Serum Hypoxia-inducible Factor-1α Research Articles

Association of serum HIF-1α levels with coronary artery calcification in patients of non-dialysis chronic kidney disease

Vascular calcification is the main cause of death in patients with chronic kidney disease (CKD). The study aims to investigate the risk factor affecting coronary artery calcification (CAC), and the relationship between serum hypoxia-inducible factor-1α (HIF-1α) levels and CAC in non-dialysis CKD patients. One hundred and twenty-three patients were selected in the final analysis. Spearman rank correlation analysis assessed the correlation between HIF-1α levels and CAC scores. Logistic regression analysis was utilized to assess potential risk variables associated with CAC. A ROC curve was drawn to analyze the diagnostic value of HIF-1α in non-dialysis CKD patients with CAC. Compared to the non-CAC group, the CAC group was older age, with a higher proportion of males, smokers, hypertension and diabetes, lower eGFR and HDL-C, and higher SBP and HIF-1α levels. As the HIF-1α levels went up, the proportion of patients with VC increased, as well as Agatston scores. Spearman rank correlation analysis showed that HIF-1α levels were positively correlated with VC and Agatston scores. Logistic regression analysis indicated that being male (OR = 0.242, P = 0.036), older age (OR = 1.093, P < 0.001), and increased HIF-1α levels (OR = 1.002, P = 0.025) were risk factors for the occurrence of CAC. Furthermore, ROC curve analysis determined that a HIF-1α cutoff value of 451.177 pg·mL-1 provided the best diagnostic value for non-dialysis CAC, with a sensitivity of 65.8% and a specificity of 80.9%. The prevalence of CAC is high in non-dialysis CKD patients, with old age and male gender being traditional risk factors for CAC occurrence. HIF-1α positively correlate with both CAC and VC, which can provide certain diagnostic values for non-dialysis CAC.

Hypoxia-inducible factor-1α is a biomarker for predicting patients with sepsis.

This study aimed to investigate the potential value of serum hypoxia-inducible factor-1α (HIF-1α) concentrations as a biomarker in patients with sepsis. The enrolled patients were divided into the following four groups: the intensive care unit (ICU) control group (n = 33), infection group (n = 29), septic nonshock group (n = 40), and septic shock group (n = 94). An enzyme-linked immunosorbent assay was used to measure serum HIF-1α concentrations on ICU admission. Clinical parameters and laboratory test results were also collected. Serum HIF-1α concentrations were significantly higher in the infection group, septic nonshock group, and septic shock group than in the ICU control group. Moreover, HIF-1α concentrations were associated with a better predictive ability for diagnosing sepsis than the Acute Physiology and Chronic Health Evaluation II score, procalcitonin concentrations, and lactate concentrations. Patients with sepsis and HIF-1α concentrations >161.14 pg/mL had a poor prognosis. Serum HIF-1α concentrations are a useful biomarker for the diagnosis of sepsis and predicting the prognosis of patients.

The association between serum hypoxia inducible factor-1α level and urothelial bladder cancer: A preliminary study.

We aim to evaluate the association between serum hypoxia inducible factor (HIF)-1α level and stage and grade of urothelial bladder cancer (UBC). A case-control study was conducted at Haji Adam Malik Hospital Medan, Indonesia. Inclusion criteria for case group was subject aged 18 years or older and diagnosed with UBC based on histopathological examination. Control group consisted of gender and age matched healthy subjects. Serum HIF-1α level was determined using ELISA method. Data was analyzed with chi square, Mann Whitney, and independent T tests. A total of 80 subjects were enrolled and divided into case and control groups equally. Most subjects were males with mean age of 69.65 years for case group and 68.25 years for control group. Most subjects had advanced primary tumor and lymph node stages. Only 30% subjects had metastasized UBC. Higher serum HIF-1α level was observed in case group (p < 0.001). Serum HIF-1α level was strongly associated with metastasis stage (p < 0.001), followed by lymph node (p = 0.005) and primary tumor (p = 0. 013) stages. Serum HIF-1α level was not associated with grading (p = 0.134). Serum HIF-1α level is associated with staging but not grading of UBC.

