Activation of Toll‐like receptor 7 provides cardioprotection in septic cardiomyopathy‐induced systolic dysfunction

Xie, Sai‐Sai; Wu, Qin; Xu, Man; Chen, Liu; Zhang, Min; Xing, Yun; Shi, Wenke; Wu, Hongyan; Zeng, Xiaofeng; Chen, Si; Guo, Haipeng; Deng, Wen-feng; Tang, Qi‐Zhu

doi:10.1002/ctm2.266

Cited by 23 publications

(13 citation statements)

References 58 publications

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“…For example, it is well known that TLR4 and TLR2 play an important role in mediating the development in sepsis-induced myocardial injury ( Spiller et al, 2008 ; Alves-Filho et al, 2009 ; Zou et al, 2010 ). On the contrary, TLR7 upregulates cAMP/PKA/PLN signaling and improves septic cardiomyopathy in LPS-treated mice ( Saiyang et al, 2021 ). In addition to the classic TLRs/MyD88/NF-κB pathway, STING/IRF3/NLRP3 signaling is involved in the LPS-induced cardiac inflammation, apoptosis, and dysfunction ( Li N. et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Time Series Transcriptomic Analysis by RNA Sequencing Reveals a Key Role of PI3K in Sepsis-Induced Myocardial Injury in Mice

et al. 2022

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Septic cardiomyopathy is the main complication and cause of death of severe sepsis with limited therapeutic strategy. However, the molecular mechanism of sepsis-induced cardiac injury remains unclear. The present study was designed to investigate differentially expressed genes (DEGs) involved in the pathogenesis of septic cardiomyopathy induced by cecal ligation and puncture (CLP) in mice. Male C57BL/6J mice (8–10 weeks old) were subjected to CLP with 21-gauge needles for 24, 48, and 72 h. Myocardial function was assessed by echocardiography. The pathological changes of the heart were evaluated by hematoxylin and eosin as well as immunohistochemical staining. Time series RNA sequencing was utilized to investigate the gene expression profiles. CLP surgery resulted in a significant decrease of animal survival rate and left ventricle contractile function, and an increase in cardiac dilation and infiltration of proinflammatory cells including Mac-2+ macrophages in a time-dependent manner. RNA sequencing identified 5,607 DEGs in septic myocardium at 24, 48, and 72 h after CLP operation. Moreover, gene ontology analysis revealed that these DEGs were mainly associated with the biological processes, including cell adhesion, immune system process, inflammatory response, and positive regulation of cell migration. KEGG pathway enrichment analysis indicated that Staphylococcus aureus infection, osteoclast differentiation, leishmaniasis, and ECM-receptor interaction were significantly altered in septic hearts. Notably, Pik3r1 and Pik3r5 were localized in the center of the gene co-expression network, and were markedly upregulated in CLP-induced septic myocardium. Further, blocking PI3Kγ by the specific inhibitor CZC24832 significantly protected against sepsis-induced cardiac impairment. The present study uncovers the gene expression signatures of CLP-induced myocardial injury and sheds light on the role of Pik3r5 in septic cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

Time Series Transcriptomic Analysis by RNA Sequencing Reveals a Key Role of PI3K in Sepsis-Induced Myocardial Injury in Mice

et al. 2022

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“…Cardiac fibroblasts (CFs) were isolated from adult mice by enzymatic digestion and cultured in a DMEM medium, as previously described 26 . CFs in HR group were treated with hypoxia for 24 h and reoxygenation for 6 h with 5% CO 2 , 94% N 2, and 1% O 2 at 37 °C in tri-gas incubators for 48 h. CFs were infected with Ad-LacZ or Ad-HSP47-GFP for 24 h and treated with HR or normoxia for another 48 h. CFs were pretreated with HSP47 inhibitor (Col003, 50 μmol/L) or DMSO for 48 h in the absence or presence of normoxia.…”

Section: Methodsmentioning

confidence: 99%

“…As previously described, cells were lysed with RIPA lysis buffer (Sevicebio, China) and protease inhibitors 26 . The protein concentration was measured with a BCA protein determination kit (Thermo Scientific, 23225).…”

Section: Methodsmentioning

confidence: 99%

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Cardiac fibroblast heat shock protein 47 aggravates cardiac fibrosis post myocardial ischemia–reperfusion injury by encouraging ubiquitin specific peptidase 10 dependent Smad4 deubiquitination

Xie

Xing

Shi

et al. 2022

Acta Pharmaceutica Sinica B

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“…Because sepsis is an inflammatory condition, inflammatory cytokine production is seen to some extent in all affected organs, including the heart ( 144 ). LPS (lipopolysaccharide) administration in vivo can induce a model of septic cardiomyopathy ( 145 ). Global Mst1 deletion can attenuate LPS-mediated upregulation of TNFα and IL6 levels in the heart, thereby improving cardiac function ( 131 ).…”

Section: The Hippo-yap Pathway and The Inflammatory Response During H...mentioning

confidence: 99%

The Hippo-YAP pathway in various cardiovascular diseases: Focusing on the inflammatory response

2022

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The Hippo pathway was initially discovered in Drosophila melanogaster and mammals as a key regulator of tissue growth both in physiological and pathological states. Numerous studies depict the vital role of the Hippo pathway in cardiovascular development, heart regeneration, organ size and vascular remodeling through the regulation of YAP (yes-associated protein) translocation. Recently, an increasing number of studies have focused on the Hippo-YAP pathway in inflammation and immunology. Although the Hippo-YAP pathway has been revealed to play controversial roles in different contexts and cell types in the cardiovascular system, the mechanisms regulating tissue inflammation and the immune response remain to be clarified. In this review, we summarize findings from the past decade on the function and mechanism of the Hippo-YAP pathway in CVDs (cardiovascular diseases) such as myocardial infarction, cardiomyopathy and atherosclerosis. In particular, we emphasize the role of the Hippo-YAP pathway in regulating inflammatory cell infiltration and inflammatory cytokine activation.

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Activation of Toll‐like receptor 7 provides cardioprotection in septic cardiomyopathy‐induced systolic dysfunction

Cited by 23 publications

References 58 publications

Time Series Transcriptomic Analysis by RNA Sequencing Reveals a Key Role of PI3K in Sepsis-Induced Myocardial Injury in Mice

Time Series Transcriptomic Analysis by RNA Sequencing Reveals a Key Role of PI3K in Sepsis-Induced Myocardial Injury in Mice

Cardiac fibroblast heat shock protein 47 aggravates cardiac fibrosis post myocardial ischemia–reperfusion injury by encouraging ubiquitin specific peptidase 10 dependent Smad4 deubiquitination

The Hippo-YAP pathway in various cardiovascular diseases: Focusing on the inflammatory response

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