SFRP5 as a new cardiovascular biological marker: a literature review

Cover Page

Cite item

Full Text

Abstract

Research into new biological markers may help early diagnosis and effective therapy for cardiology patients. The use of biomarkers to evaluate patients has made a major impact in oncology, but is still in its infancy in the cardiology field. Studies on secreted frizzled-related protein 5 (SFRP5) have revealed its potential use as a marker of cardiovascular pathology. Preclinical studies have highlighted the important role this protein plays in many biological processes. It reduces the proliferation and migration of cardiac fibroblasts and suppresses the Wnt5A/JNK signaling pathway thus reducing the severity of oxidative stress and inflammation. It normalizes nitric oxide production and has several other effects. However, recent clinical studies of SFRP5 have produced conflicting data. Nevertheless, this protein shows promise as a marker for several metabolic and cardiovascular diseases. Preliminary data also suggest SFRP5 may be a therapeutic target. Further study of SFRP5 and its role in cardiovascular pathology is necessary, and will create new diagnostic and prognostic possibilities for this biological marker.

About the authors

Amina M. Alieva

Pirogov Russian National Research Medical University

Author for correspondence.
Email: amisha_alieva@mail.ru
ORCID iD: 0000-0001-5416-8579
SPIN-code: 2749-6427

MD, Cand. Sci. (Med.)

Russian Federation, 1 Ostrovityanova Str., 117997, Moscow

Natalia V. Teplova

Pirogov Russian National Research Medical University

Email: teplova.nv@yandex.ru
ORCID iD: 0000-0002-7181-4680
SPIN-code: 9056-1948

MD, D. Sci. (Med.)

Russian Federation, 1 Ostrovityanova Str., 117997, Moscow

Irina E. Baykova

Pirogov Russian National Research Medical University

Email: 1498553@mail.ru
ORCID iD: 0000-0003-0886-6290
SPIN-code: 3054-8884

MD, Cand. Sci. (Med.)

Russian Federation, 1 Ostrovityanova Str., 117997, Moscow

Kira V. Voronkova

Pirogov Russian National Research Medical University

Email: kiravoronkova@yandex.ru
ORCID iD: 0000-0003-1111-6378
SPIN-code: 1636-7627

MD, D. Sci. (Med.)

Russian Federation, 1 Ostrovityanova Str., 117997, Moscow

Lidiya M. Shnakhova

Sechenov First Moscow State Medical University (Sechenov Unuiversity)

Email: shnakhova_l_m@staff.sechenov.ru
ORCID iD: 0000-0003-3000-0987
SPIN-code: 5549-5823

doctor consultant

Russian Federation, Moscow

Lyudmila M. Makeeva

Pirogov Russian National Research Medical University

Email: mila-mm@yandex.ru
ORCID iD: 0000-0003-0755-4869

Department Assist.

Russian Federation, 1 Ostrovityanova Str., 117997, Moscow

Irina A. Kotikova

Pirogov Russian National Research Medical University

Email: kotikova.ia@mail.ru
ORCID iD: 0000-0001-5352-8499
SPIN-code: 1423-7300

6th year student

Russian Federation, 1 Ostrovityanova Str., 117997, Moscow

Igor G. Nikitin

Pirogov Russian National Research Medical University

Email: igor.nikitin.64@mail.ru
ORCID iD: 0000-0003-1699-0881
SPIN-code: 3595-1990

MD, D. Sci. (Med.), Prof.

