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Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population

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Abstract

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case–control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor—CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29–16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23–7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01–1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07–0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05–0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.

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References

  1. Jafari Salim S, Alizadeh S, Djalali M, Nematipour E, Hassan Javanbakht M (2017) Effect of omega-3 polyunsaturated fatty acids supplementation on body composition and circulating levels of follistatin-like 1 in males with coronary artery disease: a randomized double-blind clinical trial. Am J Mens Health 11(6):1758–1764

    Article  PubMed  PubMed Central  Google Scholar 

  2. WHO (2021) https://www.who.int/news/item/25-08-2021-more-than-700-million-people-with-untreated-hypertension. (Accessed: 18 May 2023)

  3. Xu X, Zhang T, Mokou M, Li L, Li P, Song J, Liu H, Zhu Z, Liu D, Yang M, Yang G (2020) Follistatin-like 1 as a novel adipomyokine related to insulin resistance and physical activity. J Clin Endocrinol Metab 105(12):dgaa629

    Article  PubMed  Google Scholar 

  4. Murillo-González FE, Ponce-Ruiz N, Rojas-García AE, Rothenberg SJ, Bernal-Hernández YY, Cerda-Flores RM, Mackness M, Barrón-Vivanco BS, González-Arias CA, Ponce-Gallegos J, Medina-Díaz IM (2020) PON1 lactonase activity and its association with cardiovascular disease. Clin Chim Acta 500:47–53

    Article  PubMed  Google Scholar 

  5. Ponce-Ruiz N, Murillo-González FE, Rojas-García AE, Barrón-Vivanco BS, Bernal-Hernández YY, González-Arias CA, Ortega-Cervantes L, Ponce-Gallegos J, López-Guarnido O, Medina-Díaz IM (2020) PON1 status and homocysteine levels as potential biomarkers for cardiovascular disease. Exp Gerontol 140:111062

    Article  CAS  PubMed  Google Scholar 

  6. El-Armouche A, Ouchi N, Tanaka K, Doros G, Wittköpper K, Schulze T, Eschenhagen T, Walsh K, Sam F (2011) Follistatin-like 1 in chronic systolic heart failure: a marker of left ventricular remodeling. Circ Heart Fail 4:621–627

    Article  PubMed  PubMed Central  Google Scholar 

  7. Tanaka K, Valero-Muñoz M, Wilson RM, Essick EE, Fowler CT, Nakamura K, van den Hoff M, Ouchi N, Sam F (2016) Follistatin like 1 regulates hypertrophy in heart failure with preserved ejection fraction. JACC Basic Transl Sci 1:207–221

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hu S, Liu H, Hu Z, Li L, Yang Y (2020) Follistatin-like 1: a dual regulator that promotes cardiomyocyte proliferation and fibrosis. J Cell Physiol 235(9):5893–5902

    Article  CAS  PubMed  Google Scholar 

  9. Qi C, Song X, Wang H, Yan Y, Liu B (2022) The role of exercise-induced myokines in promoting angiogenesis. Front Physiol 13:981577

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ogura Y, Ouchi N, Ohashi K, Shibata R, Kataoka Y, Kambara T, Kito T, Maruyama S, Yuasa D, Matsuo K, Enomoto T, Uemura Y, Miyabe M, Ishii M, Yamamoto T, Shimizu Y, Walsh K, Murohara T (2012) Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical models. Circulation 126:1728–1738

    Article  PubMed  PubMed Central  Google Scholar 

  11. Seki M, Powers JC, Maruyama S, Zuriaga MA, Wu CL, Kurishima C, Kim L, Johnson J, Poidomani A, Wang T, Muñoz E, Rajan S, Park JY, Walsh K, Recchia FA (2018) Acute and chronic increases of circulating FSTL1 normalize energy substrate metabolism in pacing-induced heart failure. Circ Heart Fail 11(1):e004486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Peters MC, Di Martino S, Boelens T, Qin J, van Mil A, Doevendans PA, Chamuleau SAJ, Sluijter JPG, Neef K (2022) Follistatin-like 1 promotes proliferation of matured human hypoxic iPSC-cardiomyocytes and is secreted by cardiac fibroblasts. Mol Ther Methods Clin Dev 25:3–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Inoue K, Fujie S, Horii N, Yamazaki H, Uchida M, Iemitsu M (2022) Aerobic exercise training-induced follistatin-like 1 secretion in the skeletal muscle is related to arterial stiffness via arterial NO production in obese rats. Physiol Rep 10(10):e15300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Maruyama S, Nakamura K, Papanicolaou KN, Sano S, Shimizu I, Asaumi Y, Hoff MJ, Ouchi N, Recchia FA, Walsh K (2016) Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture. EMBO Mol Med 8(8):949–966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wei K, Serpooshan V, Hurtado C, Diez-Cuñado M, Zhao M, Maruyama S, Zhu W, Fajardo G, Noseda M, Nakamura K, Tian X, Liu Q, Wang A, Matsuura Y, Bushway P, Cai W, Savchenko A, Mahmoudi M, Schneider MD, van den Hoff MJ, Ruiz-Lozano P (2015) Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature 525(7570):479–485

