins; Angina Pectoris; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Factor VII; Female; Humans; Interleukin-8; Leukocytes; Lipoproteins, HDL; Male; Middle Aged; Neutrophils; Peripheral Arterial Disease; Tumor Necrosis Factor-alpha; von Willebrand Factor

Peripheral arterial diseases, the major complication of diabetes, can result in lower limb amputation. Since endothelial progenitor cells (EPCs) are involved in neovascularization, the aim of this study was to examine whether EPCs isolated from Wharton's jelly (WJ-EPCs) of the umbilical cord, a rich source of mesenchymal stem cells, could reduce ischemia-induced hind limb injury in diabetic mice. We evaluated the effects of WJ-EPC transplantation on hind limb injury caused by femoral artery ligation in mice with streptozotocin (STZ)-induced diabetes. We found that the ischemic hind limb in mice with STZ-induced diabetes showed decreased blood flow and capillary density and increased cell apoptosis and that these effects were significantly inhibited by an injection of WJ-EPCs. In addition, hypoxia-inducible factor-1α (HIF-1α) and interleukin-8 (IL-8) were highly expressed in transplanted WJ-EPCs in the ischemic skeletal tissues and were present at high levels in hypoxia-treated cultured WJ-EPCs. Moreover, incubation of the NOR skeletal muscle cell line under hypoxic conditions in conditioned medium from EPCs cultured for 16 h under hypoxic conditions resulted in decreased expression of pro-apoptotic proteins and increased expression of anti-apoptotic proteins. The inhibition of HIF-1α or IL-8 expression by EPCs using HIF-1α siRNA or IL-8 siRNA, respectively, prevented this change in expression of apoptotic-related proteins. Wharton's jelly in the umbilical cord is a valuable source of EPCs, and transplantation of these EPCs represents an innovative therapeutic strategy for treating diabetic ischemic tissues. The HIF-1α/IL-8 signaling pathway plays a critical role in the protective effects of EPCs in the ischemic hind limb of diabetic mice.

Topics: Animals; Apoptosis; Cell Hypoxia; Cell Movement; Cells, Cultured; Diabetes Mellitus, Experimental; Femoral Artery; Hindlimb; Human Umbilical Vein Endothelial Cells; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-8; Ischemia; Male; Mice; Mice, Inbred ICR; Muscle, Skeletal; Neovascularization, Physiologic; Peripheral Arterial Disease; Regional Blood Flow; Signal Transduction; Stem Cell Transplantation; Stem Cells; Transcriptional Activation; Wharton Jelly