Predictive value of serum HIF-1α and VEGF for arrhythmia in acute coronary syndrome patients.

Percutaneous coronary intervention (PCI) has been widely used in the alleviation of myocardial ischemia in patients with acute coronary syndrome (ACS). However, the incidence of reperfusion arrhythmia (RA) after PCI is high, which seriously affects the prognosis of ACS patients. Therefore, this study aimed to study the predictive value of serum HIF-1α and VEGF levels before PCI for RA in ACS patients post PCI. A total of 200 ACS patients who underwent PCI were selected and divided into those with RA after PCI (RA, n = 93) and those without RA after PCI (non-RA, n = 107) according to Lown grade. Spearman correlation analysis was applied for the relationship between serum hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) levels and Lown grade. Patients with RA after PCI tended to have higher levels of creatine kinase muscle and brain isoenzyme (CK-MB), serum HIF-1α and VEGF before surgery. Low left ventricular ejection fraction (LVEF), high CK-MB, high serum VEGF and HIF-1α were risk factors for RA in ACS patients within 24 h after PCI. Receiver operating characteristic (ROC) analysis revealed that serum HIF-1α and VEGF levels could predict RA in ACS patients after PCI, and the combined detection could increase the sensitivity of single HIF-1α detection and the specificity of single VEGF detection. Lown grade was positively correlated with the serum HIF-1α and VEGF concentrations. In conclusion, serum HIF-1α and VEGF levels before PCI are risk factors for the occurrence of RA in ACS patients after PCI, and have certain predictive values for the occurrence of RA in ACS patients after PCI.

Changes in serum hypoxia-inducible factor-1α and erythropoietin in allergic rhinitis patients: Correlation with the Th inflammatory profile and disease comorbidities.

The balance between proinflammatory IFN-γ Th1 vs. the anti-inflammatory allergy-mediating IL-4-heralded Th2 reactions is pivotal in IgE-mediated allergic rhinitis (AR). Hypoxia-Inducible Factor (HIF)-1α is inducible by hypoxia and various cytokines. HIF-1α activates different anti-pathogen and allergic immune cells. This cross-sectional study assessed the changes in serum HIF-1α and its dependent erythropoietin (EPO) levels among hospital-characterized AR patients. Type of the immune reaction, Th1 vs. Th2, was stratified based on the calculated IL-4/IFN-γ direct ratio, after being measured using specific ELISA assays. 147 AR patients (83 males/64 females), and age-, BMI-, and gender-matched 24 healthy controls (13 males/11 females) were sequentially enrolled at ENT Unit, Prince Muteb General Hospital, Sakaka, Saudi Arabia. Measurement of serum parameters was carried out using specific ELISA assays. Contrary to the majority of previous publications, all controls and the majority of patients (n = 137/147) exhibited naive Th0 immune response. IFN-γ and HIF-1α levels were greater in controls than in patients (168.9 ± 173.9 vs 108 ± 94.5pg/mL; p<.012) and controls had a lower IL-4/IFN-ratio (2.439 ± 0.897 vs 3.33 ± 1.19; p<.001) than patients. The HIF-1α results disagree with earlier studies. Due to the wide inter-individual variations, serum IL-4 and EPO levels in controls were non-significantly higher than patients. Lower IL-4 levels (267.3 ± 79.95 vs 353.4 ± 320.6pg/mL; p < .01) and the ratio (2.814 ± 1.335 vs 3.431 ± 1.137; p < .05) were associated with obstructive sleep apnea. Lower ratio was also associated with inferior turbinate hypertrophy (3.051 ± 1.026 vs 3.787 ± 1.310; p < .001). EPO and IL-4 levels were lower in patients with deviated nasal septum (66.69 ± 26.81 vs 84.24 ± 61.5pg/mL; p < .021; and 299.5 ± 137.3 vs 391.1 ± 52.780pg/mL; p < .001, respectively). Significant correlations were found between the recorded levels and AR comorbidities. These results confirmed a pathogenic implication for HIF-1α and IFN-γ in AR that warranted future bigger and longitudinal studies.

