Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy

Wang, Yi; Guo, Zhiheng; Gao, Yu-Hang; Liang, Ping; Shan, Yanhong; He, Jin

doi:10.1186/s13578-019-0348-1

Cited by 15 publications

(9 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, p38 MAPK inhibitor, PI3K inhibitor, and the c-JNK inhibitor didnot affect arterial blood pressure or renal sympathetic nerve activity in heart failure (Shinohara et al, 2015) (Figure 2). LCZ696, an AT1 R blocker, attenuated the hypertrophic expression of ANP, βMHC, and TIMP2 in Ang II-induced remodeling in cardiomyocyte and collagen I, collagen III, and TGF-β in cardiac fibroblasts via ERK inhibition (Wang Y. et al, 2019). A potent angiogenesis inhibitor, endostatin reduced the levels of ANP and BNP in primary neonatal rat cardiomyocytes and Ang II-treated rats via the cAMP/PKA pathway (Dai et al, 2019).…”

Section: Angiotensin II In Cardiac Remodelingmentioning

confidence: 99%

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

et al. 2021

View full text Add to dashboard Cite

The multifaceted nature of the renin-angiotensin system (RAS) makes it versatile due to its involvement in pathogenesis of the cardiovascular disease. Angiotensin II (Ang II), a multifaceted member of RAS family is known to have various potential effects. The knowledge of this peptide has immensely ameliorated after meticulous research for decades. Several studies have evidenced angiotensin I receptor (AT1 R) to mediate the majority Ang II-regulated functions in the system. Functional crosstalk between AT1 R mediated signal transduction cascades and other signaling pathways has been recognized. The review will provide an up-to-date information and recent discoveries involved in Ang II receptor signal transduction and their functional significance in the cardiovascular system for potential translation in therapeutics. Moreover, the review also focuses on the role of stem cell-based therapies in the cardiovascular system.

show abstract

Section: Angiotensin II In Cardiac Remodelingmentioning

confidence: 99%

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Phosphorylation of ERK at threonine 188, along with the activation of ERK5, has also been shown to be related to the pathological process of cardiomyocyte hypertrophy ( 41 ). Furthermore, as the first angiotensin receptor-enkephalin inhibitor, LCZ696 has been shown to attenuate cardiac remodeling by inhibiting the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy ( 52 ). Collectively, these studies suggest that the ERK1/2 signaling pathway plays a critical role in the process of cardiomyocyte hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Interactions between the ERK1/2 signaling pathway and PCAF play a key role in PE‑induced cardiomyocyte hypertrophy

Mao

Chang

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

Cardiomyocyte hypertrophy is a compensatory phase of chronic heart failure that is induced by the activation of multiple signaling pathways. The extracellular signal-regulated protein kinase (ERK) signaling pathway is an important regulator of cardiomyocyte hypertrophy. In our previous study, it was demonstrated that phenylephrine (PE)-induced cardiomyocyte hypertrophy involves the hyperacetylation of histone H3K9ac by P300/CBP-associated factor (PCAF). However, the upstream signaling pathway has yet to be fully identified. In the present study, the role of the extracellular signal-regulated protein kinase (ERK)1/2 signaling pathway in PE-induced cardiomyocyte hypertrophy was investigated. The mice cardiomyocyte hypertrophy model was successfully established by treating cells with PE in vitro. The results showed that phospho-(p-)ERK1/2 interacted with PCAF and modified the pattern of histone H3K9ac acetylation. An ERK inhibitor (U0126) and/or a histone acetylase inhibitor (anacardic acid; AA) attenuated the overexpression of phospho-ERK1/2 and H3K9ac hyperacetylation by inhibiting the expression of PCAF in PE-induced cardiomyocyte hypertrophy. Moreover, U0126 and/or AA could attenuate the overexpression of several biomarker genes related to cardiac hypertrophy (myocyte enhancer factor 2C, atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain) and prevented cardiomyocyte hypertrophy. These results revealed a novel mechanism in that AA protects against PE-induced cardiomyocyte hypertrophy in mice via the ERK1/2 signaling pathway, and by modifying the acetylation of H3K9ac. These findings may assist in the development of novel methods for preventing and treating hypertrophic cardiomyopathy.

show abstract

“…It has been reported that Mep1a activates extracellular-signalregulated kinase1/2 (ERK1/2) signaling pathway [46], which plays essential roles in Ang II-induced cardiac remodeling [47,48]. Therefore, we hypothesized that Mep1a regulated the ERK1/2 activation, which was involved in Ang II-induced cardiac hypertrophy, fibrosis and inflammation.…”

Section: Mep1a Mediated Erk1/2 Activation and Contributed To Cardiac Remodelingmentioning

confidence: 96%

Mep1a contributes to Ang II-induced cardiac remodeling by promoting cardiac hypertrophy, fibrosis and inflammation

Hou

Zhang

et al. 2021

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

Pathological cardiac remodeling, characterized by excessive deposition of extracellular matrix proteins and cardiac hypertrophy, leads to the development of heart failure. Meprin α (Mep1a), a zinc metalloprotease, previously reported to participate in the regulation of inflammatory response and fibrosis, may also contribute to cardiac remodeling, although whether and how it participates in this process remains unknown. Here, in this work, we investigated the role of Mep1a in pathological cardiac remodeling, as well as the effects of the Mep1a inhibitor actinonin on cardiac remodeling-associated phenotypes. We found that Mep1a deficiency or chemical inhibition both significantly alleviated TAC-and Ang II-induced cardiac remodeling and dysfunction. Mep1a deletion and blocking both attenuated TAC-and Ang II-induced heart enlargement and increases in the thickness of the left ventricle anterior and posterior walls, and reduced expression of pro-hypertrophic markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and myosin heavy chain beta (β-MHC). In addition, Mep1a deletion and blocking significantly inhibited TAC-and Ang II-induced cardiac fibroblast activation and production of extracellular matrix (ECM). Moreover, in Mep1a − /− mice and treatment with actinonin significantly reduced Ang II-induced infiltration of macrophages and proinflammatory cytokines. Notably, we found that in vitro, Mep1a is expressed in cardiac myocytes and fibroblasts and that Mep1a deletion or chemical inhibition both markedly suppressed Ang II-induced hypertrophy of rat or mouse cardiac myocytes and activation of rat or mouse cardiac fibroblasts. In addition, blocking Mep1a in macrophages reduced Ang II-induced expression of interleukin (IL)-6 and IL-1β, strongly suggesting that Mep1a participates in cardiac remodeling processes through regulation of inflammatory cytokine expression. Mechanism studies revealed that Mep1a mediated ERK1/2 activation in cardiac myocytes, fibroblasts and macrophages and contributed to cardiac remodeling. In light of our findings that blocking Mep1a can ameliorate cardiac remodeling via inhibition of cardiac hypertrophy, fibrosis, and inflammation, Mep1a may therefore serve as a strong potential candidate for therapeutic targeting to prevent cardiac remodeling.

show abstract

Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy

Cited by 15 publications

References 26 publications

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

Interactions between the ERK1/2 signaling pathway and PCAF play a key role in PE‑induced cardiomyocyte hypertrophy

Mep1a contributes to Ang II-induced cardiac remodeling by promoting cardiac hypertrophy, fibrosis and inflammation

Contact Info

Product

Resources

About