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Increased plasma and adipose tissue levels of ANGPTL8/Betatrophin and ANGPTL4 in people with hypertension

Posted by M Abu-Farha, P Cherian, D Sriraman, et al. on 2018-03-14 19:52:52

Abstract

Background

Hypertension is a risk factor for both cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Angiopoietin-like proteins (ANGPTLs), mainly ANGPTL3, ANGPTL4 and ANGPTL8, are associated with increased plasma lipid content due to their role in regulating the activity of lipoprotein lipase, a key enzyme in metabolism of the lipoprotein in circulation. Dyslipidaemia is a risk factor for hypertension development; however, the roles of ANGPTL3, ANGPTL4 and ANGPTL8 in subjects with hypertension have not yet been established. This study compared the plasma and adipose tissue levels of ANGPTL3, ANGPTL4 and ANGPTL8 in age- and body mass index-matched subjects with and without hypertension.

Methods

A total of 119 subjects, including 69 hypertensive and 50 non-hypertensive subjects, were enrolled. ANGPTL3, ANGPTL4 and ANGPTL8 plasma levels were measured by ELISA, whereas their levels in adipose tissue were assessed via real-time PCR.

Results

We found that ANGPTL4 (202.49 ± 17.44 ng/mL vs. 160.64 ± 10.36 ng/mL, p = 0.04) and ANGPTL8 levels (2310.96 ± 194.88 pg/mL vs. 1583.35 ± 138.27 pg/mL, p = 0.001) were higher in hypertensive subjects than non-hypertensive subjects. However, ANGPTL3 levels were not significantly different between the two populations. Similarly, ANGPTL4 and ANGPTL8 levels were also elevated in subjects with T2D and hypertension than in those with T2D but not hypertension. Additionally, people with highest tertiles of ANGPTL8 had higher odds of having hypertension (odd ratio [OR] = 3.8, 95% confidence interval [CI] = (1.5-9.8), p-Value = 0.005. Similar to its plasma levels, ANGPTL4 and ANGPTL8 were higher in adipose tissue.

Conclusions

In conclusion, our data illustrate that ANGPTL4 and ANGPTL8 levels in both plasma and adipose tissues are increased in subjects with hypertension. The elevated levels of ANGPTL4 and ANGPTL8 in hypertensive subjects highlight their potential involvement, their potential role as biomarkers for hypertension and their therapeutic value in hypertension given their roles in regulating lipid metabolism.

Keywords

Hypertension Angiopoietin-like proteins Type-2 diabetes

HIF-1A gene polymorphisms and its protein level in patients with rheumatoid arthritis: a case–control study

Posted by B Stypinska, A Pawlik, E Haladyj, et al. on 2018-02-26 22:09:12

Abstract

Objectives

The aim of the study was to identify HIF-1A genetic variants and their possible association with HIF-1alpha, VEGF, KDR, RORc and Foxp3 protein levels, and susceptibility to and severity of RA.

Methods

The HIF-1A gene polymorphisms were genotyped for 587 RA patients and 341 healthy individuals. The HIF-1alpha, VEGF, KDR, RORc and Foxp3serum levels were evaluated.

Results

Under the codominant model, the frequency of the rs12434438 GG genotype was lower in RA patients than in controls (P = 0.02). Under the recessive model (AA + AG vs GG), the association was also significant (OR 3.32; CI 1.19–9.24; P = 0.02). Overall, rs12434438 A/G and rs1951795 A/C are in almost completed linkage disequilibrium with D = 0.96 and r2 = 0.85. The HIF-1A rs1951795 A allele was associated with rheumatoid factor (P = 0.02) and mean value of erythrocyte sedimentation rate (ESR) (P = 0.05). In RA patients with HIF-1A rs12434439 GG genotype, the parameters of disease activity such as DAS-28, VAS score, Larsen score or HAQ score were lower compared to RA patients with the HIF-1A rs12434439 AA genotype. Moreover, we also observed that Foxp3 serum levels were higher, and RORc2 serum levels were lower in RA patients with rs12434439 GG.

Conclusion

The polymorphic HIF-1A rs12434439 GG genotype may play a protective role for RA development.

Keywords

Gene polymorphisms Rheumatoid arthritis HIF-1alpha Angiogenesis Inflammation

Abstract

Objectives

Vitamin D-binding protein (VDBP), retinol-binding protein (RBP)4, and heat shock proteins (hsp) are markers of tubular function and apoptosis, accompanying chronic kidney disease (CKD) from its earliest stages. Fractional excretion of proteins with urine is a marker of tubular damage. The aim of study was to assess the usefulness of fractional excretion (FE) of VDBP, RBP4, HSF1 and Hsp27 as markers of tubular damage in the course of CKD.