Guhong Injection Alleviates Cerebral Ischemia-Reperfusion Injury via the PKC/HIF-1α Pathway in Rats.

Guhong injection (GHI) is a drug for ischemic stroke created by combining safflower, a traditional Chinese medicine, and aceglutamide, a Western medicine. In this study, we investigated the curative effect of GHI on cerebral ischemia–reperfusion (I/R) injury via the PKC/HIF-1α pathway in rats. Adult male Sprague Dawley rats were randomly divided into seven groups: sham-operated, middle cerebral artery occlusion (MCAO), GHI, nimodipine injection (NMDP), MCAO + LY317615 (PKC inhibitor), GHI + LY317615, and NMDP + LY317615. After establishing an MCAO rat model, we performed neurological deficit testing, 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay, Western blotting, and q-PCR to detect the brain damage in rats. Compared with the MCAO group, the GHI and GHI + LY317615 group showed neurological damage amelioration as well as decreases in serum hypoxia-inducible factor-1α (HIF-1α), protein kinase C (PKC), and erythropoietin levels; brain HIF-1α and inducible nitric oxide synthase protein expression; and brain HIF-1α and NOX-4 mRNA expression. These effects were similar to those in the positive control groups NMDP and NMDP + LY317615. Thus, our results confirmed GHI can ameliorate cerebral I/R injury in MCAO rats possibly via the PKC/HIF-1α pathway.

Effects of Spironolactone on Hypoxia-Inducible Factor-1α in the Patients Receiving Coronary Artery Bypass Grafting.

We explored the protective effect of spironolactone on cardiac function in the patients undergoing coronary artery bypass grafting (CABG) by determining serum hypoxia-inducible factor-1α (HIF-1α) before and after CABG. We used the propensity score matching method retrospectively to select 174 patients undergoing CABG in our hospital from March 2018 to December 2019. Of the 174 patients, 87 patients taking spironolactone for more than 3 months before CABG were used as a test group and other 87 patients who were not taking spironolactone as a control group. In all patients, serum HIF-1α and troponin I levels were determined before as well as 24 hours and 7 days after CABG, serum N-terminal probrain natriuretic peptide (NT-proBNP) level was determined before as well as 12, 24, and 36 hours after CABG, and electrocardiographic monitoring was performed within 36 hours after CABG. The results indicated that there were no significant differences in the HIF-1α level between the test group and the control group before and 7 days after CABG, but the HIF-1α level was significantly lower in the test group than that in the control group 24 hours after CABG (P < 0.01). The 2 groups were not significantly different in the troponin I level at any time point. There was no significant difference in the serum NT-proBNP level between the test group and the control group before CABG, but NT-proBNP (BNP) levels were all significantly lower in the test group than those in the control group at postoperative 12, 24, and 36 hour time points (all P <0.05). The incidence of postoperative atrial fibrillation was also significantly lower in the test group than that in the control group (P = 0.035). Spironolactone protects cardiac function probably by improving myocardial hypoxia and inhibiting myocardial remodeling.

Analysis of the influencing factors and nursing strategy for acute atelectasis after traumatic brain injury surgery.

