Korean Circ J.  2023 Feb;53(2):92-102. 10.4070/kcj.2022.0282.

Effect of Vitamin D on YKL-40: Rat Hypercholesterolemia Model

• Kocabas R

• KMID: 2539486
• DOI: http://doi.org/10.4070/kcj.2022.0282

Abstract

Background and Objectives
YKL-40 is considered to be associated with cardiovascular disease (CVD). In this study, the effect of serum 25(OH) vitamin D [25(OH)VitD] differences between groups on YKL-40 was evaluated on a hypercholesterolemia rat model.
Methods
Thirty-two male rats (wistar albino) were equally divided into 4 groups. The first group was the control group; the second group was high-cholesterol (H-CH) adequate vitamin D (VitD) group (H-Ade^VD ). The third group was the H-CH deficient VitD group (H-Def ^VD), and the last group was designed with the H-CH supplement VitD (H-Sup^VD). The feeding process consisted of 2 stages. At the first stage (5 months), the H-Def^VD group was fed on VitD deficient chow, while the other groups (control, H-Ade^VD, H-Sup^VD) were fed on standard chow. At the second stage (3 months), the H-Ade^VDand the H-Sup^VD groups were fed on the H-CH chow, whereas the H-Def^VD group was fed on the H-CH-VitD deficient chow. Moreover, the H-Sup^VD group was given 100 IU/kg/day VitD along with the H-CH chow.
Results
Compared with the control group, interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and YKL-40 values in the H-Def^VD groups increased significantly (p<0.001, p<0.001, p=0.009, p=0.005; sequentially).
Conclusion
It can be concluded that VitD can suppress the YKL-40, thus, it will prevent CVD development in rat. Therefore, further clinical studies related with human will reveal the effect of VitD and YKL-40 on CVD development.

Keyword

Cardiovascular diseases; Chitinase 3-like protein 1 (YKL-40); Intercellular adhesion molecule-1; Vascular cell adhesion molecule-1; Vitamin D

Figure

• 

  Figure 1 Serum 25(OH)VitD values. Groups were compared using repeated-measures analysis of variance between groups and within groups values.H-AdeVD = high-cholesterol adequate vitamin D group; H-DefVD = high-cholesterol deficient vitamin D group; H-SupVD = high-cholesterol supplement vitamin D group; 25(OH)VitD = 25(OH) vitamin D.Different superscripts indicate significant difference (lowercase letters: control, H-AdeVD, H-DefVD, initial, 5th month; number: p=0.05, p=0.045, p=0.016, p=0.011, p=0.01, p=0.008, p=0.001, p<0.001).

• 

  Figure 2 Serum IL-6, sICAM1 and sVCAM1 parameter values. Groups were compared using repeated-measures analysis of variance between groups and within groups values.H-AdeVD = high-cholesterol adequate vitamin D group; H-DefVD = high-cholesterol deficient vitamin D group; H-SupVD = high-cholesterol supplement vitamin D group; IL-6 = interleukin-6; sICAM1 = soluble intercellular adhesion molecule-1; sVCAM1 = soluble vascular cell adhesion molecule-1.Different superscripts indicate significant difference (lowercase letters: control, H-AdeVD, H-DefVD, 5th month; number: p<0.05, p=0.05, p=0.005, p=0.001, p<0.001).

• 

  Figure 3 Serum YKL-40 values. Groups were compared using repeated-measures analysis of variance between groups and within groups values.H-AdeVD = high-cholesterol adequate vitamin D group; H-DefVD = high-cholesterol deficient vitamin D group; H-SupVD = high-cholesterol supplement vitamin D group.Different superscripts indicate significant difference (lowercase letters: control, H-DefVD, 5th month; number: p<0.05, p=0.055, p=0.007, p=0.005, p=0.001).

Reference

1. Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019; 139:e56–528. PMID: 30700139.

2. Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013; 88:720–755. PMID: 23790560.

3. Molinari C, Morsanuto V, Polli S, Uberti F. Cooperative effects of Q10, vitamin D₃, and L-arginine on cardiac and endothelial cells. J Vasc Res. 2018; 55:47–60. PMID: 29301117.

4. Cardoso FE, Dos Santos LD, Tenório AP, Lopes MR, Barbosa RH. Supplementation with vitamin D and its analogs for treatment of endothelial dysfunction and cardiovascular disease. J Vasc Bras. 2020; 19:e20190150. PMID: 34178073.

5. Kastrup J. Can YKL-40 be a new inflammatory biomarker in cardiovascular disease? Immunobiology. 2012; 217:483–491. PMID: 21601307.

6. Kim HM, Lee BW, Song YM, et al. Potential association between coronary artery disease and the inflammatory biomarker YKL-40 in asymptomatic patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2012; 11:84. PMID: 22809439.

7. Deng X, Zhao L, Guo C, et al. Higher serum asprosin level is associated with urinary albumin excretion and renal function in type 2 diabetes. Diabetes Metab Syndr Obes. 2020; 13:4341–4351. PMID: 33223841.