Russian Federation, 1 Ostrovityanova Str., 117997, Moscow

References

  1. Perk J. The 2016 version of the European Guidelines on Cardiovascular Prevention. Eur Heart J Cardiovasc Pharmacother. 2017;3(1):9–10.doi: 10.1093/ehjcvp/pvw030
  2. Kozhevnikova MV, Belenkov YuN. Biomarkers in Heart Failure: Current and Future. Kardiologiia. 2021;61(5):4–16. (In Russ).doi: 10.18087/cardio.2021.5. n1530
  3. Aliyeva AM, Reznik EV, Hasanova ET, et al. Clinical value of blood biomarkers in patients with chronic heart failure. The Russian Archives of Internal Medicine. 2018;8(5):333–345. (In Russ). doi: 10.20514/2226-6704-2018-8-5-333-345
  4. Aliyevа AM, Almazova II, Pinchuk TV, et al. The value of copeptin in the diagnosis and prognosis of cardiovascular diseases. Clinical Medicine (Russian Journal). 2020;98(3):203–209. (In Russ).doi: 10.30629/0023-2149-2020-98-3-203-209
  5. Alieva AM, Pinchuk TV, Voronkova KV, et al. Neopterin is a biomarker of chronic heart failure (review of modern literature). Consilium Medicum. 2021;23(10):756–759. (In Russ). doi: 10.26442/20751753.2021.10.201113
  6. Chu D, Nguyen T. Frizzled receptors and SFRP5 in lipid metabolism: Current findings and potential applications. Prog Mol Biol Transl Sci. 2023; 194:377–393. doi: 10.1016/bs.pmbts.2022.06.025
  7. Yadav S, Hussain S, Dwivedi P, et al. Assessment of serum Sfrp5/Wnt-5a level and its utility in the risk stratification of treatment naive patients with metabolic syndrome. J Immunoassay Immunochem. 2023;44(1):1–12.doi: 10.1080/15321819.2022.2104125
  8. Ren Y, Zhao H, Yin C, et al. Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation. Front Endocrinol (Lausanne). 2022; 13:873699. doi: 10.3389/fendo.2022.873699
  9. Jung H, Jung C. The Role of Anti-Inflammatory Adipokines in Cardiometabolic Disorders: Moving beyond Adiponectin. Int J Mol Sci. 2021;22(24):13529. doi: 10.3390/ijms222413529
  10. Mori H, Prestwich T, Reid M, et al. Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition. J Clin Invest. 2012;122(7):2405–2416. doi: 10.1172/JCI63604
  11. Ouchi N, Higuchi A, Ohashi K, et al. Sfrp5 Is an Anti-Inflammatory Adipokine That Modulates Metabolic Dysfunction in Obesity. Science. 2010;329(5990):454–457. doi: 10.1126/science.1188280
  12. Carstensen-Kirberg M, Rohrig K, Niersmann C, et al. Sfrp5 increases glucose-stimulated insulin secretion in the rat pancreatic beta cell line INS-1E. PLoS One. 2019;14(3): e0213650. doi: 10.1371/journal.pone.0213650
  13. Li Y, Tian M, Yang M, et al. Central Sfrp5 regulates hepatic glucose flux and VLDL-triglyceride secretion. Metabolism. 2020; 103:154029.doi: 10.1016/j.metabol.2019.154029
  14. Wang X, Peng Q, Jiang F, et al. Secreted frizzled-related protein 5 protects against oxidative stress-induced apoptosis in human aortic endothelial cells via downregulation of Bax. J Biochem Mol Toxicol. 2017;31(12): e21978. doi: 10.1002/jbt.21978
  15. Liu W, Ji Y, Chu H, et al. SFRP5 mediates downregulation of the wnt5a/caveolin-1/JNK signaling pathway. J Endocrinol. 2020;247(3):263–272.doi: 10.1530/JOE-20-0328
  16. Teliewubai J, Ji H, Lu Y, et al. SFRP5 serves a beneficial role in arterial aging by inhibiting the proliferation, migration and inflammation of smooth muscle cells. Mol Med Rep. 2018;18(5):4682–4690. doi: 10.3892/mmr.2018.9467