Acute atelectasis is common after traumatic brain injury (TBI), but the related factors and treatment are still unclear. This study is to analyze the independent risk factors for acute atelectasis after TBI and propose an interventional nursing strategy, in order to correct respiratory function and improve the prognosis of patients. The clinical data of 93 patients with TBI admitted to our hospital from April 2015 to October 2019 were retrospectively analyzed. Clinical data were analyzed by single factor analysis, the cutoff value of influencing factors was obtained by receiver operating characteristic (ROC) curve analysis, and the influencing factors for acute atelectasis after TBI were examined by multi-factor logistic regression. Twenty-two patients (23.66%) were complicated with acute atelectasis during the observation period, while the remaining 71 patients (76.34%) did not have acute atelectasis. Univariate analysis showed that there were significant differences in the Glasgow Coma Scale (GCS), history of vomiting and aspiration, mannitol use, mechanical ventilation, hypoalbuminemia, and serum hypoxia-inducible factor-1α (HIF-1α) between the acute atelectasis group and the non-acute atelectasis group (P<0.05). The AUC area of HIF-1α level predicting acute atelectasis was 0.896 [95% confidence interval (CI): 0.814-0.978, P=0.042], and the cut-off value was 2.12 mmol/L, with a sensitivity of 76.9% and a specificity of 93.3%. Logistic regression analysis showed that a history of vomiting and aspiration [odds ratio (OR) 3.908, 95% confidence interval (CI): 1.201-12.712], mechanical ventilation (OR 3.250, 95% CI: 1.139-9.271), hypoalbuminemia (OR 5.741, 95% Cl: 1.926-17.113), and HIF-1α ≥2.12 mmol/L (OR 6.623, 95% CI: 2.364-16.346) were independent risk factors for acute atelectasis after TBI. A history of vomiting and aspiration, mechanical ventilation, hypoalbuminemia, and high expression of HIF-1α are all independent risk factors for postoperative acute atelectasis in patients with TBI. In clinical practice, patients should be guided to swallow properly, breathe smoothly, eat well, and regularly check the relevant indexes.

Maxingxiongting mixture attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the rho-kinase signaling pathway.

To explore the mechanism of Maxingxiongting mixture (MXXTM) on pulmonary hypertension in a rat model established by intraperitoneal injection of monocrotaline solution, smoking and forced swimming. A total of 30 male Sprague-Dawley rats were randomly divided into five groups: control group, model group, high-dose of MXXTM group (HM), low-dose of MXXTM group (LM), and fasudil group. The mean pulmonary artery pressure (mPAP) was measured by using a miniature catheter. Lung tissue and right ventricular tissue sections were stained with hematoxylin-eosin. The right ventricle (RV) and left ventricle + septum (LV + S) were weighted. RV/(LV+S) was calculated to reflect the degree of right ventricular hypertrophy. Rho/Rho-kinase signaling pathway key proteins (RhoA, ROCK Ⅰ and ROCK Ⅱ) in rat right ventricular tissue were measured by Western blot analysis. The levels of serum hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and the levels of plasma renin activity (PRA), angiotensin Ⅱ (ANG-Ⅱ), aldosterone (ALD) in rat anticoagulated plasma were all measured by enzyme-linked immunosorbent assay. Compared with the control group, the mPAP and RV/(LV+S) in the model group were significantly increased. Administration of fasudil resulted in a significant decrease of mPAP and RV/ (LV+S). In the HM group and LM group, mPAP and RV/ (LV+S) were significantly lower than the model group. Compared with the control group, the contents of HIF-1α, VEGF, PRA, ANG-Ⅱ and ALD in the model group were significantly increased. The administration of fasudil and high-dose MXXTM significantly reduced the contents of HIF-1α, VEGF, PRA, ANG-II and ALD. Compared with the control group, the expression of RhoA, ROCK Ⅰ and ROCK Ⅱ in the right ventricle of the model group were significantly increased. The administration of fasudil and high-dose MXXTM significantly reduced the expression of RhoA and Rock Ⅱ proteins. Our results indicated that high-dose of MXXTM had similar effects on reducing pulmonary artery pressure and improving right ventricular remodeling to fasudil. However, MXXTM was unable to restore parameters above to control levels. MXXTM attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the Rho-kinase signaling pathway.

Expression and predictive value of HIF-1α and VEGF in patients with burns following treatment.

