CIDEC silencing attenuates diabetic nephropathy via inhibiting apoptosis and promoting autophagy.

OBJECTIVE: The role of cell death-inducing DFF45-like effector C (CIDEC) in insulin resistance has been established, and it is considered to be an important trigger factor for the progression of diabetic nephropathy (DN). We intend to explore whether CIDEC plays an important role in the regulation of DN and its potential mechanism. METHODS: High-fat diet and low dose streptozotocin were used to establish type 2 diabetic rat model. We investigate the role of CIDEC in the pathogenesis and process of DN through histopathological analysis, western blot and gene silencing. Meanwhile, the effect of CIDEC on renal tubular epithelial cells stimulated by high glucose was also verified. RESULTS: DM group exhibited glucose and lipid metabolic disturbance, with hypertrophy of kidneys, damaged renal function, increased apoptosis, decreased autophagy, glomerulosclerosis and interstitial fibrosis. CIDEC gene silencing improved metabolic disorder and insulin resistance, alleviated renal hypertrophy and renal function damage, decreased glomerular and tubular apoptosis, increased autophagy and inhibited renal fibrosis. At the cellular level, high glucose stimulation increased CIDEC expression in renal tubular epithelial cells, accompanied by increased apoptosis and decreased autophagy. CIDEC gene silencing can improve autophagy and reduce apoptosis. At the molecular level, CIDEC gene silencing also decreased the expression of early growth response factor (EGR)1 and increased the expression of adipose triglyceride lipase (ATGL). CONCLUSION: CIDEC gene silencing may delay the progression of DN by restoring autophagy activity and inhibiting apoptosis with the participation of EGR1and ATGL.

High molecular weight fibroblast growth factor-2 as a promising prognostic biomarker to predict the occurrence of heart failure in atrial fibrillation patients.

Heart failure (HF) has a significant effect on the prognosis of the patients with atrial fibrillation (AF), and also it is an important risk factor for overall mortality. High molecular weight fibroblast growth factor-2 (Hi-FGF-2) is emerging as a prognostic marker with HF and AF. The aim of this study was to prove that Hi-FGF-2 would predict occurrence of HF in the patients with AF. Subjects diagnosed with paroxysmal AF (Group paAF), persistent AF (Group peAF) and sinus rhythm (Group SR) were enrolled in the study. Serum Hi-FGF-2 concentration was measured by ELISA at baseline. Multivariable logistic models and receiver operating characteristic (ROC) curve analysis were established to predict the prognosis of AF subjects. 260 patients were enrolled in the study: 104 (40.0%) admitted for sinus rhythm (Group SR) and 156 (60.0%) with AF (Group paAF and Group peAF). The Hi-FGF-2 levels were much lower in the Group SR (58.2 ± 27.1 ng/L) than in the Group AF. Furthermore, the Group peAF (84.3 ± 34.1 ng/L) had higher Hi-FGF-2 levels than the Group paAF (72.9 ± 35.8 ng/L). Serum Hi-FGF-2 levels were classified into trisection in the multivariable logistic model (T1 < 57.3 ng/L, 57.3 < T2 < 86.5 ng/L, and T3 > 86.5 ng/L). Hi-FGF-2 showed good predictive ability for new-onset HF in the patients with AF. The occurrence of HF was associated significantly with increased tertile of serum Hi-FGF-2 levels (T2: OR 5.922, 95% CI 1.109-31.626, P = 0.037 and T3: OR 8.262, 95% CI 1.735-39.343, P = 0.008). ROC curve analysis showed that the area under curves for Hi-FGF-2 were 0.720 (P < 0.0001). Hi-FGF-2 has a significant meaning in AF subjects. Further to this, higher circulating Hi-FGF-2 was highly related to persistent AF, and Hi-FGF-2 may be an independent risk factor of occurrence HF in AF subjects.

Potential Roles of Serum Caveolin-3 Levels in Patients with Atrial Fibrillation.

Objective: To explore serum caveolin-3 (Cav-3) levels in patients with atrial fibrillation (AF) and to evaluate the role of Cav-3 as a biomarker for AF and incident heart failure (HF). Methods: Three hundred and five patients were enrolled in the study and divided into three groups: sinus rhythm (Group SR), paroxysmal AF (Group paAF), and persistent AF (Group peAF). Serum Cav-3 concentrations were measured by enzyme-linked immunosorbent assay at baseline. Clinical characteristics, and laboratory data were collected during hospitalization, and a follow-up of 12-months was carried out. Results: Serum Cav-3 concentrations were significantly decreased on the Group SR and the highest concentrations of Cav-3 in patients were found on the Group peAF (516.7 ± 274.0 vs. 609.3 ± 287.0 vs. 688.3 ± 264.6 ng/L, P < 0.05). Left atrial diameter (LAD) in the Group peAF was significantly higher than in the Group paAF, and the Group SR had significantly lower LAD than the Group paAF and Group peAF. The risks of new-onset HF in the Group SR, Group paAF, and Group peAF were 8.1, 14.5, and 28.6%, respectively. There was a significant difference between the Group peAF and the other two groups. Serum Cav-3 concentrations were trisected in AF participants (lower tertile: ≤498, middle tertile: >498-703, upper tertile: ≥703). In further tertile studies, subjects in the lower tertile of Cav-3 concentrations were more likely to become paroxysmal AF and had much lower LAD (P < 0.05). And in the middle and upper tertiles, participants with AF tended to suffer from HF compared to the lower group (P < 0.05). Conclusion: We provide evidence that Cav-3 has a significant meaning in AF patients. The levels of Cav-3 may be related to the LAD and new-onset HF.

[Ixeris sonchifolia induced vasoconstriction effect and its mechanism in rat thoracic aorta].

OBJECTIVE: To investigate the vasoconstriction effect of Ixeris sonchifolia in rat thoracic aortic rings and the underlying mechanisms. METHOD: I. sonchifolia 10-160 g x L(-1) was cumulatively added into organ bath to observe the isometric tension of thoracic aortic rings with intact endothelium or denuded endothelium in basal tension, preconstricted by phenylephrine (PE) or potassium chloride (KCl), and thoracic aortic rings with intact endothelium preincubated frist with captopril, phosphoramidon and indomethacin, respectively, then preconstricted by PE and KCl. The response was recorded and expressed by "relative contraction". RESULT: Cumulative administration of I. sonchifolia 10-160 g x L(-1) did not affect the vasomotion of aortic rings with endothelium or without endothelium in basal tension. Exposure of intact endothelium rings preconstricted by PE or KCl to I. sonchifolia at concentration (20-160 g x L(-1) induced a significant constriction, which was inhibited by preincubation with captopril, but was not inhibited by preincubation with phosphoramidon or indomethacin. Exposure of endothelium-denuded rings preconstricted by PE or KCl to I. sonchifolia at concentration (10 to approximately 160 g x L(-1) did not effect the vasoconstriction. CONCLUSION: The results indicate that I. sonchifolia (20 to approximately 160 g x L(-1) can contract the rat thoracic aortic rings with endothelium. The effect of contraction may enhance angiotensin converting enzyme activity and promote endothelium to synthesize angiotensin II. It has no relationship to endothelin or thromboxane A2.