  17. Nakamura K, Sano S, Fuster J, et al. Secreted Frizzled-related Protein 5 Diminishes Cardiac Inflammation and Protects the Heart from Ischemia/Reperfusion Injury. J Biol Chem. 2016;291(6):2566–2575. doi: 10.1074/jbc.M115.693937
  18. Bie Z-D, Sun L-Y, Geng C-L, et al. MiR-125b regulates SFRP5 expression to promote growth and activation of cardiac fibroblasts. Cell Biol Int. 2016;40(11):1224–1234. doi: 10.1002/cbin.10677
  19. Ding N, Zheng C. Secreted frizzled-related protein 5 promotes angiogenesis of human umbilical vein endothelial cells and alleviates myocardial injury in diabetic mice with myocardial infarction by inhibiting Wnt5a/JNK signaling. Bioengineered. 2022;13(5):11656–11667. doi: 10.1080/21655979.2022.2070964
  20. Hong P, Wang L, Wang H, et al. Effect of Secreted Frizzled-Related Protein 5 in Mice with Heart Failure. Evid Based Complement Alternat Med. 2022; 2022:1606212. doi: 10.1155/2022/1606212
  21. Huang X, Yan Y, Zheng W, et al. Secreted Frizzled-Related Protein 5 Protects Against Cardiac Rupture and Improves Cardiac Function Through Inhibiting Mitochondrial Dysfunction. Front Cardiovasc Med. 2021; 8:682409. doi: 10.3389/fcvm.2021.682409
  22. Sun M, Wang W, Min L, et al. Secreted frizzled-related protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway. J Orthop Surg Res. 2021;16(1):129.doi: 10.1186/s13018-021-02260-5
  23. Cho Y, Kang Y, Lee S, et al. Effect of SFRP5 (Secreted Frizzled-Related Protein 5) on the WNT5A (Wingless-Type Family Member 5A)-Induced Endothelial Dysfunction and Its Relevance with Arterial Stiffness in Human Subjects. Arterioscler Thromb Vasc Biol. 2018;38(6):1358–1367. doi: 10.1161/ATVBAHA.117.310649
  24. Akoumianakis I, Sanna F, Margaritis M, et al. Adipose tissue-derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases. Sci Transl Med. 2019;11(510): eaav5055. doi: 10.1126/scitranslmed. aav5055
  25. Carstensen-Kirberg M, Kannenberg JM, Huth C, et al. Inverse associations between serum levels of secreted frizzled-related protein-5 (SFRP5) and multiple cardiometabolic risk factors: KORA F4 study. Cardiovasc Diabetol. 2017;16(1):109. doi: 10.1186/s12933-017-0591-x
  26. Bai Y, Du Q, Jiang R, et al. Secreted Frizzled-Related Protein 5 is Associated with Glucose and Lipid Metabolism Related Metabolic Syndrome Components Among Adolescents in Northeastern China. Diabetes Metab Syndr Obes. 2021; 14:2735–2742. doi: 10.2147/DMSO.S301090
  27. Almario RU, Karakas SE. Roles of Circulating WNT-Signaling Proteins and WNT-Inhibitors in Human Adiposity, Insulin Resistance, Insulin Secretion, and Inflammation. Horm Metab Res. 2015;47(2):152–157.doi: 10.1055/s-0034-1384521
  28. Xu Q, Wang H, Li Y, et al. Plasma Sfrp5 levels correlate with determinants of the metabolic syndrome in Chinese adults. Diabetes Metab Res Rev. 2017;33(6): e2896. doi: 10.1002/dmrr.2896
  29. Lu Y-C, Wang C-P, Hsu C-C, et al. Circulating secreted frizzled-related protein 5 (Sfrp5) and wingless-type MMTV integration site family member 5a (Wnt5a) levels in patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2013;29(7):551–556. doi: 10.1002/dmrr.2426
  30. Wang B, Pan Y, Yang G, et al. Sfrp5/Wnt5a and leptin/adiponectin levels in the serum and the periarterial adipose tissue of patients with peripheral arterial occlusive disease. Clin Biochem. 2021;87:46–51.doi: 10.1016/j.clinbiochem.2020.11.002