The present study aimed to investigate the expression and predictive value of serum hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in patients with burns following treatment. A total of 84 patients with burns treated in Jinan City People's Hospital (Jinan, China) between June 2015 and August 2017 were selected and their clinical information was collected. The expression levels of HIF-1α and VEGF before and after treatment were detected via ELISA, and HIF-1α and VEGF levels in patients with effective and ineffective treatment were compared. The predictive values of HIF-1α and VEGF in clinical efficacy were determined using receiver operating characteristic (ROC) curves, and independent risk factors affecting treatment inefficacy were analyzed via multivariate logistic regression. It was revealed that HIF-1α decreased significantly (P<0.05) while VEGF significantly increased in patients after treatment. Patients with effective treatment presented significantly lower HIF-1α levels and higher VEGF levels compared with those with ineffective treatment. The ROC curve indicated that the area under the curve (AUC) of HIF-1α for treatment efficacy was 0.795, the 95% CI was 0.666-0.924, the specificity and sensitivity were 68.75 and 80.88%, respectively, and the Youden index was 49.63%. For VEGF, the AUC, 95% CI, specificity, sensitivity and Youden index were 0.826, 0.725-0.928, 68.75, 82.35 and 51.10% respectively. Moreover, under the joint detection of HIF-1α and VEGF, the AUC was 0.847, 95% CI was 0.746-0.947, specificity and sensitivity were 87.50 and 66.18%, respectively, with a Youden index of 53.68%. Multivariate analysis demonstrated that higher HIF-1α level, lower VEGF level and higher burn degree before treatment were independent risk factors for treatment inefficacy. HIF-1α levels decreased and VEGF levels increased in burn patients after treatment. HIF-1α and VEGF before treatment may therefore serve as predictors for treatment efficacy.

Serum hypoxia-inducible factor-1α protein level as a diagnostic marker of obstructive sleep apnea.

Serum hypoxia-inducible factor-1α protein level as a diagnostic marker of obstructive sleep apnea.

Therapeutic effect of high‐frequency ultrasound‐assisted dye laser on hemangioma and its influence on serum HIF‐1α in patients

BackgroundTo analyze the therapeutic effect of high‐frequency ultrasound (HFU)‐assisted dye laser on hemangioma patients and changes in serum hypoxia‐inducible factor‐1α (HIF‐1α).MethodsA total of 20 patients diagnosed with hemangioma in our hospital from January 2013 to March 2018 were selected, including 12 males and eight females. All patients were treated with HFU‐assisted dye laser. The site and type of hemangioma and age distribution of patients were collected, and changes in data and area of hemangioma and serum HIF‐1α before and after treatment were analyzed.ResultsThe vascular condition of hemangioma in all patients was significantly improved at 7, 14, and 30 days after treatment. Gray‐scale ultrasound displayed that the tumor area was reduced by more than 50%. After treatment, the serum HIF‐1α level declined obviously after treatment compared with that before treatment, showing a statistically significant difference (P < 0.05).ConclusionHFU‐assisted dye laser can effectively reduce the tumor area, decrease the serum HIF‐1α level, and improve the prognosis in the treatment of hemangioma.

Evaluation of maternal serum hypoxia inducible factor-1α, progranulin and syndecan-1 levels in pregnancies with early- and late-onset preeclampsia

Objective: To determine the serum levels of HIF-1 α, progranulin, and syndecan-1 in preeclampsia (PE) and normal pregnancy, and to compare whether these markers demonstrate any difference between early-onset PE (EO-PE) and late-onset PE (LO-PE).Methods: This cross-sectional study was conducted on 27 women with EO-PE, 27 women with LO-PE, and 26 healthy normotensive pregnant controls matched for gestational age. Maternal levels of serum HIF-1 α, progranulin, and syndecan-1 were measured with the use of an enzyme-linked immunosorbent assay kit.Results: Statistical analysis revealed significant differences between the control and the PE groups in progranulin (p < .001) and syndecan-1 (p <.001) levels. There were no significant differences in the serum HIF-1 α levels between these groups (p= .069). When PE patients were evaluated by considering subgroups; statistical analysis revealed significant inter-group differences in all biomarkers. Serum progranulin levels were significantly higher in LO-PE compared with the other two groups (EO-PE versus LO-PE and LO-PE versus controls p = .000). Control group presented significantly higher syndecan-1 levels, than EO and LO-PE (p < .001). HIF-1 α levels positively correlated with progranulin levels (r = .439, p= .000).Conclusions: Serum progranulin may have potential to be used as a biomarker for the differentiation of EO-PE and LO-PE. The co-operative action between HIF-1 α and progranulin might play a key role in the pathogenesis of LO-PE. The predominant feature of LO-PE seems to be an inflammatory process, whereas in EO-PE placentation problem seems to be the main pathology.

