Influence of androgen on myocardial apoptosis and expression of myocardial IR and IRS‑1 in chronic heart failure rat models

Wang,Yu; Hu,Yang; Zeng,Zhaoping; Li,Yinghua; Su,Huipeng; Li,Yiwei; Wang,Ruiping; Zhang,Mingqian; Yang,Yongli; Deng,Jie

doi:10.3892/mmr.2017.8018

January-2018 Volume 17 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

January-2018 Volume 17 Issue 1

Full Size Image

Article

Influence of androgen on myocardial apoptosis and expression of myocardial IR and IRS‑1 in chronic heart failure rat models

Authors:
- Yu Wang
- Yang Hu
- Zhaoping Zeng
- Yinghua Li
- Huipeng Su
- Yiwei Li
- Ruiping Wang
- Mingqian Zhang
- Yongli Yang
- Jie Deng
View Affiliations / Copyright

Affiliations: Department of Geriatric Medicine, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650051, P.R. China, Department of Cardiology, The People’s Hospital of Qiandongnan of Guizhou Province, Qiandongnan, Guizhou 556000, P.R. China
Pages: 1057-1064
|
Published online on: November 8, 2017

https://doi.org/10.3892/mmr.2017.8018
Expand metrics +

Abstract

The present study aimed to investigate the effect of androgens on chronic heart failure (CHF) in a rat model. A total of 120 Sprague Dawley male rats were randomly divided into the following groups: (A) sham operation group, (B) castrated group, (C) heart failure (HF) group, (D) castrated + HF group, and (E) castrated + HF + testosterone (T) replacement therapy group. There were 20 rats in group A, and 25 rats in the other groups. Surgical castration was performed on groups B, D and E, and T replacement therapy was administered to group E. Groups C, D and E were treated with doxorubicin hydrochloride to prepare the CHF animal model. The insulin sensitivity index (ISI) was calculated from fasting blood glucose and fasting insulin levels. Echocardiography was performed. Venous blood was collected for plasma T level test. Myocardial tissue was used for apoptosis index analysis. The expression levels of myocardial insulin receptor (IR) and insulin receptor substrate‑1 (IRS‑1) were measured by reverse transcription semi‑quantitative polymerase chain reaction. Compared with group A, the T level and ISI decreased, whereas the expression level of IR and IRS‑1 were increased in the CHF group (P<0.05). Following castration, the T level and ISI were significantly decreased, and the expression of IR and IRS‑1 were increased compared with the uncastrated CHF rats (P<0.01). Following androgen administration, the ISI increased, expression of IR and IRS‑1 decreased, and the myocardial apoptosis index decreased (P<0.05). Taken together, these results demonstrated that androgen supplementation could improve insulin resistance and affect the expression of IR and IRS‑1 in CHF, thereby reducing myocardial apoptosis and improving cardiac function.

View Figures

View References

1	Erdei T, Smiseth OA, Marino P and Fraser AG: A systematic review of diastolic stress tests in heart failure with preserved ejection fraction, with proposals from the EU-FP7 MEDIA study group. Eur J Heart Fail. 16:1345–1361. 2014. View Article : Google Scholar : PubMed/NCBI
2	Tohmo H, Karanko M, Korpilahti K, Scheinin M, Viinamäki O and Neuvonen P: Enalaprilat in acute intractable heart failure after myocardial infarction: A prospective, consecutive sample, before-after trial. Crit Care Med. 22:965–973. 1994. View Article : Google Scholar : PubMed/NCBI
3	Pugh PJ, Jones RD, Jones TH and Channer KS: Heart failure as an inflammatory condition: Potential role for androgens as immune modulators. Eur J Heart Fail. 4:673–680. 2002. View Article : Google Scholar : PubMed/NCBI
4	van de Weijer T, Schrauwen-Hinderling VB and Schrauwen P: Lipotoxicity in type 2 diabetic cardiomyopathy. Cardiovasc Res. 92:10–18. 2011. View Article : Google Scholar : PubMed/NCBI
5	Papadimitriou L and Kalogeropoulos AP: Inflammatory biomarkers and therapeutic targets in heart failure. Curr Med Chem. 22:2716–2726. 2015. View Article : Google Scholar : PubMed/NCBI
6	Ashrafian H, Frenneaux MP and Opie LH: Metabolic mechanisms in heart failure. Circulation. 116:434–448. 2007. View Article : Google Scholar : PubMed/NCBI
7	Schroeder ET, Vallejo AF, Zheng L, Stewart Y, Flores C, Nakao S, Martinez C and Sattler FR: Six-week improvements in muscle mass and strength during androgen therapy in older men. J Gerontol A Biol Sci Med Sci. 60:1586–1592. 2005. View Article : Google Scholar : PubMed/NCBI
8	Huang CK, Lee SO, Chang E, Pang H and Chang C: Androgen receptor (AR) in cardiovascular diseases. J Endocrinol. 229:R1–R16. 2016. View Article : Google Scholar : PubMed/NCBI
9	De Smet MA, Lapauw B and De Backer T: Sex steroids in relation to cardiac structure and function in men. Andrologia. 49:2017.doi: 10.1111/and.12610. View Article : Google Scholar : PubMed/NCBI
10	Marsh JD, Lehmann MH, Ritchie RH, Gwathmey JK, Green GE and Schiebinger RJ: Androgen receptors mediate hypertrophy in cardiac myocytes. Circulation. 98:256–261. 1998. View Article : Google Scholar : PubMed/NCBI
11	Johansson A, Ahrén B, Forsberg H and Olsson T: Testosterone and diurnal rhythmicity of leptin, TNF-alpha and TNF-II receptor in insulin-resistant myotonic dystrophy patients. Int J Obes Relat Metab Disord. 26:1386–1392. 2002. View Article : Google Scholar : PubMed/NCBI
12	Boyanov MA, Boneva Z and Christov VG: Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male. 6:1–7. 2003. View Article : Google Scholar : PubMed/NCBI
13	Borissova AM, Tankova T, Kamenova P, Dakovska L, Kovacheva R, Kirilov G, Genov N, Milcheva B and Koev D: Effect of hormone replacement therapy on insulin secretion and insulin sensitivity in postmenopausal diabetic women. Gynecol Endocrinol. 16:67–74. 2002. View Article : Google Scholar : PubMed/NCBI
14	de Simone G, Devereux RB and Wallerson DC: Echocardiographic assessment of left ventricular hypertrophy in rats using a simplified approach. Am J Hypertens. 7:555–558. 1994. View Article : Google Scholar : PubMed/NCBI
15	Doehner W, von Haehling S and Anker SD: Insulin resistance in chronic heart failure. J Am Coll Cardiol. 52:239–240. 2008. View Article : Google Scholar : PubMed/NCBI
16	Kontoleon PE, Anastasiou-Nana MI, Papapetrou PD, Alexopoulos G, Ktenas V, Rapti AC, Tsagalou EP and Nanas JN: Hormonal profile in patients with congestive heart failure. Int J Cardiol. 87:179–183. 2003. View Article : Google Scholar : PubMed/NCBI
17	Zhou Q, Liu JH, Ke J, CheN B and MA YX: Effects of testosterone on left ventricular function of male rats with chronic heart failure. China J Modern Med. 15:2104–2106. 2005.
18	Paolisso G, De Riu S, Marrazzo G, Verza M, Varricchio M and D'Onofrio F: Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure. Metabolism. 40:972–977. 1991. View Article : Google Scholar : PubMed/NCBI
19	Wong AK, AlZadjali MA, Choy AM and Lang CC: Insulin resistance: A potential new target for therapy in patients with heart failure. Cardiovasc Ther. 26:203–213. 2008. View Article : Google Scholar : PubMed/NCBI
20	Witteles RM and Fowler MB: Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options. J Am Coll Cardiol. 51:93–102. 2008. View Article : Google Scholar : PubMed/NCBI
21	Gao F, Gao E, Yue TL, Ohlstein EH, Lopez BL, Christopher TA and Ma XL: Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: The roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation. Circulation. 105:1497–1502. 2002. View Article : Google Scholar : PubMed/NCBI
22	Bonagura TW, Zhou H, Babischkin JS, Pepe GJ and Albrecht ED: Expression of P-450 aromatase, estrogen receptor α and β, and α-inhibin in the fetal baboon testis after estrogen suppression during the second half of gestation. Endocrine. 39:75–82. 2011. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Influence of androgen on myocardial apoptosis and expression of myocardial IR and IRS‑1 in chronic heart failure rat models

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Related Articles