Preview

Russian Journal of Cardiology

Advanced search

LEPR isoform expression changes in local fat depots in coronary atherosclerosis and acquired heart defects

https://doi.org/10.15829/1560-4071-2024-5826

EDN: RUVAOW

Abstract

Aim. To evaluate the expression of leptin receptor isoforms in local fat depots in patients with coronary artery disease (CAD) and acquired heart defects (AHDs).

Material and methods. The study included 120 patients with CAD. The comparison group consisted of 96 patients with degenerative aortic stenosis (AS). Expression of six leptin receptor isoforms (LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, LEPR4) was assessed using quantitative real-time polymerase chain reaction in subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) adipose tissue. Statistical processing was carried out using the Statistica 10.0 and SPSS 17.0 for Windows software package.

Results. In EAT, minimal expression of LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, LEPR4 was detected relative to SAT and PVAT in the group of CAD patients. In patients with CAD, mRNA levels of six LEPR isoforms were lower than in patients with AS. In indi­viduals with AHDs, a decrease in the expression of LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, LEPR4 in SAT relative to EAT and PVAT was recorded. However, only the LEPR1 and LEPR2 isoforms were significantly lower in SAT in patients with AS when com­pared with patients with CAD. In PVAT, the maximum mRNA levels of six LEPR isoforms were found in both groups. There were no significant differences in LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, LEPR4 expression between patients with CAD and AHDs.

Conclusion. Patients with CAD are characterized by a marked decrease in the expression of six LEPR isoforms in EAT. A decrease in the expression of studied LEPR isoforms in EAT is associated with impaired adipogenesis, adipocyte hypertrophy, insulin resistance, increased proinflammatory factors, hyperleptinemia, and progression of atherosclerosis. The identified features of EAT in patients with СФВ can probably have both local and systemic negative effects on the cardiovascular system.

About the Authors

E. E. Gorbatovskaya
Research Institute for Complex Issues of Cardiovascular Diseases; Kemerovo State Medical University
Russian Federation

Evgeniya E. Gorbatovskaya - Post-graduate Student, Research Laboratory Assistant, Laboratory for Homeostasis Research, Research Institute of Complex Problems of Cardiovascular Diseases; Assistant at the Department of Medical Biochemistry, Kemerovo State Medical University.

Kemerovo


Competing Interests:

None



E. V. Belik
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Ekaterina V. Belik - MD, PhD, Researcher, Laboratory for Homeostasis Research.

Kemerovo


Competing Interests:

None



Yu. A. Dyleva
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Yulia A. Dyleva - MD, PhD, Senior Researcher, Laboratory for Homeostasis Research.

Kemerovo


Competing Interests:

None



E. G. Uchasova
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Evgeniya G. Uchasova - MD, PhD, Senior Researcher, Laboratory for Homeostasis Research.

Kemerovo


Competing Interests:

None



A. V. Ponasenko
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Anastasia V. Ponasenko - MD, PhD, Head Laboratory of Genomic Medicine, Department of Experimental Medicine.

Kemerovo


Competing Interests:

None



E. V. Fanaskova
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Elena V. Fanaskova - MD, PhD, Head transfusion room.

Kemerovo


Competing Interests:

None



A. N. Stasev
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Alexander N. Stasev - MD, PhD, Researcher, Laboratory of Heart Diseases, Department of Cardiac and Vascular Surgery.

Kemerovo


Competing Interests:

None



O. V. Gruzdeva
Research Institute for Complex Issues of Cardiovascular Diseases; Kemerovo State Medical University
Russian Federation

Olga V. Gruzdeva - MD, DSc, Professor of the Russian Academy of Sciences, Head of the Laboratory for Homeostasis Research, Research Institute of Complex Problems of Cardiovascular Diseases; Head of the Department of Medical Biochemistry, Kemerovo State Medical University.

Kemerovo


Competing Interests:

None



References

1. Abdul-Rahman T, Lizano-Jubert I, Garg N, et al. The common pathobiology between coronary artery disease and calcific aortic stenosis: Evidence and clinical implications. Prog Cardiovasc Dis. 2023;79:89-99. doi:10.1016/j.pcad.2023.06.002.

2. Raman P, Khanal S. Leptin in Atherosclerosis: Focus on Macrophages, Endothelial and Smooth Muscle Cells. Int J Mol Sci. 2021;22(11):5446. doi:10.3390/ijms22115446.

3. Liu Y, Gu Y, Shen Y, et al. Association Between Serum Leptin Level and Calcific Aortic Valve Disease. J Am Heart Assoc. 2019;(19):e012495. doi:10.1161/JAHA.119.012495.

4. Liu Z, Xiao T, Liu H. Leptin signaling and its central role in energy homeostasis. Front Neurosci. 2023;17:1238528. doi:10.3389/fnins.2023.1238528.