8. Kjaergaard AD, Johansen JS, Bojesen SE, Nordestgaard BG. Role of inflammatory marker YKL-40 in the diagnosis, prognosis and cause of cardiovascular and liver diseases. Crit Rev Clin Lab Sci. 2016; 53:396–408. PMID: 27187575.

9. Faridvand Y, Bagherpour-Hassanlouei N, Nozari S, et al. 1, 25-Dihydroxyvitamin D3 activates apelin/APJ system and inhibits the production of adhesion molecules and inflammatory mediators in LPS-activated RAW264.7 cells. Pharmacol Rep. 2019; 71:811–817. PMID: 31377563.

10. Liu L, Shi Z, Ji X, et al. Adipokines, adiposity, and atherosclerosis. Cell Mol Life Sci. 2022; 79:272. PMID: 35503385.

11. Beveridge LA, Khan F, Struthers AD, et al. Effect of vitamin D supplementation on markers of vascular function: a systematic review and individual participant meta-analysis. J Am Heart Assoc. 2018; 7:e008273. PMID: 29848497.

12. Abulmeaty MM, Almajwal AM, Alam I, et al. Relationship of vitamin D-deficient diet and irisin, and their impact on energy homeostasis in rats. Front Physiol. 2020; 11:25. PMID: 32082189.

13. Balci T, Kocabas R, Cuce G, Akoz M. Inhibition of fatty acid binding protein 4 in obese male mice adversely affects reproductive parameters. J Reprod Infertil. 2021; 22:16–22. PMID: 33680881.

14. Yin K, You Y, Swier V, et al. Vitamin D protects against atherosclerosis via regulation of cholesterol efflux and macrophage polarization in hypercholesterolemic swine. Arterioscler Thromb Vasc Biol. 2015; 35:2432–2442. PMID: 26381871.

15. Lee SH, Kim DH, Youn YN, et al. Effect of rosuvastatin on bovine pericardial aortic tissue valve calcification in a rat subdermal implantation model. Korean Circ J. 2017; 47:401–408. PMID: 28567091.

16. Kocabas R, Akoz M. The effects of vitamin D supplementation on healthy and hypercholesterolemic rabbits on levels of OSI and paraoxonase. Turk Biyokim Derg. 2018; 43:549–556.

17. Wang JH, Keisala T, Solakivi T, Minasyan A, Kalueff AV, Tuohimaa P. Serum cholesterol and expression of ApoAI, LXRbeta and SREBP2 in vitamin D receptor knock-out mice. J Steroid Biochem Mol Biol. 2009; 113:222–226. PMID: 19429425.

18. Soave O, Brand CD. Coprophagy in animals: a review. Cornell Vet. 1991; 81:357–364. PMID: 1954740.

19. Wolf ST, Dillon GA, Alexander LM, Jablonski NG, Kenney WL. Skin pigmentation is negatively associated with circulating vitamin D concentration and cutaneous microvascular endothelial function. Am J Physiol Heart Circ Physiol. 2022; 323:490–498. PMID: 35930446.

20. Zhou Q, Han X, Li R, et al. Anti-atherosclerosis of oligomeric proanthocyanidins from Rhodiola rosea on rat model via hypolipemic, antioxidant, anti-inflammatory activities together with regulation of endothelial function. Phytomedicine. 2018; 51:171–180. PMID: 30466614.

21. Aköz M, Kocabaş R, Topçu C, Gürbilek M. The effects of trans-9 18:1 octadecenoic acid isomer on levels of sICAM-1, svICAM-1 and IGF-1. Turk J Biochem. 2011; 36:1–5.

22. Omidian M, Mahmoudi M, Javanbakht MH, et al. Effects of vitamin D supplementation on circulatory YKL-40 and MCP-1 biomarkers associated with vascular diabetic complications: a randomized, placebo-controlled, double-blind clinical trial. Diabetes Metab Syndr. 2019; 13:2873–2877. PMID: 31425951.

23. Malyszko J, Koc-Zorawska E, Malyszko J. YKL-40, a marker of cardiovascular disease and endothelial dysfunction, in kidney transplant recipients. Transplantation Proceedings. Amsterdam: Elsevier Inc.;2014. p. 2651–2653.

24. Tong X, Wang D, Liu S, et al. The YKL-40 protein is a potential biomarker for COPD: a meta-analysis and systematic review. Int J Chron Obstruct Pulmon Dis. 2018; 13:409–418. PMID: 29430175.

25. Deng Y, Li G, Chang D, Su X. YKL-40 as a novel biomarker in cardio-metabolic disorders and inflammatory diseases. Clin Chim Acta. 2020; 511:40–46. PMID: 33002471.

26. Naeini AE, Moeinzadeh F, Vahdat S, Ahmadi A, Hedayati ZP, Shahzeidi S. The effect of Vitamin D administration on intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels in hemodialysis patients: a placebo-controlled, double-blinded clinical trial. J Res Pharm Pract. 2017; 6:16–20. PMID: 28331861.

27. Askin L, Tibilli H, Tanriverdi O, Turkmen S. The relationship between coronary artery disease and SIRT1 protein. North Clin Istanb. 2020; 7:631–635. PMID: 33381707.