Elsevier

Neuropeptides

Volume 78, December 2019, 101975
Neuropeptides

The influence of post-infarct heart failure and high fat diet on the expression of apelin APJ and vasopressin V1a and V1b receptors

https://doi.org/10.1016/j.npep.2019.101975Get rights and content

Highlights

  • Post-infarct heart failure causes changes in the expression of APJR, V1aR and V1bR.

  • Expression of APJR, V1aR and V1bR are regulated by a high fat diet (HFD).

  • Combination of post-infarct heart failure and a HFD have a different effect.

Abstract

Vasopressin and apelin are reciprocally regulated hormones which are implicated in the pathophysiology of heart failure and the regulation of metabolism; however, little is known about their interactions under pathological conditions. In this study, we determined how post-infarct heart failure (HF) and a high fat diet (HFD) affect expression of the apelin APJ receptor (APJR) and the V1a (V1aR) and V1b (V1bR) vasopressin receptors in the hypothalamus, the heart, and the retroperitoneal adipose tissue. We performed experiments in male 4-week-old Sprague Dawley rats. The animals received either a normal fat diet (NFD) or a HFD for 8 weeks, then they underwent left coronary artery ligation to induce HF or sham surgery (SO), followed by 4 weeks of NFD or HFD. The HF rats showed higher plasma concentration of NT-proBNP and copeptin. The HF reduced the APJR mRNA expression in the hypothalamus. The APJR and V1aR protein levels in the hypothalamus were regulated both by HF and HFD, while the V1bR protein level in the hypothalamus was mainly influenced by HF. APJR mRNA expression in the heart was significantly higher in rats on HFD, and HFD affected the reduction of the APJR protein level in the right ventricle. The regulation of APJR, V1aR and V1bR expression in the heart and the retroperitoneal adipose tissue were affected by both HF and HFD. Our study demonstrates that HF and HFD cause significant changes in the expression of APJR, V1aR and V1bR, which may have an important influence on the cardiovascular system and metabolism.

Introduction

Heart failure is still an important clinical problem. It is estimated that heart failure develops in about 1%–2% of people under 70 years old in highly developed countries. However, in people over 70 years old, the incidence of heart failure is estimated to be as much as 10% (Ponikowski et al., 2016). The main factor for the development of heart failure is myocardial infarction (Ponikowski et al., 2016). A key role in the pathogenesis of many cardiovascular diseases is played by obesity (Morris et al., 2015). A characteristic feature of obesity is the excessive accumulation of adipose tissue in the body (Frühbeck et al., 2013). Recently, adipose tissue has been also recognized as a neuroendocrine organ synthesizing and releasing into circulation many biologically active substances called adipokines, among which apelin seems to be particularly involved in regulation of cardiovascular system and metabolism (Molica et al., 2015).

Apelin and its receptor APJ (APJR) play an important role in the pathogenesis of many cardiovascular diseases, including heart failure (Kuba et al., 2019), although both central and peripheral mechanisms have not yet been fully elucidated. The direct role of apelin/APJR in the pathogenesis of heart failure appears to be confirmed by experimental and clinical studies (Sheikh et al., 2008; Folino et al., 2015). In addition, apelin is increasingly seen as a potential therapeutic agent in patients with heart failure (Seifirad and Masoudkabir, 2013; Ureche et al., 2019). Additionally, it was shown that apelin/APJR can play an important role in the central regulation of metabolism (Valle et al., 2008; Clarke et al., 2009; Reaux-Le Goazigo et al., 2011). Besides its central actions, apelin has been shown to exert systemic effects on glucose and lipid metabolism as well as regulation of insulin secretion via its APJR (Bertrand et al., 2015). It appears that a high fat diet can also change the activity and expression of apelin and APJR (Valle et al., 2008; Cudnoch-Jedrzejewska et al., 2015). The protein and mRNA of preproapelin have been detected in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus, which are also the main place for the synthesis of vasopressin (AVP) (De Mota et al., 2004; Yang et al., 2007). Furthermore, apelin is involved in the downregulation of the activity of vasopressinergic neurons (De Mota et al., 2004).

