Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats Via Inhibiting Inflammatory Response

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2018 Jun 5

PMID 29861433

Citations 19

Authors

Jia-Mei Yang

Ru Zhou

Min Zhang

Huan-Ran Tan

Jian-Qiang Yu

Affiliations

Soon will be listed here.

Abstract

Background: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. To test our hypothesis, we aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms.

Methods: PAH was induced by monocrotaline (50 mg/kg) and oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricle hypertrophy index were used to evaluate the development of PAH. Hematoxylin and eosin staining and Masson staining were performed to measure the extents of vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by immunohistochemical staining. Nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were assessed by Western blot.

Results: This study showed that betaine improved the abnormalities in right ventricular systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy index, and pulmonary arterial remodeling induced by monocrotaline compared with the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot indicated that the protein expression levels of NF-κB, TNF-α, and IL-1β significantly decreased ( < 0.01).

Conclusion: Our study demonstrated that betaine attenuated PAH through its anti-inflammatory effects. Hence, the present data may offer novel targets and promising pharmacological perspectives for treating monocrotaline-induced PAH.

Citing Articles

Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics.

Ba H, Guo Y, Jiang Y, Li Y, Dai X, Liu Y Respir Res. 2024; 25(1):221.

PMID: 38807129 PMC: 11131231. DOI: 10.1186/s12931-024-02775-5.

Forsythoside B Mitigates Monocrotaline-Induced Pulmonary Arterial Hypertension via Blocking the NF-κB Signaling Pathway to Attenuate Vascular Remodeling.

Liu J, Fang G, Lan C, Qiu C, Yao L, Zhang Q Drug Des Devel Ther. 2024; 18:767-780.

PMID: 38495631 PMC: 10942864. DOI: 10.2147/DDDT.S444605.

Comparative study of H-NMR metabolomic profile of canine synovial fluid in patients affected by four progressive stages of spontaneous osteoarthritis.

Piccionello A, Sassaroli S, Pennasilico L, Rossi G, Cerbo A, Riccio V Sci Rep. 2024; 14(1):3627.

PMID: 38351089 PMC: 10864333. DOI: 10.1038/s41598-024-54144-3.

Bioactive Components of and Deep-Processing Fermentation Products.

Qiang X, Xia T, Geng B, Zhao M, Li X, Zheng Y Molecules. 2023; 28(24).

PMID: 38138534 PMC: 10745962. DOI: 10.3390/molecules28248044.

CC chemokines Modulate Immune responses in Pulmonary Hypertension.

Yan Q, Liu S, Sun Y, Chen C, Yang Y, Yang S J Adv Res. 2023; 63:171-186.

PMID: 37926143 PMC: 11380027. DOI: 10.1016/j.jare.2023.10.015.

References

Zhou Z, Xiao J, Fan H, Yu Y, He R, Feng X . Polyphenols from wolfberry and their bioactivities. Food Chem. 2016; 214:644-654. DOI: 10.1016/j.foodchem.2016.07.105. View

Wong M, Kantores C, Ivanovska J, Jain A, Jankov R . Simvastatin prevents and reverses chronic pulmonary hypertension in newborn rats via pleiotropic inhibition of RhoA signaling. Am J Physiol Lung Cell Mol Physiol. 2016; 311(5):L985-L999. DOI: 10.1152/ajplung.00345.2016. View

Adegunsoye A, Balachandran J . Inflammatory response mechanisms exacerbating hypoxemia in coexistent pulmonary fibrosis and sleep apnea. Mediators Inflamm. 2015; 2015:510105. PMC: 4402194. DOI: 10.1155/2015/510105. View

Wang Q, Zuo X, Wang Y, Xie W, Wang H, Zhang M . Monocrotaline-induced pulmonary arterial hypertension is attenuated by TNF-α antagonists via the suppression of TNF-α expression and NF-κB pathway in rats. Vascul Pharmacol. 2012; 58(1-2):71-7. DOI: 10.1016/j.vph.2012.07.006. View

Li L, Wei C, Kim I, Janssen-Heininger Y, Gupta S . Inhibition of nuclear factor-κB in the lungs prevents monocrotaline-induced pulmonary hypertension in mice. Hypertension. 2014; 63(6):1260-9. DOI: 10.1161/HYPERTENSIONAHA.114.03220. View