Elevated concentrations of hypoxia-inducible factor-1α in patients with fracture and concomitant traumatic brain injury.

Background Compelling evidence indicate that traumatic brain injury is highly related to accelerated bone fracture repair, but the underlying mechanism still remains elusive. Fracture repair process relies greatly on the formation of new blood vessels in fracture site, and angiogenic factors have been confirmed to be essential for the initiation and maintenance of the fracture healing. Hypoxia-inducible factor-1α was demonstrated to be a critical regulator of angiogenic-osteogenic coupling during bone development and regeneration. The aim of the present study was to investigate the local and circulating concentrations of hypoxia-inducible factor-1α in patients with long-bone fractures and concomitant traumatic brain injury and to determine the potential role of hypoxia-inducible factor-1α in fracture healing. Methods Twenty-five patients with a long-bone fracture and concomitant traumatic brain injury (FT group) and 33 without a brain injury (Fr group) were enrolled in this study. Healthy subjects donated serum samples as control. Serum samples were collected over a period of six months, following a standardized time schedule. Hypoxia-inducible factor-1α concentrations were measured in fracture haematoma and serum of patients in both groups using enzyme-linked immunosorbent assay. Results Patients in FT group had a short time to union. Serum hypoxia-inducible factor-1α concentrations elevated in the early healing period and reached the maximum level during intramembranous bone formation phase in both groups. Thereafter, it decreased continuously and approached to the minimum levels until the end of the observation period. Serum hypoxia-inducible factor-1α concentrations in both groups were significantly higher compared with controls and hypoxia-inducible factor-1α concentrations in both serum and fracture haematoma were higher in FT group than that in Fr group. Fracture haematoma contained significantly higher hypoxia-inducible factor-1α concentrations compared with hypoxia-inducible factor-1α concentrations in serum. Serum hypoxia-inducible factor-1α concentrations had a positive correlation with hypoxia-inducible factor-1α concentrations in fracture haematoma in patients with fractures. Conclusions These findings suggest the local and systemic involvement of hypoxia-inducible factor-1α in fracture healing and the accelerated fracture repair in patients with traumatic brain injury might be associated with elevated hypoxia-inducible factor-1α concentrations in fracture haematoma and serum.

Effect of rapamycin on endometriosis in mice.

The aims of the present study were to investigate the impact of rapamycin (RAPA) on the endometriosis (EMS) lesions in severe combined immunodeficiency (SCID) mice, and to examine the possible mechanism involved in a novel therapy in EMS. Following the successful establishment of an EMS-SCID mouse model, the mice were randomly assigned into the RAPA, control and saline treatment groups. Subsequent to treatment for 2 weeks, the serum hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected using ELISA. The levels of HIF-1α and VEGF, as well as the size of EMS lesions, were compared among the three groups. In addition, the HIF-1α, VEGF and CD34 protein expression levels, and the microvessel density (MVD) of the lesions were determined by immunohistochemical analysis. Compared with the control and saline groups, the volume of EMS lesions in the RAPA-treated SCID mice was significantly reduced. Furthermore, the serum level and protein expression of VEGF, and the MVD in the lesions of the RAPA-treated group were significantly reduced when compared with the other two groups. These parameters were comparable in the control and saline groups. In conclusion, RAPA may inhibit the growth of endometriotic lesions, most possibly through the inhibition of the expression of VEGF in lesions, thereby inhibiting angiogenesis.