5. Picó C, Palou M, Pomar CA, et al. Leptin as a key regulator of the adipose organ. Rev Endocr Metab Disord. 2022;23(1):13-30. doi:10.1007/s11154-021-09687-5.

6. Martínez-Sánchez N. There and Back Again: Leptin Actions in White Adipose Tissue. Int J Mol Sci. 2020;21(17):6039. doi:10.3390/ijms21176039.

7. Hu H, Garcia-Barrio M, Jiang ZS, et al. Roles of Perivascular Adipose Tissue in Hyper­tension and Atherosclerosis. Antioxid Redox Signal. 2021;34(9):736-49. doi:10.1089/ars.2020.8103.

8. Sinitsky MY, Ponasenko AV, Gruzdeva OV. Genetic profile and secretome of adipocytes from visceral and subcutaneous adipose tissue in patients with cardiovascular diseases. Complex Issues of Cardiovascular Diseases. 2017;6(3):155-65. (In Russ.) doi:10.17802/2306-1278-2017-6-3-155-165.

9. Wauman J, Zabeau L, Tavernier J. The Leptin Receptor Complex: Heavier Than Expec­ted? Front Endocrinol (Lausanne). 2017;8:30. doi:10.3389/fendo.2017.00030.

10. Tsirigotaki A, Dansercoer A, Verschueren KHG, et al. Mechanism of receptor assembly via the pleiotropic adipokine Leptin. Nat Struct Mol Biol. 2023;30(4):551-63. doi:10.1038/s41594-023-00941-9.

11. Chumakova GA, Ott AV, Veselovskaya NG, et al. Pathogenetic mechanisms of leptin resistance. Russian Journal of Cardiology. 2015;(4):107-10. (In Russ.) doi:10.15829/1560-4071-2015-4-107-110.

12. Bornstein SR, Abu-Asab M, Glasow A, et al. Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture. Diabetes. 2000;49(4):532-8. doi:10.2337/diabetes.49.4.532.

13. Ambele MA, Dhanraj P, Giles R, et al. Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways. Int J Mol Sci. 2020;21(12):4283. doi:10.3390/ijms21124283.

14. Iacobellis G. Epicardial adipose tissue in contemporary cardiology. Nat Rev Cardiol. 2022;19(9):593-606. doi:10.1038/s41569-022-00679-9.

15. Packer M. Epicardial Adipose Tissue May Mediate Deleterious Effects of Obesity and Inflammation on the Myocardium. J Am Coll Cardiol. 2018;71(20):2360-72. doi:10.1016/j.jacc.2018.03.509.

16. Manna P, Jain SK. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Asso­ciated Health Risks: Causes and Therapeutic Strategies. Metab Syndr Relat Disord. 2015;13(10):423-44. doi:10.1089/met.2015.0095.

17. Becerril S, Rodríguez A, Catalán V, et al. Functional Relationship between Leptin and Nitric Oxide in Metabolism. Nutrients. 2019;11(9):2129. doi:10.3390/nu11092129.

18. Kim JI, Huh JY, Sohn JH, et al. Lipid-overloaded enlarged adipocytes provoke insulin resistance independent of inflammation. Mol Cell Biol. 2015;35(10):1686-99. doi:10.1128/MCB.01321-14.

19. Huan JN, Li J, Han Y, et al. Adipocyte-selective reduction of the leptin receptors induced by antisense RNA leads to increased adiposity, dyslipidemia, and insulin resistance. J Biol Chem. 2003;278(46):45638-50. doi:10.1074/jbc.M304165200.

20. Hall ME, Harmancey R, Stec DE. Lean heart: Role of leptin in cardiac hypertrophy and metabolism. World J Cardiol. 2015;7(9):511-24. doi:10.4330/wjc.v7.i9.511.


Supplementary files

  • Special aspects of LEPRisoform expression in cardiac local fat depots in patients with coronary and non-coronary pathologies were revealed.
  • Patients with coronary artery disease show a marked reduction in the expression of six LEPRisoforms in epicardial adipose tissue (EAT).
  • Changes in LEPRexpression in EAT in patients with coronary pathology are associated with impaired adipogenesis, adipocyte hypertrophy, insulin resistance, increased proinflammatory factors, hyperleptinemia, and progression of atherosclerosis.

Review

For citations:


Gorbatovskaya E.E., Belik E.V., Dyleva Yu.A., Uchasova E.G., Ponasenko A.V., Fanaskova E.V., Stasev A.N., Gruzdeva O.V. LEPR isoform expression changes in local fat depots in coronary atherosclerosis and acquired heart defects. Russian Journal of Cardiology. 2024;29(8):5826. (In Russ.) https://doi.org/10.15829/1560-4071-2024-5826. EDN: RUVAOW

Views: 146


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1560-4071 (Print)
ISSN 2618-7620 (Online)