Alirezaei M, Khoshdel Z, Dezfoulian O, Rashidipour M, Taghadosi V . Beneficial antioxidant properties of betaine against oxidative stress mediated by levodopa/benserazide in the brain of rats. J Physiol Sci. 2015; 65(3):243-52. PMC: 10717468. DOI: 10.1007/s12576-015-0360-0. View

Varshney R, Ali Q, Wu C, Sun Z . Monocrotaline-Induced Pulmonary Hypertension Involves Downregulation of Antiaging Protein Klotho and eNOS Activity. Hypertension. 2016; 68(5):1255-1263. PMC: 5063703. DOI: 10.1161/HYPERTENSIONAHA.116.08184. View

Xiong S, Guo R, Yang Z, Xu L, Du L, Li R . Treg depletion attenuates irradiation-induced pulmonary fibrosis by reducing fibrocyte accumulation, inducing Th17 response, and shifting IFN-γ, IL-12/IL-4, IL-5 balance. Immunobiology. 2015; 220(11):1284-91. DOI: 10.1016/j.imbio.2015.07.001. View

Cao H, Zhou X, Zhang J, Huang X, Zhai Y, Zhang X . Hydrogen sulfide protects against bleomycin-induced pulmonary fibrosis in rats by inhibiting NF-κB expression and regulating Th1/Th2 balance. Toxicol Lett. 2013; 224(3):387-94. DOI: 10.1016/j.toxlet.2013.11.008. View

10.

Lee M, Tsai K, Hsu J, Shin S, Wu J, Yeh J . Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways. Sci Rep. 2016; 6:31788. PMC: 5007506. DOI: 10.1038/srep31788. View

11.

Barst R, Beghetti M, Pulido T, Layton G, Konourina I, Zhang M . STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension. Circulation. 2014; 129(19):1914-23. DOI: 10.1161/CIRCULATIONAHA.113.005698. View

12.

Xu L, Huang D, Hu Q, Wu J, Wang Y, Feng J . Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet. Br J Nutr. 2015; 113(12):1835-43. DOI: 10.1017/S0007114515001130. View

13.

Gao H, Cheng Y, Zong L, Huang L, Qiao C, Li W . Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway. Clin Exp Hypertens. 2017; 39(1):34-41. DOI: 10.1080/10641963.2016.1210620. View

14.

Voelkel N, Tuder R, Bridges J, Arend W . Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline. Am J Respir Cell Mol Biol. 1994; 11(6):664-75. DOI: 10.1165/ajrcmb.11.6.7946395. View

15.

Li X, Wang H, Yang C, Zhang X, Han D, Wang H . Fluoxetine inhibited extracellular matrix of pulmonary artery and inflammation of lungs in monocrotaline-treated rats. Acta Pharmacol Sin. 2011; 32(2):217-22. PMC: 4085716. DOI: 10.1038/aps.2010.187. View

16.

Wang R, Jiang F, Zheng Q, Li C, Peng X, He C . Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a systematic review. Respir Med. 2014; 108(3):531-7. DOI: 10.1016/j.rmed.2014.01.003. View

17.

Go E, Jung K, Kim J, Yu B, Young Chung H . Betaine suppresses proinflammatory signaling during aging: the involvement of nuclear factor-kappaB via nuclear factor-inducing kinase/IkappaB kinase and mitogen-activated protein kinases. J Gerontol A Biol Sci Med Sci. 2005; 60(10):1252-64. DOI: 10.1093/gerona/60.10.1252. View

18.

Huertas A, Tu L, Thuillet R, Le Hiress M, Phan C, Ricard N . Leptin signalling system as a target for pulmonary arterial hypertension therapy. Eur Respir J. 2015; 45(4):1066-80. DOI: 10.1183/09031936.00193014. View

19.

Polonio I, Acencio M, Pazetti R, de Almeida F, Silva B, Pereira K . Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats. J Bras Pneumol. 2014; 40(4):421-4. PMC: 4201173. DOI: 10.1590/s1806-37132014000400010. View

20.

Feng S, Chen S, Yu W, Zhang D, Zhang C, Tang C . HS inhibits pulmonary arterial endothelial cell inflammation in rats with monocrotaline-induced pulmonary hypertension. Lab Invest. 2016; 97(3):268-278. DOI: 10.1038/labinvest.2016.129. View