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Inhibition of the STIM1/Orai1 Signaling Pathway by Glycine Betaine Mitigates Myocardial Hypertrophy in Spontaneous Hypertension Rats

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Journal Cardiol Res
Date 2024 Jan 8
PMID 38187515
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Abstract

Background: Spontaneous hypertension is a leading risk factor for cardiovascular diseases morbidity and mortality. Glycine betaine (GB) is a natural vitamin that has the potential to lower blood pressure. This work attempted to investigate the role and mechanisms of GB in spontaneous hypertension.

Methods: Spontaneously hypertensive rats (SHRs) were administrated with 100, 200, or 400 mg/kg of GB by gavage or combined with by injection of lentivirus-mediated STIM1 overexpression vector. The heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart weight/body weight (HW/BW) of rats were monitored. The pathological changes in myocardium were examined by hematoxylin and eosin staining and Masson staining. The expression of genes and proteins was detected by quantitative real-time PCR, western blotting, and immunohistochemistry.

Results: GB at 200 and 400 mg/kg reduced the HR, SBP, DBP and HW/BW in SHRs. GB decreased the cross-sectional area and fibrotic area in the myocardium and downregulated the expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC) in the myocardium of SHRs. It indicated that GB treatment effectively alleviated myocardial hypertrophy in SHRs. Additionally, GB treatment repressed the expression of stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1) in the myocardium of SHRs. STIM1 overexpression reversed GB treatment-mediated inhibition of myocardial hypertrophy in SHRs.

Conclusions: In conclusion, GB repressed STIM1/Orai1 signaling pathway, which contributed to alleviating myocardial hypertrophy in SHRs. Thus, our study provides a theoretical basis for GB as an antihypertensive drug.

References
1.
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

2.
Schwab U, Torronen A, Toppinen L, Alfthan G, Saarinen M, Aro A . Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am J Clin Nutr. 2002; 76(5):961-7. DOI: 10.1093/ajcn/76.5.961. View

3.
Zou H, Chen N, Shi M, Xian M, Song Y, Liu J . The metabolism and biotechnological application of betaine in microorganism. Appl Microbiol Biotechnol. 2016; 100(9):3865-76. DOI: 10.1007/s00253-016-7462-3. View

4.
Arumugam M, Paal M, Donohue Jr T, Ganesan M, Osna N, Kharbanda K . Beneficial Effects of Betaine: A Comprehensive Review. Biology (Basel). 2021; 10(6). PMC: 8224793. DOI: 10.3390/biology10060456. View

5.
Harisa G . Oxidative stress and paraoxonase activity in experimental selenosis: effects of betaine administration. Biol Trace Elem Res. 2013; 152(2):258-66. DOI: 10.1007/s12011-013-9618-7. View