Regulating Effect Of Carnosine And /Or L- Arginine On The Expression Of Inflammatory Molecules Induced Nephropathy In The Hypoxic Rat Model

This study aimed to explore the effective role of carnosine and /or L- arginine in down regulation of the inflammatory molecule expression caused renal damage in response to sodium nitrite (NaNO2) induced hypoxia in rats . NaNO2 was administered subcutaneously (s.c.) to rats as a single dose (60 mg/kg body weight ). L-arginine (200mg/Kg body weight) and carnosine (250 mg/ Kg body weight ) were administered (i.p.) as a single dose , 24 h before NaNO2 injection. The results revealed that pre- administration of arginine and /or carnosine to NaNO2 hypoxic rats, significantly modulated the increases in serum markers of renal function (creatinine and urea) as well as the decrease in hemoglobin (Hb) level versus hypoxic rats. The two agents each alone or in a combination, markedly down regulated the serum pro-inflammatory molecules, including tumor necrosis factor-α (TNF- α) , C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and heat shock protein -70 (HSP-70) as well as interleukin-6 (IL-6) in renal tissue compared to NaNO2 hypoxic rats . Also, the two agents successfully down modulated the alteration in the serum hypoxia inducible factor 1α (HIF 1α) . The present biochemical results were also supported by histopathological examination. In conclusion, the current data revealed that although the efficacy of arginine or carnosine each alone, their combination was more effective in ameliorating the renal damage induced by inflammatory molecules in response to NaNO2 hypoxia . This may support the use of this combination as an effective drug to treat hypoxic renal damage

Levels of Serum 25(OH)VD3, HIF-1α, VEGF, vWf, and IGF-1 and Their Correlation in Type 2 Diabetes Patients with Different Urine Albumin Creatinine Ratio.

Objective. To investigate changes in serum 25(OH)VD3, HIF-1α, VEGF, vWf, IGF-1, and their correlation in type 2 diabetes patients at different stages of diabetic kidney disease (DKD). Methods. 502 type 2 diabetes patients were divided into three groups: Normoalbuminuric group (201 patients), Microalbuminuric group (171 patients), and Macroalbuminuric group (130 patients). Serum 25-hydroxyvitamin D3 [25(OH)VD3] was measured by chemiluminescence. Serum hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), von Willebrand factor (vWf), and insulin-like growth factor-1 (IGF-1) were determined by enzyme-linked immunosorbent assay. We detected the aforementioned serum factors in all cases and 224 control subjects. Results. Serum HIF-1α, VEGF, vWf, and IGF-1 in type 2 diabetes patients were significantly higher than those in the control group and increased with the increase of Ln(ACR), respectively (P < 0.001). Serum 25(OH)VD3 was significantly lower in type 2 diabetes patients and decreased with the increase of Ln(ACR) (P < 0.001). Ln(ACR) was positively correlated with duration, HbA1c, Scr, BUN, TC, LDL, TG, UA, HIF-1α, VEGF, IGF-1, vWf, and Fg and negatively correlated with 25(OH)VD3 and eGFR. Conclusion. Serum HIF-1α, VEGF, vWf, and IGF-1 may be involved in DKD process through inflammation, angiogenesis, and endothelial injury. Serum 25(OH)VD3 may have protective effects on DKD partly by inhibiting inflammation, abnormal angiogenesis, and vascular endothelial dysfunction.

Clinical Implications of Serum Hypoxia Inducible Factor-1α and Vascular Endothelial Growth Factor in Lung Cancer

Hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) have been deemed as key in angiogenesis of lung cancer. The aim of this study was to investigate diagnostic and prognostic values of HIF-1α and VEGF in patients with lung cancer. From May 1, 2011, to April 20, 2014, blood samples and/or pleural effusions were collected from 100 patients with lung cancer, 18 patients with tuberculosis, 47 patients with community-acquired pneumonia, and 29 healthy controls. The pretreatment levels of HIF-1α and VEGF were measured by enzyme-linked immunoassays. Patients with lung cancer were followed up during the period of this study and survival times were recorded for analysis. We detected that the levels of serum and pleural HIF-1α in lung cancer were significantly higher than those in the tuberculosis population, and that the VEGF expressions were not significantly different between malignancy and benign diseases. An area under the curve of pleural HIF-1α (0.877 ± 0.053) showed a high ability to differentiate lung cancer from benign diseases. The significant negative predictors of survival in the univariate analysis were performance status (gt;1), no anticancer therapy, low serum albumin, advanced stage, and serum high level of VEGF (gt;324.17 pg/mL), while in the multivariate Cox regression analysis, only the pretreatment serum level of VEGF, stage, and anticancer therapy were identified as independent prognostic factors. The overexpression of HIF-1α especially in pleural effusion may be an angiogenic factor for distinguishing malignancy from tuberculosis, and the pretreatment level of serum VEGF may be an independent predictor of survival.