Vasopressin exerts its effects on the body via the V1 (V1a vasopressin receptor, V1aR and V1b vasopressin receptor, V1bR), and V2 receptor. V2 receptors (V2Rs) have been detected mainly in the kidneys. In contrast, the V1aRs are located in many structures of the central nervous system (CNS) as well as in peripheral organs such as the heart, vessels and adipose tissues (Szczepanska-Sadowska et al., 2018; Tran et al., 2016). V1bRs have been found mainly in the pituitary gland where it takes part in the stress response by regulating adrenocorticotropic hormone (ACTH) secretion (Szczepanska-Sadowska et al., 2018). It has been demonstrated that changes in the activity of the cerebral vasopressinergic system, principally AVP and V1aR, occur in the course of heart failure (Szczepanska-Sadowska et al., 2018; Reis et al., 2016). It has been shown that AVP by V1aR can play an important role in reducing body weight and in the regulation of metabolism (Aoyagi et al., 2009).

Based on the available studies, it can be assumed that the apelinergic and the vasopressinergic systems play a significant role in the pathogenesis of heart failure and in the regulation of metabolism. In addition, post-infarct heart failure (HF) and a high fat diet (HFD) have a significant impact on the activity of both the apelinergic and the vasopressinergic systems. Therefore, the aim of this study was to determine whether HF and HFD, applied separately or in combination, are associated with changes in the mRNA and protein expression of APJR, V1aR and V1bR in the brain, the heart and the adipose tissue of Sprague Dawley rats.

Section snippets

Materials and methods

Experiments were performed on 27 male 4-week-old Sprague Dawley rats, divided into the following groups: sham-operated rats on a normal fat diet (SO NFD; n = 7), sham-operated rats on a high fat diet (SO HFD; n = 6), post-infarct heart failure rats on a normal fat diet (HF NFD; n = 7), and post-infarct heart failure rats on a high fat diet (HF HFD, n = 7).

Our research was approved by the Second Local Animal Research Ethics Committee of the Medical University of Warsaw.

The rats were housed in

Characteristics of the animals

One-way ANOVA revealed significant differences in the body weight between the examined groups of rats [F(3.23) = 3.215, p < 0.05], whereas individual comparisons by post hoc Tukey test showed a lack of significant differences in body weight (Table 1).

Significant differences were found between the infarction surface of the groups (p < 0.001; Kruskal-Wallis test). The infarction surface was significantly higher in the HF HFD rats in comparison with the HF NFD rats (p < 0.001) (Table 1).

One-way

Discussion

The main finding of our study is that post-infarct heart failure and a high fat diet differentially affect the expression of mRNA and protein levels of the APJR and the V1aR and V1bR in the hypothalamus, in the left and the right ventricles and in the retroperitoneal adipose tissue. The observed differences between mRNA expression and the translation efficiency suggest transcription-independent regulation of translation due to the epigenetic imprinting of mRNA (Slobodin et al., 2017) or other

Conclusion

Our study showed that post-infarct heart failure and a high fat diet cause significant changes in mRNA expression and protein levels of APJR, V1aR and V1bR in the hypothalamus, in the left and the right ventricles and in the retroperitoneal adipose tissue. Additionally, we have demonstrated that the combination of HF and HFD caused a different effect than either factor separately. The observed changes in the expression of the examined receptors may have important implications for the regulation

Acknowledgements

The authors are thankful to Mrs. Malgorzata Kowalczyk for her competent technical assistance and to Mr. Marcin Kumosa for the preparation of the figures.

Funding

This work was supported by the Grant Preludium 9 from the National Science Centre (2013/09/N/NZ4/01730) and by the Grant Preludium 11 from the National Science Centre (2016/21/N/NZ4/03758).

Declaration of Competing Interests

None declared.

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