Vasodilator effect of omentin on rat aorta and mesenteric artery: is it mediated by rho-kinase (ROCK)?

Öz

Aim: One of the aims of this study was to determine whether the increased Rho kinase (ROCK) activation in various pathophysiological diseases changes after Omentin application, and to reveal whether it could be a biomarker candidate. Another aim was to determine the vasodilator effect of omentin on the aorta and superior mesenteric arteries and dose-response relationship of this effect. Method: In the study, the vasodilator effect of Omentin was shown in both aorta and mesenteric artery in isolated organ bath at doses of 1, 3, 10, 30, 100 and 300 ng/ml. Whether Omentin changed ROCK enzyme activity was shown by Elisa analysis in both aorta and mesenteric artery with 30 ng/ml Omentin dose. Results: The percentage vasodilator effect of omentin was found to be 18.434±4.54 for 1ng/ml, 32.009±7.14 for 3ng/ml, 48.268±6.35 for 10ng/ml, 54.42±8.26 for 30ng/ml, 54.673±7.61 for 100ng/ml, and 61.218±8.80 for 300ng/ml. In the mesenteric artery, it was found to be 6.044±2.55 for 1ng/ml, 23.763±5.266 for 3ng/ml, 40.050±6.122 for 10ng/ml, 51.972±7.471 for 30ng/ml, and 62.378±7.084 for 100ng/ml. EC50 values were determined as 5.81 ± 3.69 ng/ml for Omentin and 8.95 ± 11.69 ng/ml for L-NAME + Omentin. No relationship was found between Omentin and ROCK in terms of vascular vasoactivity. Conclusion: Although omentin is a promising adipokine for preventing and/or correcting hypertension, which occurs as a complication of diseases such as obesity and diabetes, further clinical and preclinical studies are needed.

Anahtar Kelimeler

• Adipose tissue
• L-NAME
• omentin
• ROCK
• vasodilator

Sıçan Aortası ve Mezenterik Arterinde Omentinin Vazodilatör Etkisi: Rho-Kinaz (ROCK) Aracılık Eder Mi?

Öz

Amaç: Bu çalışmanın amaçlarından bir tanesi, çeşitli patofizyolojik hastalıklarda artan Rho kinaz (ROCK) aktivasyonunun Omentin uygulaması sonrası değişip değişmediğini gösterip bir biyobelirteç adayı olup olmayacağını ortaya koymak. Bir diğer amacımız ise omentinin aorta ve süperior mezenterik arterlerde vazodilatör etkisi ve bu etkinin maksimum konsantrasyon doğrusunun belirlenmesidir. Yöntem: Çalışmada, Omentinin vazodilatör etkisi 1, 3, 10, 30, 100 ve 300 ng/ml dozlarında izole organ banyosunda hem aorta hem de mezenterik arterde gösterilmiştir. Omentinin ROCK enzimi aktivitesini değiştirip değiştirmediği ise 30 ng/ml Omentin dozu ile hem aortada hem de mezenterik arterde Elisa analizi ile gösterilmiştir. Bulgular: Omentin yüzde vazodilatör etkisi, 1ng/ml: için 18.434±4.54, 3ng/ml için 32.009±7.14, 10ng/ml için 48.268±6.35, 30ng/ml için 54.42±8.26, 100ng/ml için 54.673±7.61 ve 300ng/ml için 61.218±8.80 bulunmuştur. Mezenterik arterde, 1ng/ml: için 6.044±2.55, 3ng/ml için 23.763±5.266, 10ng/ml için 40,050±6,122, 30ng/ml için 51.972±7.471 ve 100ng/ml için 62.378±7.084 bulunmuştur. EC50 değerleri ise Omentin için 5.81 ± 3.69 ng/ml L-NAME + Omentin için ise 8.95 ± 11.69 ng/ml olarak tespit edilmiştir. Omentin ile ROCK arasında damar vazoaktivitesi yönünden bir ilişki bulunmamıştır. Sonuç: Omentinin, obezite, diyabet gibi hastalıkların bir komplikasyonu olarak ortaya çıkan hipertansiyonu önlemeye ve/veya düzeltmeye yönelik umut vaat eden bir adipokin olmakla birlikte daha fazla klinik ve preklinik çalışmalara ihtiyaç duyulmaktadır.