The relationship between serum hypoxia-inducible factor 1α and coronary artery calcification in asymptomatic type 2 diabetic patients

BackgroundHypoxia-inducible factor 1 (HIF-1), a master regulator of oxygen homeostasis, is a heterodimer consisting of HIF-1α and HIF-1β subunits, and is implicated in calcification of cartilage and vasculature. The goal of this study was to determine the relationship between serum HIF-1α with coronary artery calcification (CAC) in patients with type 2 diabetes.MethodsThe subjects were 405 (262 males, 143 females, age 51.3 ± 6.4 years) asymptomatic patients with type 2 diabetes mellitus. Serum HIF-1α and interleukin-6 (IL-6) levels were measured by ELISA. CAC scores were assessed by a 320-slice CT scanner. The subjects were divided into 4 quartiles depending on serum HIF-1α levels.ResultsAverage serum HIF-1α was 184.4 ± 66.7 pg/ml. Among patients with higher CAC scores, HIF-1α levels were also significantly increased (p <0.001). HIF-1α levels positively correlated with CRP, IL-6, UKPDS risk score, HbA1c, FBG, and CACS, but did not correlate with diabetes duration, age, and LDL. According to the multivariate analysis, HIF-1α levels significantly and independently predict the presence of CAC. ROC curve analysis showed that the serum HIF-1α level can predict the extent of CAC, but the specificity was lower than the traditional risk factors UKPDS and HbA1c.ConclusionAs a marker of hypoxia, serum HIF-1α level may be an independent risk factor for the presence of CAC. These findings indicate that elevated serum HIF-1α may be involved in vascular calcification in patients with type 2 diabetes mellitus.

A Randomly-Controlled Study on the Cardiac Function at the Early Stage of Return to the Plains after Short-Term Exposure to High Altitude

High altitude acclimatization and adaptation mechanisms have been well clarified, however, high altitude de-adaptation mechanism remains unclear. In this study, we conducted a controlled study on cardiac functions in 96 healthy young male who rapidly entered the high altitude (3700 m) and returned to the plains (1500 m) after 50 days. Ninety eight healthy male who remained at low altitude were recruited as control group. The mean pulmonary arterial pressure (mPAP), left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), cardiac function index (Tei index) were tested. Levels of serum creatine kinase isoform MB (CK-MB), lactate dehydrogenase isoenzyme-1 (LDH-1), endothelin-1 (ET-1), nitrogen oxide (NO), serum hypoxia-inducible factor-1α (HIF-1α), 8-iso-prostaglandin F2α (8-iso PGF2α), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at an altitude of 3700 m and 1500 m respectively. The results showed that after short-term exposure to high altitude mPAP and Tei index increased significantly, while LVEF and LVFS decreased significantly. These changes were positively correlated with altitude. On the 15th day after the subjects returned to low altitude, mPAP, LVEF and LVFS levels returned to the same level as those of the control subjects, but the Tei index in the returned subjects was still significantly higher than that in the control subjects (P<0.01). We also found that changes in Tei index was positively correlated with mPAP, ET-1, HIF-1α and 8-iso PGF2α levels, and negatively correlated with the level of NO, LVEF, LVFS, CK-MB and LDH-1. These findings suggest that cardiac function de-adapts when returning to the plains after short-term exposure to high altitude and the function recovery takes a relatively long time.