Methods

The study group consisted of 70 children with CKD stages 1–5, treated conservatively, and 12 age-matched controls with normal kidney function. The serum and urine concentrations of VDBP, RBP4, HSF1 and Hsp27 were assessed by ELISA. The fractional excretion of analyzed parameters was calculated according to the formula: ([parameter urine concentration]?×?[creatinine serum concentration])?/?([parameter serum concentration]?×?[creatinine urine concentration])×100%.

Results

The FE values of all parameters exceeded 1% in CKD stage 2. However, the values of FE have raised significantly versus control group no sooner than CKD stage 2 (RBP4 and HSF1), stage 3 (VDBP) or stage 4 (Hsp27).

Conclusion

Fractional excretion of RBP4 and HSF1 with urine may become a valuable marker, assessing the damage of tubular cells in children with CKD.

Abstract

Objective

The study covers an evaluation of the influence of extracts (1–50 μg/ml), isolated from aerial parts of nine Trifolium L. species (i.e. T. alexandrinum, T. fragiferum, T. hybridum, T. incarnatum, T. pallidum, T. pratense, T. resupinatum var. majus, T. resupinatum var. resupinatum and T. scabrum) on haemostatic properties of blood plasma.

Methods

The clot formation and fibrinolysis assay (CFF), blood clotting times, the extrinsic and intrinsic coagulation pathway-dependent polymerization of plasma fibrin were measured. The effects of plant extracts on amidolytic activity of thrombin were also evaluated and compared with argatroban, an antithrombotic drug. Cytotoxicity was assessed in a model of blood platelets and as the viability of peripheral blood mononuclear cells.

Key findings

While no changes in blood clotting times or fibrinolytic properties of blood plasma were found, some fractions impaired the blood plasma coagulation induced by the intrinsic coagulation pathway. Reduction in the maximal velocity of fibrin polymerization was also observed in the clot formation and fibrinolysis assay. No cytotoxicity of Trifolium extracts towards the investigated cells was recorded.

Conclusions

The most efficient anticoagulant activity in plasma was found for T. fragiferum and T. incarnatum extracts, while the T. alexandrinum fraction was the most effective inhibitor of thrombin amidolytic activity.

Dexmedetomidine and Magnesium Sulfate: A Good Combination Treatment for Acute Lung Injury?

Posted by E Dogan, M Kuyumcu, F Celik, et al. on 2018-01-30 22:21:55

ABSTRACT

Objectives: In this study, we aimed to investigate the therapeutic effects of magnesium sulfate (MgSO4) and dexmedetomidine (dex) in a model of acute lung injury (ALI). We determined whether concomitant administration decreased the inflammatory effects of hydrochloric acid (HCl)-induced ALI in a synergistic manner. Materials and Methods: In this study, 42 Sprague–Dawley rats were randomized into six groups: Group S (saline), Group SV (saline + mechanical ventilation), Group HCl (HCl), Group Dex (Dex), Group Mag (MgSO4), and Group DM (Dex + MgSO4). All groups except Group S were mechanically ventilated prior to HCl-induced ALI. Saline or HCl was administered via tracheostomy. Prior to treatment, HCl was administered to Group HCl, Group Dex, Group Mag, and Group DM to induce ALI. Dex and MgSO4 were administered intraperitoneally. The rats were monitored for 4 h after treatment to measure oxidative stress parameters in blood, and prolidase enzyme activity. Lung tissue damage were determined via histopathology. Results: A significant increase in heart rate and rapid desaturation was observed in HCl-administered groups. Treatment administration decreased the pulse values. Increased saturation values and decreased oxidative stress indices were observed in groups that were subsequently administered Dex and MgSO4. Serum prolidase activity increased significantly in Group HCl. Severe pathological findings were detected following HCl-induced ALI. Group Mag showed greater improvement in the pathology of HCl-induced ALI than did Group Dex. Administration of both Dex and MgSO4 did not improve the pathological scores. Conclusions: The antioxidant and anti-inflammatory effects of Dex and MgSO4 ameliorated the detrimental effects of HCI-induced ALI. However, adverse effects on hemodynamics and lung damage were observed when the two drugs were administered together.

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