  31. Oh YJ, Kim H, Kim AJ, et al. Reduction of Secreted Frizzled-Related Protein 5 Drives Vascular Calcification through Wnt3a-Mediated Rho/ROCK/JNK Signaling in Chronic Kidney Disease. Int J Mol Sci. 2020;21(10):3539.doi: 10.3390/ijms21103539
  32. Teliewubai J, Bai B, Zhou Y, et al. Association of asymptomatic target organ damage with secreted frizzled related protein 5 in the elderly: The Northern Shanghai Study. Clin Interv Aging. 2018; 13:389–395. doi: 10.2147/CIA.S155514
  33. Tong S, Du Y, Ji Q, et al. Expression of Sfrp5/Wnt5a in human epicardial adipose tissue and their relationship with coronary artery disease. Life Sci. 2020; 245:117338. doi: 10.1016/j.lfs.2020.117338
  34. Fan W, Si Y, Xing E, et al. Human epicardial adipose tissue inflammation correlates with coronary artery disease. Cytokine. 2023; 162:156119. doi: 10.1016/j.cyto.2022.156119
  35. Ji H, Li H, Zhuang J, et al. High serum level of secreted frizzled-related protein 5 (sfrp5) is associated with future cardiovascular events. Cardiovasc Ther. 2017;2(1): e115.
  36. An Y, Wang Q, Wang H, et al. Clinical significance of sFRP5, RBP-4 and NT-proBNP in patients with chronic heart failure. Am J Transl Res. 2021;13(6):6305–6311.
  37. Wu J, Zheng H, Liu X, et al. Prognostic Value of Secreted Frizzled-Related Protein 5 in Heart Failure Patients with and Without Type 2 Diabetes Mellitus. Circ Heart Fail. 2020;13(9): e007054. doi: 10.1161/CIRCHEARTFAILURE.120.007054
  38. Du Y, Zhao Y, Zhu Y, et al. High Serum Secreted Frizzled-Related Protein 5 Levels Associates with Early Improvement of Cardiac Function Following ST-Segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention. J Atheroscler Thromb. 2019;26(10):868–878. doi: 10.5551/jat.47019
  39. Sun S, Zhai H, Zhu M, et al. Insulin resistance is associated with Sfrp5 in obstructive sleep apnea. Braz J Otorhinolaryngol. 2019;85(6):739–745.doi: 10.1016/j.bjorl.2018.07.002
  40. Zhang H, Liu Z. Effects of Dapagliflozin in Combination with Metoprolol Sustained-Release Tablets on Prognosis and Cardiac Function in Patients with Acute Myocardial Infarction after PCI. Comput Math Methods Med. 2022; 2022:5734876. doi: 10.1155/2022/5734876
  41. Hu W, Li L, Yang M, et al. Circulating Sfrp5 is a signature of obesity-related metabolic disorders and is regulated by glucose and liraglutide in humans. J Clin Endocrinol Metab. 2013;98(1):290–298. doi: 10.1210/jc.2012-2466
  42. He X, Ma H. Correlation Between Circulating Levels of Secreted Frizzled-Related Protein 5 and Type 2 Diabetic Patients and Subjects with Impaired-Glucose Regulation. Diabetes Metab Syndr Obes. 2020;13:1243–1250.doi: 10.2147/DMSO.S242657
  43. Tan X, Wang X, Chu H, et al. SFRP5 correlates with obesity and metabolic syndrome and increases after weight loss in children. Clin Endocrinol (Oxf). 2014;81(3):363–369. doi: 10.1111/cen.12361

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Schematic representation of the cardiometabolic and cardiovascular effects of SFRP5.

Download (85KB)
Indexing metadata

Copyright (c) 2023 Alieva A.M., Teplova N.V., Baykova I.E., Voronkova K.V., Shnakhova L.M., Makeeva L.M., Kotikova I.A., Nikitin I.G.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies