Research Article Open Access

Reduced Levels of Testosterone Induce LDL Oxidation and Atherosclerotic Lesions Involving Inflammatory Imbalance and Reduced Macrophage Apoptosis

Placielle Fiorezi Filete1, Flávia de Souza Andrade Moraes1, Girlandia Alexandre Brasil1, Ewelyne Miranda de Lima1, Bianca Prandi Campagnaro1, Dominik Lenz1, Denise Coutinho Endringer1, Dulcineia Saes Parra Abdalla2, Nazaré Souza Bissoli3, Thiago de Melo Costa Pereira1 and Tadeu Uggere de Andrade1
  • 1 Pharmaceutical Sciences Graduate Program, University Vila Velha, Vila Velha, ES, Brazil
  • 2 School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
  • 3 Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitória, ES, Brazil

Abstract

Atherosclerosis is among the major cardiovascular diseases that cause death in the world. Men who are deficient in androgen hormones are more susceptible to this disease. The aim of this study was to evaluate the influence of reduced levels of testosterone on the lipid profile, pro and anti-inflammatory cytokines, apoptosis of peritoneal macrophages and the development of atherosclerosis in LDLr-/-mice, as well as on the levels of OxLDL in healthy male humans. Tissues and organs of the experimental animals were used to evaluate lipid deposition in aorta and apoptosis of peritoneal macrophages. In humans the levels of testosterone and OxLDL were analyzed in blood samples from healthy male subjects, who were divided into two groups: low level and high level of testosterone. Animals with decreased testosterone did not present changes in the lipid profile or the levels of IL-6 and TNF-α. However, a decrease in IL-10 and an increase in the IL-6/IL-10 and TNF-α/IL-10 ratios were observed. An increase in the aorta lipid deposition was observed and a decrease in macrophage apoptosis was also demonstrated. In humans, there was an increase of OxLDL in the group with lower levels of testosterone. The findings suggest that decreasing endogenous testosterone levels may induce the development of atherosclerosis, with participation of inflammatory response and macrophage apoptosis. This is reinforced by our human studies, where individuals with low testosterone levels had higher LDL oxidation, which may predict a high atherosclerotic risk for these men.

OnLine Journal of Biological Sciences
Volume 19 No. 4, 2019, 260-271

DOI: https://doi.org/10.3844/ojbsci.2019.260.271

Submitted On: 4 September 2019 Published On: 6 December 2019

How to Cite: Filete, P. F., Andrade Moraes, F. S., Brasil, G. A., de Lima, E. M., Campagnaro, B. P., Lenz, D., Endringer, D. C., Abdalla, D. S. P., Bissoli, N. S., Pereira, T. M. C. & de Andrade, T. U. (2019). Reduced Levels of Testosterone Induce LDL Oxidation and Atherosclerotic Lesions Involving Inflammatory Imbalance and Reduced Macrophage Apoptosis. OnLine Journal of Biological Sciences, 19(4), 260-271. https://doi.org/10.3844/ojbsci.2019.260.271

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Keywords

  • Androgens
  • Atherosclerosis
  • Apoptosis
  • Oxidized LDL