Impact of Tofacitinib and Aspirin on Lipoprotein Levels in Type 2 diabetic Rats: Implications for Macrovascular Complications’ Risk Mitigation
DOI:
https://doi.org/10.56919/usci.2433.018Keywords:
cardiovascular diseases, inflammation, lipoproteins, macrovascular complications, type 2 diabetesAbstract
Study’s Excerpt/Novelty
- This study introduces an approach of using tofacitinib and aspirin to target both lipoprotein metabolism and inflammation in a type 2 diabetic rat model.
- By demonstrating significant improvements in lipid profiles and reductions in atherogenic indices, particularly at higher doses, this research highlighted the potential of these drugs to mitigate cardiovascular risks associated with type 2 diabetes.
- The findings provide a foundation for future exploration of anti-inflammatory strategies in managing dyslipidemia and macrovascular complications in diabetic conditions.
Full Abstract
Diabetes type 2 (T2D) related macrovascular complications are frequently linked to lipoprotein metabolism and the activation of inflammatory pathways. This study explores the impact of tofacitinib and aspirin on lipoprotein levels and inflammation in type 2 diabetic rats. Ten groups of eight rats each were treated with varying doses of tofacitinib and aspirin for nine weeks following induction of diabetes. Significant decreases in triglycerides, cholesterol, and LDL (P<0.05) were observed, along with increases in HDL levels, particularly at higher doses of tofacitinib 20 mg/kg and aspirin 200 mg/kg when compared with the diabetic control group. Additionally, treatment with both drugs at different doses significantly (P<0.05) reduced the artherogenic indices (CRI-I, CRI-II, AIP, AC), suggesting a decreased future risk of cardiovascular disease. These results highlight the possibility of addressing inflammation to reduce cardiovascular risk and dyslipidemia in rats with type 2 diabetes.
References
Agrawal, N. K., & Kant, S. (2014). Targeting inflammation in diabetes: Newer therapeutic options. World J Diabetes, 5(5), 697-710. https://doi.org/10.4239/wjd.v5.i5.697
Althaher, A. R. (2022). An Overview of Hormone-Sensitive Lipase (HSL). ScientificWorldJournal, 2022, 1964684. https://doi.org/10.1155/2022/1964684
Alves-Bezerra, M., & Cohen, D. E. (2017). Triglyceride Metabolism in the Liver. Compr Physiol, 8(1), 1-8. https://doi.org/10.1002/cphy.c170012
Bako, H. Y., Ibrahim, M. A., Isah, M. S., & Ibrahim, S. (2019). Inhibition of JAK-STAT and NF-κB signalling systems could be a novel therapeutic target against insulin resistance and type 2 diabetes. Life Sci, 239, 117045. https://doi.org/10.1016/j.lfs.2019.117045
Bonilha, I., Zimetti, F., Zanotti, I., Papotti, B., & Sposito, A. C. (2021). Dysfunctional High-Density Lipoproteins in Type 2 Diabetes Mellitus: Molecular Mechanisms and Therapeutic Implications. J Clin Med, 10(11). https://doi.org/10.3390/jcm10112233
Cerf, M. E. (2013). Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne), 4, 37. https://doi.org/10.3389/fendo.2013.00037
Chan, J. C. N., Lim, L. L., Wareham, N. J., Shaw, J. E., Orchard, T. J., Zhang, P., Lau, E. S. H., Eliasson, B., Kong, A. P. S., Ezzati, M., Aguilar-Salinas, C. A., McGill, M., Levitt, N. S., Ning, G., So, W. Y., Adams, J., Bracco, P., Forouhi, N. G., Gregory, G. A., Guo, J., Hua, X., Klatman, E. L., Magliano, D. J., Ng, B. P., Ogilvie, D., Panter, J., Pavkov, M., Shao, H., Unwin, N., White, M., Wou, C., Ma, R. C. W., Schmidt, M. I., Ramachandran, A., Seino, Y., Bennett, P. H., Oldenburg, B., Gagliardino, J. J., Luk, A. O. Y., Clarke, P. M., Ogle, G. D., Davies, M. J., Holman, R. R., & Gregg, E. W. (2021). The Lancet Commission on diabetes: using data to transform diabetes care and patient lives. Lancet, 396(10267), 2019-2082. https://doi.org/10.1016/s0140-6736(20)32374-6
Deng, C. F., Zhu, N., Zhao, T. J., Li, H. F., Gu, J., Liao, D. F., & Qin, L. (2022). Involvement of LDL and ox-LDL in Cancer Development and Its Therapeutical Potential. Front Oncol, 12, 803473. https://doi.org/10.3389/fonc.2022.803473
Farbstein, D., & Levy, A. P. (2012). HDL dysfunction in diabetes: causes and possible treatments. Expert Rev Cardiovasc Ther, 10(3), 353-361. https://doi.org/10.1586/erc.11.182
Haas, M. E., Attie, A. D., & Biddinger, S. B. (2013). The regulation of ApoB metabolism by insulin. Trends Endocrinol Metab, 24(8), 391-397. https://doi.org/10.1016/j.tem.2013.04.001
Jaichander, P., Selvarajan, K., Garelnabi, M., & Parthasarathy, S. (2008). Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin. J Lipid Res, 49(10), 2142-2148. https://doi.org/10.1194/jlr.M800082-JLR200
Kim, S. H., Cho, Y. K., Kim, Y.-J., Jung, C. H., Lee, W. J., Park, J.-Y., Huh, J. H., Kang, J. G., Lee, S. J., & Ihm, S.-H. (2022). Association of the atherogenic index of plasma with cardiovascular risk beyond the traditional risk factors: a nationwide population-based cohort study. Cardiovascular Diabetology, 21(1), 81. https://doi.org/10.1186/s12933-022-01522-8
Kluck, G. E. G., Durham, K. K., Yoo, J. A., & Trigatti, B. L. (2020). High Density Lipoprotein and Its Precursor Protein Apolipoprotein A1 as Potential Therapeutics to Prevent Anthracycline Associated Cardiotoxicity. Front Cardiovasc Med, 7, 65. https://doi.org/10.3389/fcvm.2020.00065
Liu, T., Zuo, R., Wang, J., Huangtao, Z., Wang, B., Sun, L., Wang, S., Li, B., Zhu, Z., & Pan, Y. (2023). Cardiovascular disease preventive effects of aspirin combined with different statins in the United States general population. Sci Rep, 13(1), 4585. https://doi.org/10.1038/s41598-023-31739-w
Magliano, D. J., Boyko, E. J., & committee, I. D. F. D. A. t. e. s. (2021). IDF Diabetes Atlas. In Idf diabetes atlas. International Diabetes Federation © International Diabetes Federation, 2021.
