Profilin as a Novel Biomarker for Assessing Atherosclerosis in Hemodialysis Patients

Aim. Studies have shown a significant correlation between atherosclerosis and profilin-1. However, there is no information in the literature on the concentration of profilin in hemodialysis (HD) patients. This research examined the association between profilin-1 and carotid intima-media thickness (CIMT), as a marker of early atherosclerosis in HD patients.
Material and methods. 50 chronic HD patients and 38 healthy, control patients were included in this study. CIMT was measured by high-resolution ultrasonography.
Results. The HD patients were older and had higher concentrations of profilin-1, C reactive protein (CRP), uric acid, parathormone, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) than the control patients. In the HD patients, variables impacting CIMT were examined. CIMT and profilin-1 were significantly correlated (r = 0.637, p <0.01), as were CIMT and age (r = 0.424, p = 0.002). Linear regression analysis revealed that profilin-1 is a significant and independent predictor of carotid intima-media thickness (CIMT). Higher profilin-1 levels were associated with increased CIMT values.
Conclusion. For the first time, it has been shown that HD patients had greater concentrations of profilin-1 than healthy controls. Also, an independent relationship between profilin-1 and CIMT in HD patients was demonstrated.

1. Deo R, Dubin RF, Ren Y, Murthy AC, Wang J, Zheng H et al. Proteomic cardiovascular risk assessment in chronic kidney disease. European Heart Journal. 2023;44(23):2095–110. DOI: 10.1093/eurheartj/ehad115

2. Bevc S, Hojs R, Ekart R, Hojs-Fabjan T. Atherosclerosis in hemodialysis patients: traditional and nontraditional risk factors. Acta Dermatovenerologica Alpina, Pannonica, Et Adriatica. 2006;15(4):151–7. PMID: 17982607

3. Choi Y, Jacobs DR, Kramer HJ, Shroff GR, Chang AR, Duprez DA. Nontraditional Risk Factors for Progression Through Chronic Kidney Disease Risk Categories: The Coronary Artery Risk Development in Young Adults Study. The American Journal of Medicine. 2023;136(4):380-389.e10. DOI: 10.1016/j.amjmed.2022.12.001

4. Lohraseb I, McCarthy P, Secker G, Marchant C, Wu J, Ali N et al. Global ubiquitinome profiling identifies NEDD4 as a regulator of Profilin 1 and actin remodelling in neural crest cells. Nature Communications. 2022;13(1):2018. DOI: 10.1038/s41467-022-29660-3

5. Read T-A, Cisterna BA, Skruber K, Ahmadieh S, Lindamood HL, Vitriol JA et al. The actin binding protein profilin 1 is critical for mitochondria function. bioRxiv. 2023. [Av. at: https://www.biorxiv.org/content/10.1101/2023.08.07.552354v4]

6. Paszek E, Zajdel W, Rajs T, Żmudka K, Legutko J, Kleczyński P. Profilin 1 and Mitochondria—Partners in the Pathogenesis of Coronary Artery Disease? International Journal of Molecular Sciences. 2021;22(3):1100. DOI: 10.3390/ijms22031100

7. Allen A, Gau D, Roy P. The role of profilin-1 in cardiovascular diseases. Journal of Cell Science. 2021;134(9):jcs249060. DOI: 10.1242/jcs.249060

8. Nezu T, Hosomi N, Aoki S, Matsumoto M. Carotid Intima-Media Thickness for Atherosclerosis. Journal of Atherosclerosis and Thrombosis. 2016;23(1):18–31. DOI: 10.5551/jat.31989

9. Spence JD. Assessment of atherosclerosis: should coronary calcium score and intima-media thickness be replaced by ultrasound measurement of carotid plaque burden and vessel wall volume? Current Opinion in Lipidology. 2023;34(3):126–32. DOI: 10.1097/MOL.0000000000000880

