Novel Protective Role of Myeloid Differentiation 1 in Pathological Cardiac Remodelling

Xiong, Xiaoming; Liu, Yü; Yang, Minghui; Peng, Jianye; Wang, Zhiqiang; Kong, Bin; Zhong, Peng; Xiong, Liang; Quan, Dajun; Li, Qi; Wang, Guangji; Huang, He

doi:10.1038/srep41857

Cited by 27 publications

(61 citation statements)

References 48 publications

(57 reference statements)

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“…In addition, previous researchers have reported that myeloid differentiation 1 attenuated the Ang II‐induced hypertrophy in neonatal rat cardiomyocytes. Xiong et al also showed that the MEK(mitogen‐activated protein kinase kinase)‐ERK 1/2 signalling pathway was involved in the antihypertrophic effect under Ang‐II stimuli . These results are consistent with our findings.…”

Section: Discussionsupporting

confidence: 93%

Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch

Cheng¹,

Wang³

et al. 2018

J Cellular Molecular Medi

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MURC (muscle‐restricted coiled‐coil protein) is a hypertrophy‐related gene. Hypertrophy can be induced by mechanical stress. The purpose of this research was to investigate the hypothesis that MURC mediates hypertrophy in cardiomyocytes under mechanical stress. We used the in vivo model of an aortocaval shunt (AV shunt) in adult Wistar rats to induce myocardial hypertrophy. We also used the in vitro model of cyclic stretch in rat neonatal cardiomyocytes to clarify MURC expression and the molecular regulation mechanism. The flexible membrane culture plate seeding with cardiomyocytes Cardiomyocytes seeded on a flexible membrane culture plate were stretched by vacuum pressure to 20% of maximum elongation at 60 cycles/min. AV shunt induction enhanced MURC protein expression in the left ventricular myocardium. Treatment with atorvastatin inhibited the hypertrophy induced by the AV shunt. Cyclic stretch markedly enhanced MURC protein and mRNA expression in cardiomyocytes. Addition of extracellular‐signal‐regulated kinase (ERK) inhibitor PD98059, ERK small interfering RNA (siRNA), angiotensin II (Ang II) antibody and atorvastatin before stretch, abolished the induction of MURC protein. An electrophoretic mobility shift assay showed that stretch enhanced the DNA binding activity of serum response factor. Stretch increased but MURC mutant plasmid, ERK siRNA, Ang II antibody and atorvastatin reversed the transcriptional activity of MURC induced by stretch. Adding Ang II to the cardiomyocytes also induced MURC protein expression. MURC siRNA and atorvastatin inhibited the hypertrophic marker and protein synthesis induced by stretch. Treatment with atorvastatin reversed MURC expression and hypertrophy under volume overload and cyclic stretch.

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Section: Discussionsupporting

confidence: 93%

Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch

Cheng¹,

Wang³

et al. 2018

J Cellular Molecular Medi

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“…Recent evidences suggested that RP105 attenuates ischaemia/reperfusion‐induced myocardial injury via suppressing the activation of the TLR4/NF‐κB signalling pathway . Our research term also have proved that MD1 negatively regulated MEK‐ERK1/2 and NF‐κB signalling pathways and rescued the adverse effects on pressure‐overload induced cardiac remodelling . Thus, we also check the activities of MAPK and NF‐κB signalling in our study.…”

Section: Discussionsupporting

confidence: 65%

“…Another study found that MD1 deficiency played an important role in accelerating the development of inflammatory atrial fibrosis and increasing vulnerability to AF in mice with HFD‐fed induced obesity . In our previous research, we have verified MD‐1 is a vital modulator of cardiac hypertrophy and fibrosis . Thus, we hypothesized that MD‐1 may also play vital effects in obesity‐induced cardiomyopathy.…”

Section: Introductionmentioning

confidence: 79%

“…35,36 Our research term also have proved that MD1 negatively regulated MEK-ERK1/2 and NF-κB signalling pathways and rescued the adverse effects on pressure-overload induced cardiac remodelling. 21 Thus, we also check the activities of MAPK and NF-κB signalling in our study. Results suggested that high-fat stimulation promoted MEK-ERK1/2, JNK1/2, p38 and NF-κB p65 proteins phosphorylation; nevertheless, overexpression of MD-1 conversely inhibited the activation of these proteins of MAPK and NF-κB signalling pathways and alleviated cardiac remodelling, form a negative feedback loop.…”

Section: Discussionmentioning

confidence: 97%

“…11,15,18,29 Recently, our group researchers have shown that MD-1 was also highly expressed in human hearts and it attenuated pressure overload-induced cardiac fibrosis and hypertrophy through inhibiting MEK-ERK1/2 and NF-κB signalling. 21 Moreover, loss of MD-1 exacerbates the pressure overload-induced left ventricular structural and electrical remodelling through hyperactivation of CaMKII signalling and destruction of intracellular Ca 2+ homeostasis. 30 Unlike adipose tissue inflammation induced by high-fat diet in other papers, 14,15 here we demonstrated that long-term high-fat stimulated to reduce of MD-1 expression in cardiomyocytes in vitro and in vivo, and silencing of MD-1 exacerbated high-fat stimulation induced cardiac dysfunction through increasing fibrosis, while overexpression of MD-1 significantly alleviated these effects of high-fat stimulation, suggesting that MD-1 was benefit to protect myocardial function against high-fat damage.…”

