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- Title
Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats.
- Authors
Jing-Yue XU; Zheng-Kai XUE; Ya-Ru ZHANG; Xing LIU; Xue ZHANG; Xi YANG; Tong LIU; Kang-Yin CHEN
- Abstract
BACKGROUND Chronic renal failure (CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia (VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process. METHODS A total of 48 rats were randomly divided into sham operation group (Sham group), CRF group, CRF + atorvastatin group (CRF + statin group), and CRF + etanercept group (CRF + rhTNFR-Fc group). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43 (GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay. RESULTS Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay, immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fc group. CONCLUSIONS In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.
- Subjects
CHRONIC kidney failure complications; HEART analysis; HEART anatomy; MUSCLE analysis; KIDNEY physiology; LEFT heart ventricle; T-test (Statistics); RESEARCH funding; VENTRICULAR remodeling; ENZYME-linked immunosorbent assay; BODY weight; SYMPATHETIC nervous system; FLUORESCENT antibody technique; VENTRICULAR fibrillation; NEPHRECTOMY; IN vivo studies; DESCRIPTIVE statistics; CHRONIC kidney failure; ATORVASTATIN; ETANERCEPT; NERVE tissue proteins; ANIMAL experimentation; VENTRICULAR arrhythmia; OXIDOREDUCTASES; WESTERN immunoblotting; ONE-way analysis of variance; CARDIAC arrest; STAINS &; staining (Microscopy); BLOOD pressure; COLLECTION &; preservation of biological specimens; DATA analysis software; ELECTROPHYSIOLOGY; TUMOR necrosis factors; INTERLEUKIN-1; DISEASE risk factors
- Publication
Journal of Geriatric Cardiology, 2024, Vol 21, Issue 4, p443
- ISSN
1671-5411
- Publication type
Article
- DOI
10.26599/1671-5411.2024.04.007