10. Mukherjee R, Bhattacharya R, Naiya SB, Mondal SS, Lyngdoh L. Assessment of Atherosclerosis in Sle Patients by Measuring Carotid Intima Media Thickness: A Cross Sectional Study. The Journal of the Association of Physicians of India. 2022;70(4):11–2. PMID: 35443433

11. Zhu X, Jing R, Li X, Zhang W, Tang Y, Liu T. Left ventricular hypertrophy, carotid atherosclerosis, and cognitive impairment in peritoneal dialysis patients. BMC Cardiovascular Disorders. 2023;23(1):127. DOI: 10.1186/s12872-023-03130-0

12. Karaer Büberci R, Öztekin PS, Duranay M. The relationship between apelin and carotid intima media thickness, and the presence of plaque in dialysis patients. Seminars in Dialysis. 2022;35(4):337–42. DOI: 10.1111/sdi.13052

13. Vlad C, Burlacu A, Florea L, Artene B, Badarau S, Covic A et al. A comprehensive review on apolipoproteins as nontraditional cardiovascular risk factors in end-stage renal disease: current evidence and perspectives. International Urology and Nephrology. 2019;51(7):1173–89. DOI: 10.1007/s11255-019-02170-w

14. Caglayan E, Romeo GR, Kappert K, Odenthal M, Südkamp M, Body SC et al. Profilin-1 Is Expressed in Human Atherosclerotic Plaques and Induces Atherogenic Effects on Vascular Smooth Muscle Cells. PLoS ONE. 2010;5(10):e13608. DOI: 10.1371/journal. pone.0013608

15. An M-H, Choi S-M, Lee P-H, Park S, Baek AR, Jang A-S. Cofilin-1 and profilin-1 expression in lung microvascular endothelial cells exposed to titanium dioxide nanoparticles. Advances in Clinical and Experimental Medicine. 2022;31(11):1255–64. DOI: 10.17219/acem/152032

16. Gau D, Daoud A, Allen A, Joy M, Sagan A, Lee S et al. Vascular endothelial profilin-1 drives a protumorigenic tumor microenvironment and tumor progression in renal cancer. Journal of Biological Chemistry. 2023;299(8):105044. DOI: 10.1016/j.jbc.2023.105044

17. Ding H, Chen B, Lu Q, Wang J. Profilin-1 mediates microvascular endothelial dysfunction in diabetic retinopathy through HIF-1α-dependent pathway. International Journal of Clinical and Experimental Pathology. 2018;11(3):1247–55. PMID: 31938219

18. Ramaiola I, Padró T, Peña E, Juan-Babot O, Cubedo J, Martin-Yuste V et al. Changes in thrombus composition and profilin-1 release in acute myocardial infarction. European Heart Journal. 2015;36(16):965–75. DOI: 10.1093/eurheartj/ehu356

19. Romeo GR, Moulton KS, Kazlauskas A. Attenuated Expression of Profilin-1 Confers Protection From Atherosclerosis in the LDL Receptor–Null Mouse. Circulation Research. 2007;101(4):357–67. DOI: 10.1161/CIRCRESAHA.107.151399

20. Eroglu E, Unal HU, Guclu A, Kocyigit I, Karaman M, Saglam M et al. The association of profilin‐1 levels with survival in chronic kidney disease. European Journal of Clinical Investigation. 2017;47(12):e12839. DOI: 10.1111/eci.12839

21. Diaz A, Bia D, Zócalo Y, Manterola H, Larrabide I, Lo Vercio L et al. Carotid Intima Media Thickness Reference Intervals for a Healthy Argentinean Population Aged 11–81 Years. International Journal of Hypertension. 2018;2018:1–13. DOI: 10.1155/2018/8086714

22. Heiss G, Sharrett AR, Barnes R, Chambless LE, Szklo M, Alzola C. Carotid Atherosclerosis Measured by B-Mode Ultrasound in Populations: Associations with Cardiovascular Risk Factors in the ARIC Study. American Journal of Epidemiology. 1991;134(3):250–6. DOI: 10.1093/oxfordjournals.aje.a116078