McInnes, I., Kaplan, I., Boy, M., Riese, R., Zuckerman, A., Clark, J., Kishore, N., Brosnan, M., Zwillich, S., & Bradley, J. (2014). AB0160 Effects of TOFACITINIB (CP-690,550) on lipid biomarkers in rat adjuvant-induced arthritis (AIA) model and in patients with active rheumatoid arthritis. Annals of the Rheumatic Diseases, 71, 646-646. https://doi.org/10.1136/annrheumdis-2012-eular.160
Moore, K. J., Sheedy, F. J., & Fisher, E. A. (2013). Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol, 13(10), 709-721. https://doi.org/10.1038/nri3520
Namitha, D., Nusrath, A., Asha Rani, N., Dhananjaya, S. Y., Lokanathan, T. H., Kruthi, B. N., & Vijay Kumar, A. G. (2022). Role of Lipid Indices in the Assessment of Microvascular Risk in Type 2 Diabetic Retinopathy Patients. Cureus, 14(3), e23395. https://doi.org/10.7759/cureus.23395
Ormazabal, V., Nair, S., Elfeky, O., Aguayo, C., Salomon, C., & Zuñiga, F. A. (2018). Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol, 17(1), 122. https://doi.org/10.1186/s12933-018-0762-4
Pérez-Baos, S., Barrasa, J. I., Gratal, P., Larrañaga-Vera, A., Prieto-Potin, I., Herrero-Beaumont, G., & Largo, R. (2017). Tofacitinib restores the inhibition of reverse cholesterol transport induced by inflammation: understanding the lipid paradox associated with rheumatoid arthritis. Br J Pharmacol, 174(18), 3018-3031. https://doi.org/10.1111/bph.13932
Singh, V. P., Bali, A., Singh, N., & Jaggi, A. S. (2014). Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol, 18(1), 1-14. https://doi.org/10.4196/kjpp.2014.18.1.1
Sun, H., Saeedi, P., Karuranga, S., Pinkepank, M., Ogurtsova, K., Duncan, B. B., Stein, C., Basit, A., Chan, J. C., & Mbanya, J. C. (2022). IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes research and clinical practice, 183, 109119.
Sundaram, M., & Yao, Z. (2010). Recent progress in understanding protein and lipid factors affecting hepatic VLDL assembly and secretion. Nutrition & Metabolism, 7(1), 35. https://doi.org/10.1186/1743-7075-7-35
Velikova, T. V., Kabakchieva, P. P., Assyov, Y. S., & Georgiev, T. А. (2021). Targeting Inflammatory Cytokines to Improve Type 2 Diabetes Control. BioMed Research International, 2021(1), 7297419. https://doi.org/https://doi.org/10.1155/2021/7297419
Viñals, M., Bermúdez, I., Llaverias, G., Alegret, M., Sanchez, R. M., Vázquez-Carrera, M., & Laguna, J. C. (2005). Aspirin increases CD36, SR-BI, and ABCA1 expression in human THP-1 macrophages. Cardiovascular Research, 66(1), 141-149. https://doi.org/10.1016/j.cardiores.2004.12.024
Vos, T., Lim, S. S., Abbafati, C., Abbas, K. M., Abbasi, M., Abbasifard, M., Abbasi-Kangevari, M., Abbastabar, H., Abd-Allah, F., & Abdelalim, A. (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet, 396(10258), 1204-1222.
Wolk, R., Armstrong, E. J., Hansen, P. R., Thiers, B., Lan, S., Tallman, A. M., Kaur, M., & Tatulych, S. (2017). Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis. Journal of Clinical Lipidology, 11(5), 1243-1256. https://doi.org/https://doi.org/10.1016/j.jacl.2017.06.012
Xie, W., Xiao, S., Huang, Y., Sun, X., & Zhang, Z. (2019). Effect of tofacitinib on cardiovascular events and all-cause mortality in patients with immune-mediated inflammatory diseases: a systematic review and meta-analysis of randomized controlled trials. Ther Adv Musculoskelet Dis, 11, 1759720x19895492. https://doi.org/10.1177/1759720x19895492
Zhang, D., Wei, Y., Huang, Q., Chen, Y., Zeng, K., Yang, W., Chen, J., & Chen, J. (2022). Important Hormones Regulating Lipid Metabolism. Molecules, 27(20), 7052. https://www.mdpi.com/1420-3049/27/20/7052
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