Anahtar Kelimeler

• Adipoz doku
• L-NAME
• omentin
• ROCK
• vazodilatör

Kaynakça

1. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. Mar 25 2010;316(2):129-39. doi:10.1016/j.mce.2009.08.018
2. Yang RZ, Lee MJ, Hu H, et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab. Jun 2006;290(6):E1253-61. doi:10.1152/ajpendo.00572.2004
3. Watanabe T, Watanabe-Kominato K, Takahashi Y, Kojima M, Watanabe R. Adipose Tissue-Derived Omentin-1 Function and Regulation. Compr Physiol. Jun 18 2017;7(3):765-781. doi:10.1002/cphy.c160043
4. Fain JN, Sacks HS, Buehrer B, et al. Identification of omentin mRNA in human epicardial adipose tissue: comparison to omentin in subcutaneous, internal mammary artery periadventitial and visceral abdominal depots. Int J Obes (Lond). May 2008;32(5):810-5. doi:10.1038/sj.ijo.0803790
5. Pan HY, Guo L, Li Q. Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes Res Clin Pract. Apr 2010;88(1):29-33. doi:10.1016/j.diabres.2010.01.013
6. Herder C, Ouwens DM, Carstensen M, et al. Adiponectin may mediate the association between omentin, circulating lipids and insulin sensitivity: results from the KORA F4 study. Eur J Endocrinol. Apr 2015;172(4):423-32. doi:10.1530/eje-14-0879
7. de Souza Batista CM, Yang RZ, Lee MJ, et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes. Jun 2007;56(6):1655-61. doi:10.2337/db06-1506
8. Elsaid NH, Sadik NA, Ahmed NR, Fayez SE, Mohammed NAE. Serum omentin-1 levels in type 2 diabetic obese women in relation to glycemic control, insulin resistance and metabolic parameters. J Clin Transl Endocrinol. Sep 2018;13:14-19. doi:10.1016/j.jcte.2018.05.003