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  16. DeLong DM, DeLong ER, Wood PD, Lippel K, Rifkind BM (1986) A comparison of methods for the estimation of plasma low- and very low-density lipoprotein cholesterol. The lipid research clinics prevalence study. JAMA 256(17):2372–2377

    Article  CAS  PubMed  Google Scholar 

  17. Eckerson HW, Wyte CM, La Du BN (1983) The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet 35(6):1126–1138

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Billecke S, Draganov D, Counsell R, Stetson P, Watson C, Hsu C, La Du BN (2000) Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos 28(11):1335–1342

    CAS  PubMed  Google Scholar 

  19. Hadaegh F, Harati H, Ghanbarian A, Azizi F (2006) Association of total cholesterol versus other serum lipid parameters with the short-term prediction of cardiovascular outcomes: Tehran lipid and glucose study. Eur J Cardiovasc Prev Rehabil 13(4):571–577

    Article  PubMed  Google Scholar 

  20. Hedayatnia M, Asadi Z, Zare-Feyzabadi R, Yaghooti-Khorasani M, Ghazizadeh H, Ghaffarian-Zirak R, Nosrati-Tirkani A, Mohammadi-Bajgiran M, Rohban M, Sadabadi F, Rahimi HR, Ghalandari M, Ghaffari MS, Yousefi A, Pouresmaeili E, Besharatlou MR, Moohebati M, Ferns GA, EsmailyH G-M (2020) Dyslipidemia and cardiovascular disease risk among the MASHAD study population. Lipids Health Dis 19(1):42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Goldfine AB, Kaul S, Hiatt WR (2011) Fibrates in the treatment of dyslipidemias–time for a reassessment. N Engl J Med 365(6):481–484

    Article  CAS  PubMed  Google Scholar 

  22. Kim NH, Kim SG (2020) Fibrates revisited: potential role in cardiovascular risk reduction. Diabetes Metab J 44(2):213–221

    Article  MathSciNet  PubMed  PubMed Central  Google Scholar 

  23. Horak M, Kuruczova D, Zlamal F, Tomandl J, Bienertova-Vasku J (2018) Follistatin-like 1 is downregulated in morbidly and super obese central-european population. Dis Markers 2018:4140815

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lee SY, Kim DY, Kyung Kwak M, Hee Ahn S, Kim H, Kim BJ, Koh JM, Rhee Y, Hwa Kim C, Hyun Baek K, Min YK, Hun Lee S, Kang MI (2019) High circulating follistatin-like protein 1 as a biomarker of a metabolically unhealthy state. Endocr J 66(3):241–251

    Article  CAS  PubMed  Google Scholar 

  25. Aikawa T, Shimada K, Miyauchi K, Miyazaki T, Sai E, Ouchi S, Kadoguchi T, Kunimoto M, Joki Y, Dohi T, Okazaki S, Isoda K, Ohashi K, Murohara T, Ouchi N, Daida H (2019) Associations among circulating levels of follistatin-like 1, clinical parameters, and cardiovascular events in patients undergoing elective percutaneous coronary intervention with drug-eluting stents. PLoS ONE 14(4):e0216297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ryanto GRT, Musthafa A, Hara T, Emoto N (2023) Inactivating the uninhibited: the tale of activins and inhibins in pulmonary arterial hypertension. Int J Mol Sci 24(4):3332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fan N, Sun H, Wang Y, Wang Y, Zhang L, Xia Z, Peng L, Hou Y, Shen W, Liu R, Yin J, Peng Y (2013) Follistatin-like 1: a potential mediator of inflammation in obesity. Mediators Inflamm 2013:752519

    Article  PubMed  PubMed Central  Google Scholar 

  28. Horak M, Fairweather D, Kokkonen P, Bednar D, Bienertova-Vasku J (2022) Follistatin-like 1 and its paralogs in heart development and cardiovascular disease. Heart Fail Rev 27(6):2251–2265

    Article  CAS  PubMed  Google Scholar 

  29. Wu YS, Zhu B, Luo AL, Yang L, Yang C (2018) The role of cardiokines in heart diseases: beneficial or detrimental? Biomed Res Int 2018:8207058

    PubMed  PubMed Central  Google Scholar 

  30. Leach NV, Dronca E, Vesa SC, Sampelean DP, Craciun EC, Lupsor M, Crisan D, Tarau R, Rusu R, Para I, Grigorescu M (2014) Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis. Eur J Intern Med 25(8):762–767

