Serotonin receptor subtype-2B signaling is associated with interleukin-18-induced cardiomyoblast hypertrophy in vitro-Reference-Cited by-同舟云学术

Serotonin receptor subtype-2B signaling is associated with interleukin-18-induced cardiomyoblast hypertrophy in vitro

Published:2022-04-01 Issue:2 Volume:16 Page:79-87
ISSN:1875-855X
Container-title:Asian Biomedicine
language:en
Short-container-title:

Author:

Chen Chao-Yi¹²^ORCID,Leu Jyh-Gang³⁴^ORCID,Lin Kuan-Yu²^ORCID,Shih Chin-Yu¹^ORCID,Liang Yao-Jen¹²^ORCID

Affiliation:

1. Graduate Institute of Applied Science and Engineering , Fu-Jen Catholic University , New Taipei City , Taiwan

2. Department and Institute of Life Science , Fu-Jen Catholic University , New Taipei City , Taiwan

3. Fu-Jen Catholic University School of Medicine , New Taipei City , Taiwan

4. Division of Nephrology, Department of Internal Medicine , Shin Kong Wu Ho-Su Memorial Hospital , Taipei , Taiwan

Abstract

Abstract Background In patients with heart failure, interleukin-18 (IL-18) levels increase in the circulatory system and injured myocardial tissue. Serotonin (5-hydroxytryptamine) receptors subtype 2B (HTR2B) play an essential role in cardiac function and development, and their overexpression in rats leads to myocardial hypertrophy. Epigallocatechin gallate (EGCG) is cardioprotective in myocardial ischemia–reperfusion injury in rats and can prevent pressure overload-mediated cardiac hypertrophy in vivo. Mice deficient in peroxisome proliferator-activated receptor delta (PPARδ) can have cardiac dysfunction, myocardial hypertrophy, and heart failure. Matrix metalloproteinases (MMPs) are possibly involved in cardiac remodeling. However, the relationship between IL-18 signaling, cardiac hypertrophy, and the molecular mechanisms involved remain to be fully elucidated. Objectives To elucidate the relationship between HTR2B and IL-18-induced myocardial hypertrophy and examine the antihypertrophic effects of EGCG and PPARδ. Methods We induced H9c2 cardiomyoblast hypertrophy with IL-18 in vitro and investigated the downstream signaling by real-time polymerase chain reaction (PCR) and western blotting. Hypertrophy was assessed by flow cytometry. We determined the effects of EGCG and PPARδ on IL-18-induced hypertrophic signaling via HTR2B-dependent mechanisms. Results IL-18-induced H9c2 hypertrophy upregulated brain natriuretic peptide (BNP) protein and mRNA expression by inducing the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the hypertrophy was attenuated by pretreatment with EGCG (20 μM) and L-165,041 (2 μM), a PPARδ agonist. IL-18 upregulated the expression of HTR2B, which was inhibited by pretreatment with EGCG and L-165,041. SB215505 (0.1 μM), a HTR2B antagonist and siRNA for HTR2B, attenuated H9c2 hypertrophy significantly. Inhibition of HTR2B also downregulated the expression of MMP-3 and MMP-9. Conclusions IL-18 and HTR2B play critical roles in cardiomyoblast hypertrophy. EGCG and L-165,041 inhibit the expression of HTR2B and augment remodeling of H9c2 cardiomyoblasts, possibly mediated by MMP-3 and MMP-9.

Publisher

Walter de Gruyter GmbH

Link

https://www.sciendo.com/pdf/10.2478/abm-2022-0010

Reference30 articles.

1. Stroumpoulis KI, Pantazopoulos IN, Xanthos TT. Hypertrophic cardiomyopathy and sudden cardiac death. World J Cardiol. 2010; 2:289–98.

2. Li J, Umar S, Amjedi M, Iorga A, Sharma S, Nadadur RD, et al. New frontiers in heart hypertrophy during pregnancy. Am J Cardiovasc Dis. 2012; 2:192–207.

3. O’Brien LC, Mezzaroma E, Van Tassell BW, Marchetti C, Carbone S, Abbate A, Toldo S. Interleukin-18 as a therapeutic target in acute myocardial infarction and heart failure. Mol Med. 2014; 20:221–9.

4. Wang M, Markel TA, Meldrum DR. Interleukin 18 in the heart. Shock. 2008; 30:3–10.

5. Hartford M, Wiklund O, Hultén LM, Persson A, Karlsson T, Herlitz J, et al. Interleukin-18 as a predictor of future events in patients with acute coronary syndromes. Arterioscler Thromb Vasc Biol. 2010; 30:2039–46.