9. Pan X, Kaminga AC, Wen SW, Acheampong K, Liu A. Omentin-1 in diabetes mellitus: A systematic review and meta-analysis. PLoS One. 2019;14(12):e0226292. doi:10.1371/journal.pone.0226292
10. Hiramatsu-Ito M, Shibata R, Ohashi K, et al. Omentin attenuates atherosclerotic lesion formation in apolipoprotein E-deficient mice. Cardiovasc Res. May 1 2016;110(1):107-17. doi:10.1093/cvr/cvv282
11. Sena CM. Omentin: A Key Player in Glucose Homeostasis, Atheroprotection, and Anti-Inflammatory Potential for Cardiovascular Health in Obesity and Diabetes. Biomedicines. Jan 26 2024;12(2)doi:10.3390/biomedicines12020284
12. Kazama K, Okada M, Hara Y, Yamawaki H. A novel adipocytokine, omentin, inhibits agonists-induced increases of blood pressure in rats. J Vet Med Sci. 2013;75(8):1029-34. doi:10.1292/jvms.12-0537
13. Sena CM, Pereira AM, Seiça R. Endothelial dysfunction - a major mediator of diabetic vascular disease. Biochim Biophys Acta. Dec 2013;1832(12):2216-31. doi:10.1016/j.bbadis.2013.08.006
14. Yamawaki H, Tsubaki N, Mukohda M, Okada M, Hara Y. Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochem Biophys Res Commun. Mar 19 2010;393(4):668-72. doi:10.1016/j.bbrc.2010.02.053
15. Qi D, Tang X, He J, et al. Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism. Cell Death & Disease. 2016/09/01 2016;7(9):e2360-e2360. doi:10.1038/cddis.2016.265
16. Greulich S, Chen WJ, Maxhera B, et al. Cardioprotective properties of omentin-1 in type 2 diabetes: evidence from clinical and in vitro studies. PLoS One. 2013;8(3):e59697. doi:10.1371/journal.pone.0059697
17. Çarçak N, Yavuz M, Eryiğit Karamahmutoğlu T, et al. Suppressive effect of Rho-kinase inhibitors Y-27632 and fasudil on spike-and-wave discharges in genetic absence epilepsy rats from Strasbourg (GAERS). Naunyn Schmiedebergs Arch Pharmacol. Nov 2018;391(11):1275-1283. doi:10.1007/s00210-018-1546-9
18. Tiftik RN, Erol A, Cnar MG, et al. Nitric oxide does not downregulate Rho-kinase (ROCK-2) expression in rat coronary endothelial cells. J Cardiovasc Pharmacol. Feb 2008;51(2):140-7. doi:10.1097/FJC.0b013e31815e4089
19. Amano M, Nakayama M, Kaibuchi K. Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity. Cytoskeleton (Hoboken). Sep 2010;67(9):545-54. doi:10.1002/cm.20472
20. Levent A, Büyükafsar K. Expression of Rho-kinase (ROCK-1 and ROCK-2) and its substantial role in the contractile activity of the sheep ureter. Br J Pharmacol. Oct 2004;143(3):431-7. doi:10.1038/sj.bjp.0705961
21. Büyükafşar K, Arikan O, Ark M, Kubat H, Ozveren E. Upregulation of Rho-kinase (ROCK-2) expression and enhanced contraction to endothelin-1 in the mesenteric artery from lipopolysaccharide-treated rats. Eur J Pharmacol. Sep 13 2004;498(1-3):211-7. doi:10.1016/j.ejphar.2004.07.092
22. Büyükafşar K, Yalçin I, Kurt AH, Tiftik RN, Sahan-Firat S, Aksu F. Rho-kinase inhibitor, Y-27632, has an antinociceptive effect in mice. Eur J Pharmacol. Jul 10 2006;541(1-2):49-52. doi:10.1016/j.ejphar.2006.04.042
23. Ün İ, Kurt AH, Büyükafşar K. Hyperosmolar glucose induces vasoconstriction through Rho/Rho-kinase pathway in the rat aorta. Fundam Clin Pharmacol. Jun 2013;27(3):244-51. doi:10.1111/j.1472-8206.2011.01014.x
24. Ratter-Rieck JM, Shi M, Suhre K, et al. Omentin associates with serum metabolite profiles indicating lower diabetes risk: KORA F4 Study. BMJ Open Diabetes Res Care. Mar 4 2024;12(2)doi:10.1136/bmjdrc-2023-003865
25. Leandro A, Queiroz M, Azul L, Seiça R, Sena CM. Omentin: A novel therapeutic approach for the treatment of endothelial dysfunction in type 2 diabetes. Free Radic Biol Med. Jan 2021;162:233-242. doi:10.1016/j.freeradbiomed.2020.10.021
26. Czechowski P, Hagemann T, Ghosh A, et al. Expression of Intelectin-1, also known as Omentin-1, is related to clinical phenotypes such as overweight, obesity, insulin resistance, and changes after bariatric surgery. Sci Rep. Sep 27 2024;14(1):22286. doi:10.1038/s41598-024-72720-5
27. Okamura Y, Adachi K, Niijima R, et al. Human omentin-1 reduces vascular insulin resistance and hypertension in Otsuka Long-Evans Tokushima Fatty rats. Naunyn Schmiedebergs Arch Pharmacol. May 2024;397(5):3379-3387. doi:10.1007/s00210-023-02795-w
28. Deng X, Luo H, He J, Deng W, Wang D. Omentin-1 ameliorates pulmonary arterial hypertension by inhibiting endoplasmic reticulum stress through AMPKα signaling. Clin Exp Hypertens. Dec 31 2024;46(1):2332695. doi:10.1080/10641963.2024.2332695
29. Omur SE, Cerik IB, Tekin G. Fetuin‑A, Omentin‑1 ve Chemerin'in Kalp Yetmezliğinde Sol Ventrikül Ejeksiyon Fraksiyonu ile İlişkisi. International Journal of Cardiovascular Academy. 2021/12 2021;7(4):111-118. doi:10.4103/ijca.ijca_36_21
30. Karabacak Hİ, Atalik EK, BariŞKaner H, Çiçek E. Tavşan torasik aortasinda ACh, ATP ve NA'E bağli cevaplara L-NAME'İN etkisi The Effect Of L-NAME On Responses Due To ACh, ATP And NA in Rabbit Thorack Aorta. Selçuk Tıp Dergisi. 1996;12(4):377-382.
31. Khalil RA. Regulation of Vascular Smooth Muscle Function. 2010. Integrated Systems Physiology: From Molecule to Function.
32. Sopko NA, Hannan JL, Bivalacqua TJ. Understanding and targeting the Rho kinase pathway in erectile dysfunction. Nature Reviews Urology. 2014/11/01 2014;11(11):622-628. doi:10.1038/nrurol.2014.278