Section: Discussionmentioning

confidence: 99%

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Myeloid differentiation protein 1 protected myocardial function against high‐fat stimulation induced pathological remodelling

Shen

Kong

Shuai

et al. 2019

J Cellular Molecular Medi

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Myeloid differentiation 1 (MD‐1) is a secreted protein that regulates the immune response of B cell through interacting with radioprotective 105 (RP105). Disrupted immune response may contribute to the development of cardiac diseases, while the roles of MD‐1 remain elusive. Our studies aimed to explore the functions and molecular mechanisms of MD‐1 in obesity‐induced cardiomyopathy. H9C2 myocardial cells were treated with free fatty acid (FFA) containing palmitic acid and oleic acid to challenge high‐fat stimulation and adenoviruses harbouring human MD‐1 coding sequences or shRNA for MD‐1 overexpression or knockdown in vitro. MD‐1 overexpression or knockdown transgenic mice were generated to assess the effects of MD‐1 on high‐fat diet (HD) induced cardiomyopathy in vivo. Our results showed that MD‐1 was down‐regulated in H9C2 cells exposed to FFA stimulation for 48 hours and in obesity mice induced by HD for 20 weeks. Both in vivo and in vitro , silencing of MD‐1 accelerated myocardial function injury induced by HD stimulation through increased cardiac hypertrophy and fibrosis, while overexpression of MD‐1 alleviated the effects of HD by inhibiting the process of cardiac remodelling. Moreover, the MAPK and NF‐κB pathways were overactivated in MD‐1 deficient mice and H9C2 cells after high‐fat treatment. Inhibition of MAPK and NF‐κB pathways played a cardioprotective role against the adverse effects of MD‐1 silencing on high‐fat stimulation induced pathological remodelling. In conclusion, MD‐1 protected myocardial function against high‐fat stimulation induced cardiac pathological remodelling through negative regulation for MAPK/NF‐κB signalling pathways, providing feasible strategies for obesity cardiomyopathy.

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The Akt pathway mediates the protective effects of myeloid differentiation protein 1 in pathological cardiac remodelling

et al. 2021

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Aims Myeloid differentiation protein 1 (MD1) was shown to ameliorate pressure overload-induced cardiac hypertrophy and fibrosis by negatively regulating the MEK-ERK1/2 and NF-κB pathways. However, whether MD1 modulates cardiac function and whether the Akt pathway mediates the benefits of MD1 in pressure overload-induced cardiac remodelling remain unclear. Methods and Results Male cardiac-specific transgenic MD1 (MD1-TG) mice, MD1-knockout (KO) mice and wild-type (WT) littermates aged 8-10 weeks were subjected to sham operation and aortic banding (AB) for 4 weeks. Then, left ventricular (LV) hypertrophy, fibrosis and function of the mice were assessed. When compared with WT-AB mice, MD1-TGs showed decreased cross-sectional area (CSA) of cardiomyocytes (P < 0.001), mRNA expression of β-myosin heavy chain (β-MHC) (P < 0.02), ratios of heart weight/body weight and heart weight/tibia length (P < 0.04) and collagen volume fraction (P < 0.001). The LV end-diastolic diameter was reduced, and LV ejection fraction and fractional shortening were improved in MD1-TG-AB mice than in WT-AB mice (P < 0.05). In cultured H9C2 cells, adenovirus vector-mediated MD1 overexpression decreased angiotensin II-induced mRNA expression of brain natriuretic peptide (BNP) and β-MHC and cell CSA (P < 0.002), whereas knockdown of MD1 by shRNA exhibited opposite effects (P < 0.04). Mechanistically, MD1 suppressed pathological cardiac remodelling at least partly by blocking Akt pathway. Akt inactivation by MK2206 largely offset the pro-hypertrophic effects of MD1 deficiency in angiotensin II-stimulated cardiomyocytes. Conclusions The Akt pathway mediates the protective effects of MD1 in pressure overload-induced cardiac remodelling in mice. Targeting MD1 may provide therapeutic strategy for the treatment of pathological cardiac remodelling and heart failure.

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Novel Protective Role of Myeloid Differentiation 1 in Pathological Cardiac Remodelling

Cited by 27 publications

References 48 publications

Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch

Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch

Myeloid differentiation protein 1 protected myocardial function against high‐fat stimulation induced pathological remodelling

The Akt pathway mediates the protective effects of myeloid differentiation protein 1 in pathological cardiac remodelling

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