Effects of Proteasome Inhibitor on Catalase Expression and Intima-media Thickness in the Aorta of Atherosclerotic Rats

Ismawati Ismawati, Enikarmila Asni, Ilhami Romus, Mukhyarjon Mukhyarjon, Winarto Winarto, Muhammad Fadhillah Arif, M Derillovyandra Dwi Anugrah


Various studies have been carried out to obtain proper management for atherosclerosis. Proteasome, a subcellular enzyme complex, is a potential therapeutic target for atherosclerosis. However, the effect of proteasome inhibitors on atherosclerosis still needs to be explored. It was an experimental study with a post-test-only control group design conducted at the Faculty of Medicine, Universitas Riau in Juni–November 2021. This study aimed to analyze the effects of proteasome inhibitors on catalase expression and intima-media thickness (IMT) in the thoracic aorta of atherosclerotic rats. Fifteen male Wistar rats were randomly divided into three groups (five rats per group), namely rats given standard feed (control, group I), rats induced atherosclerosis (group II), and rats induced atherosclerosis and given proteasome inhibitor (group III). The proteasome inhibitor, bortezomib, 50 µg/kgBW/day was given intraperitoneally on days one and three. After 4 days, rats were terminated, and the thoracic aorta was taken for the IMT analysis and catalase expression assessment using immunohistochemistry. Catalase expression was carried out quantitatively using Adobe Photoshop software. Analysis of variance test was used to compare the expression of catalase and IMT. A p value<0.05 was considered statistically significant. The results showed a significant decrease in IMT in group III compared to group II and an increase in catalase expression in group III compared to group II but not statistically significant. This study concludes that administration of bortezomib 50 µg/kgBW in atherosclerotic rats could inhibit thickening tunica intima-media in the thoracic aorta, although not significantly increasing the catalase expression.


Atherosclerosis; catalase; intima-media thickness; proteasome inhibitor

Full Text:



Barquera S, Pedroza-Tobías A, Medina C, Hernández-Barrera L, Bibbins-Domingo K, Lozano R, et al. Global overview of the epidemiology of atherosclerotic cardiovascular disease. Arch Med Res. 2015;46(5):328–38.

World Health Organization. Cardiovascular diseases (CVDs) [Internet]. Geneva: World Health Organization; 2021 [cited 2021 December 10]. Available from: https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).

Wahidah W, Harahap RA. PJK (penyakit jantung koroner) vs SKA (sindrome kororner akut) prespektif epidemiologi. Afiasi. 2021;6(1):54–65.

Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol. 2019;234(10):16812–23.

Mitchell RN. Blood vessels. In: Kumar V, Abbas AK, Aster JC, editors. Robbins basic pathology. 9th Edition. Philadelphia: Saunders; 2013. p. 327–64.

Andreou I, Sun X, Stone PH, Edelman ER, Feinberg MW. miRNAs in atherosclerotic plaque initiation, progression, and rupture. Trends Mol Med. 2015;21(5):307–18.

Nezu T, Hosomi N, Aoki S, Matsumoto M. Carotid intima-media thickness for atherosclerosis. J Atheroscler Thromb. 2016;23(1):18–31.

Wilck N, Ludwig A. Targeting the ubiquitin-proteasome system in atherosclerosis: status quo, challenges, and perspectives. Antioxid Redox Signal. 2014;21(17):2344–63.

Ismawati, Oenzil F, Yanwirasti, Yerizel E. Changes in expression of proteasome in rats at different stages of atherosclerosis. Anat Cell Biol. 2016;49(2):99–106.

Nunes AT, Annunziata CM. Proteasome inhibitors: structure and function. Semin Oncol. 2017;44(6):377–80.

Wilck N, Fechner M, Dreger H, Hewing B, Arias A, Meiners S, et al. Attenuation of early atherogenesis in low-density lipoprotein receptor-deficient mice by proteasome inhibition. Arterioscler Thromb Vasc Biol. 2012;32(6):1418–26.

Wilck N, Fechner M, Dan C, Stangl V, Stangl K, Ludwig A. The effect of low-dose proteasome inhibition on pre-existing atherosclerosis in LDL receptor-deficient mice. Int J Mol Sci. 2017;18(4):781.

Ludwig A, Fechner M, Wilck N, Meiners S, Grimbo N, Baumann G, et al. Potent anti-inflammatory effects of low-dose proteasome inhibition in the vascular system. J Mol Med (Berl). 2009;87(8):793–802.

Li S, Wang X, Li Y, Kost CK Jr, Martin DS. Bortezomib, a proteasome inhibitor, attenuates angiotensin II-induced hypertension and aortic remodeling in rats. PLoS One. 2013;8(10):e78564.

Barry H, Gutteridge JMC. Free radicals in biology and medicine. 5th Edition. Oxford: Oxford University Press; 2015.

Glorieux C, Zamocky M, Sandoval JM, Verrax J, Calderon PB. Regulation of catalase expression in healthy and cancerous cells. Free Radic Biol Med. 2015;87:84–97.

Al-Joufi F, Al-Ani IM, Saxena AK, Talib NA, Mokhtar RH, Ku-Zaifah N. Assessment of anti-atherosclerotic effect of Eurycoma longifolia extract on high-fat diet model in rats. I: histological study. Eur J Anat. 2016;20(2):131–6.

Lehr HA, Mankoff DA, Corwin D, Santeusanio G, Gown AM. Application of photoshop-based image analysis to quantification of hormone receptor expression in breast cancer. J Histochem Cytochem. 1997;45(11):1559–65.

Kattoor AJ, Pothineni NVK, Palagiri D, Mehta JL. Oxidative stress in atherosclerosis. Curr Atheroscler Rep. 2017;19(11):42.

Navia-Pelaez JM, Campos-Mota GP, Araujo de Souza JC, Aguilar EC, Stergiopulos N, Alvarez-Leite JI, et al. nNOS uncoupling by oxidized LDL: implications in atherosclerosis. Free Radic Biol Med. 2017;113:335–46.

Negre-Salvayre A, Guerby P, Gayral S, Laffargue M, Salvayre R. Role of reactive oxygen species in atherosclerosis: lessons from murine genetic models. Free Radic Biol Med. 2020;149:8–22.

Bastani A, Rajabi S, Daliran A, Saadat H, Karimi-busheri F. Oxidant and antioxidant status in coronary artery disease. Biomed Rep. 2018;9(4):327–32.

Dreger H, Westphal K, Weller A, Baumann G, Stangl V, Meiners S, et al. Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection. Cardiovasc Res. 2009;83(2):354–61.

DOI: https://doi.org/10.29313/gmhc.v10i3.9508

pISSN 2301-9123 | eISSN 2460-5441

Visitor since 19 October 2016: 

View My Stats

Free counters!

Global Medical and Health Communication is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.