    Article  CAS  PubMed  Google Scholar 

  31. Ganguly P, Alam SF (2015) Role of homocysteine in the development of cardiovascular disease. Nutr J 14:6

    Article  PubMed  PubMed Central  Google Scholar 

  32. Guidara W, Messedi M, Naifar M, Charfi N, Grayaa S, Maalej M, Maalej M, Ayadi F (2022) Predictive value of oxidative stress biomarkers in drug-free patients with bipolar disorder. Nord J Psychiatry 76(7):539–550

    Article  PubMed  Google Scholar 

  33. Hayakawa S, Ohashi K, Shibata R, Takahashi R, Otaka N, Ogawa H, Ito M, Kanemura N, Hiramatsu-Ito M, Ikeda N, Murohara T, Ouchi N (2016) Association of circulating follistatin-like 1 levels with inflammatory and oxidative stress markers in healthy men. PLoS ONE 11(5):e0153619

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ravaglia G, Forti P, Maioli F, Servadei L, Martelli M, Arnone G, Talerico T, Zoli M, Mariani E (2004) Plasma homocysteine and inflammation in elderly patients with cardiovascular disease and dementia. Exp Gerontol 39(3):443–450

    Article  CAS  PubMed  Google Scholar 

  35. Angayarkanni N, Barathi S, Seethalakshmi T, Punitham R, Sivaramakrishna R, Suganeswari G, Tarun S (2008) Serum PON1 arylesterase activity in relation to hyperhomocysteinaemia and oxidative stress in young adult central retinal venous occlusion patients. Eye 22(7):969–974

    Article  CAS  PubMed  Google Scholar 

  36. Bourgonje MF, Abdulle AE, Kieneker LM, la Bastide-van GS, Bakker SJL, Gansevoort RT, Gordijn SJ, van Goor H, Bourgonje AR (2023) A sex-specific comparative analysis of oxidative stress biomarkers predicting the risk of cardiovascular events and all-cause mortality in the general population: a prospective cohort study. Antioxidants (Basel) 12(3):690

    Article  CAS  PubMed  Google Scholar 

  37. Shridas P, Tannock LR (2019) Role of serum amyloid A in atherosclerosis. Curr Opin Lipidol 30(4):320–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chistiakov DA, Melnichenko AA, Orekhov AN, Bobryshev YV (2017) Paraoxonase and atherosclerosis-related cardiovascular diseases. Biochimie 132:19–27

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful for the support received from the medical personnel of the Instituto Mexicano del Seguro Social (IMSS) in Nayarit, México, and from the Instituto Nacional de Cardiología-Ignacio Chávez, D.F. México.

Funding

This study was supported by CONACyT Grant SSA/IMSS/ISSSTE-233745 and Strengthening Research [UAN-2022].

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Authors and Affiliations

  1. Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado, Universidad Autónoma de Nayarit, Tepic, Nayarit, 63000, México

    N. Ponce-Ruíz, J. F. Herrera-Moreno, A. E. Rojas-García, B. S. Barrón-Vivanco, C. A. González-Arias, Y. Y. Bernal-Hernández, L. Ortega-Cervantes & I. M. Medina-Díaz

  2. Hospital Puerta de Hierro, Tepic, Nayarit, México

    J. Ponce-Gallegos

  3. Centro Nayarita de Innovación y Transferencia de Tecnología, Tepic, Nayarit, México

    N. Ponce-Ruíz

  4. Licenciatura en Químico Farmacobiólogo, Universidad Autónoma de Nayarit, Tepic, Nayarit, México

    J. A. Hernández-Nolasco

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  1. N. Ponce-Ruíz
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  2. J. F. Herrera-Moreno
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  10. I. M. Medina-Díaz
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Contributions

Author contributions to the paper were as follows: methodology, NP-R, IMM-D, JFH-M and JH-N; formal analysis, NP-R, JFH-M, AER-G, BSB-V and IMM-D; investigation, CAG-A, YYB-H, LO-C, JP-G, and JH-N; writing—original draft preparation, NP-R, JFH-M, AER-G and IMM-D.

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Correspondence to I. M. Medina-Díaz.

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The authors declare that they have no conflicts of interest to report.

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The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and it was approved by the ethics committee of the Hospital Antonio González Guevara, Tepic Nayarit, Mexico (registry number COMBIOET/ 05/13).

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Informed consent was obtained from all subjects involved in the study.

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Ponce-Ruíz, N., Herrera-Moreno, J.F., Rojas-García, A.E. et al. Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population. Heart Vessels (2024). https://doi.org/10.1007/s00380-024-02364-y

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