Abstract

BackgroundMyocardial fibrosis is a critical pathological basis for the poor prognosis of cardiovascular diseases. Studies have found that myocardial fibrosis is closely associated with exposure to environmental estrogens such as nonylphenol (NP), as a representative of environmental estrogens. The aim of this study was to examine the effects of NP chronic exposure on myocardial fibrosis as well as cardiac structure and function. Forty Sprague–Dawley rats were randomly divided into four groups (n = 10): control group (C), low NP dose (0.4 mg/kg, L), medium NP dose (4 mg/kg, M), and high NP dose (40 mg/kg, H) groups. The NP dose groups were gavaged with NP for 180 days.ResultsThe NP level in the heart of the NP groups was significantly higher than those in the control group (F = 43.658, P < 0.001). Serum aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isozyme (CK-MB), lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) significantly increased in the NP groups compared with the control group (P < 0.05). Histopathological examination of the heart biopsy illustrates that in the medium and high NP groups, the fibrous connective tissue had a disordered and loose gridding shape, muscle fibers had fractured, and muscle fibers were loose with a widened gap. Extensive inflammatory cell infiltration and fibroblast proliferation in the myocardial interstitium were also found. With increasing NP dose, the degree of muscle fiber loosing and disorder became more significant in the NP-treatment groups, and the collagen volume fraction (CVF) was higher than that in the control group (P < 0.01). Compared with the control group, the expression of collagen I and collagen III increased significantly in the medium and high NP groups (P < 0.05). The values of the systolic thickness of the left ventricular anterior wall (LVAWs), the diastolic thickness of the left ventricular posterior wall (LVPWd), the systolic thickness of the left ventricular posterior wall (LVPWs), and the left ventricular anterior wall (LVAWd) in the NP groups are were slightly lower than those in of the control group. The values of left ventricular end systolic dimensions (LVIDs) in the NP groups increased compared with the control group.ConclusionsLong-term NP exposure could lead to fibrosis in the rat myocardium, which is characterized by increased expressions of myocardial collagen I and collagen III, as well as elevated cardiac enzymes. In addition, the cardiac structure was affected and changes were observed in the thinner ventricular wall and as an enlarged ventricular cavity.

Highlights

  • Myocardial fibrosis is a critical pathological basis for the poor prognosis of cardiovascular diseases

  • Effects of NP exposure on serum myocardial enzymes Serum Aspartate aminotransferase (AST) (F = 43.388, P = 0.0001), creatine kinase (CK) (F = 33.456, P = 0.0001), Creatine kinase isozyme (CK-MB) (F = 13.929, P = 0.0001), lactate dehydrogenase (LDH) (F = 78.456, P = 0.0001), and a-HBDH (F = 26.237, P = 0.0001) significantly increased in the NP groups compared with the control group

  • This study showed that NP is accumulated in the cardiac tissue, leading to myocardial fibrosis, which mainly manifests as increased expression of collagen I and collagen III in the myocardium

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Summary

Introduction

Myocardial fibrosis is a critical pathological basis for the poor prognosis of cardiovascular diseases. Studies have found that myocardial fibrosis is closely associated with exposure to environmental estrogens such as nonylphenol (NP), as a representative of environmental estrogens. Myocardial fibrosis is a critical pathological basis and an important influencing factor for the poor prognosis of cardiovascular diseases, such as chronic heart failure [2,3,4]. Studies have found that myocardial fibrosis is closely associated with exposure to environmental endocrine disruptors (EEDs). Bisphenol A (BPA) up-regulated collagen I and collagen III expressions in cardiac fibroblasts of male rats by activating the ERK1/2 pathway, which resulted in myocardial fibrosis, similar to the mechanism of 17β-estradiol increasing collagen in cardiac fibroblasts [5, 6]. It has been proved that EEDs have estrogenic activity similar to the in vivo estrogens, which simulate physiological and biochemical effects of endogenous estrogen and interfere with the normal endocrine system after entering the body [12]

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