Toll-like receptors in cardiac hypertrophy

Zhang, Yanan; Wu, Jimin; Dong, Erdan; Wang, Zhanli; Xiao, Han

doi:10.3389/fcvm.2023.1143583

Cited by 3 publications

(1 citation statement)

References 165 publications

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“…[ 35 ] Toll-like receptors, as key factors that regulate innate immune responses, can lead to acute and chronic inflammation. [ 36 ] Inflammation is a characteristic feature of cardiac hypertrophy and mediates the important roles of toll-like receptors in the HCM process. Further interventions using molecules involved in these pathways might be of great significance in improving the development of HCM.…”

Section: Discussionmentioning

confidence: 99%

Roles of the crucial mitochondrial DNA in hypertrophic cardiomyopathy prognosis and diagnosis: A review

Liao,

Zhou,

Zeng

et al. 2023

Medicine

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Mitochondrial DNA is implicated in hypertrophic cardiomyopathy (HCM) development. We aimed to identify valuable mtDNAs that contribute to the development of HCM. Differentially expressed mitochondrial DNAs (DEMGs) between HCM and controls were screened. GO and KEGG functional enrichment analyses were performed, and the optimum genes were explored using the LASSO regression mode and SVM-RFE model. A diagnostic scoring model was constructed and verified using ROC curves. Mitochondria-based subtypes were identified. Immune performance among the subtypes including immune cells, immune checkpoint genes, and HLA family genes was analyzed. Finally, an mRNA-transcription factor (TF)-miRNA network was constructed using Cytoscape software. Twelve DEMGs in HCM were selected. Among them, 6 DEMGs, including PDK4, MGST1, TOMM40, LYPLAL1, GATM, and CPT1B were demonstrated as DEMGs at the point of intersection of Lasso regression and SVM-RFE. The ROC of the model for the training and validation datasets was 0.999 and 0.958, respectively. Two clusters were divided, and 4 immune cell types were significantly different between the 2 clusters, including resting mast cells, macrophages M2, and plasma cells. Nine upregulated KEGG pathways were enriched in cluster 1 vs. cluster 2 including O-glycan biosynthesis, the ErbB signaling pathway, and the GnRH signaling pathway. Meanwhile, 49 down-regulated pathways were enriched such as the toll-like signaling pathway and natural killer cell-mediated cytotoxicity pathway. The 6 gene-based mRNA-TF-miRNA networks included other 133 TFs and 18 miRNAs. Six DEMGs in HCM, including PDK4, MGST1, TOMM40, LYPLAL1, GATM, and CPT1B, can be indicative of HCM prognosis or disease progression.

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Section: Discussionmentioning

confidence: 99%

Roles of the crucial mitochondrial DNA in hypertrophic cardiomyopathy prognosis and diagnosis: A review

Liao,

Zhou,

Zeng

et al. 2023

Medicine

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Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury

Wang,

Xu,

Yan

et al. 2024

Biomedicines

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Ischemia reperfusion (I/R) is a common pathological process which occurs mostly in organs like the heart, brain, kidney, and lung. The injury caused by I/R gradually becomes one of the main causes of fatal diseases, which is an urgent clinical problem to be solved. Although great progress has been made in therapeutic methods, including surgical, drug, gene therapy, and transplant therapy for I/R injury, the development of effective methods to cure the injury remains a worldwide challenge. In recent years, exosomes have attracted much attention for their important roles in immune response, antigen presentation, cell migration, cell differentiation, and tumor invasion. Meanwhile, exosomes have been shown to have great potential in the treatment of I/R injury in organs. The study of the exosome-mediated signaling pathway can not only help to reveal the mechanism behind exosomes promoting reperfusion injury recovery, but also provide a theoretical basis for the clinical application of exosomes. Here, we review the research progress in utilizing various exosomes from different cell types to promote the healing of I/R injury, focusing on the classical signaling pathways such as PI3K/Akt, NF-κB, Nrf2, PTEN, Wnt, MAPK, toll-like receptor, and AMPK. The results suggest that exosomes regulate these signaling pathways to reduce oxidative stress, regulate immune responses, decrease the expression of inflammatory cytokines, and promote tissue repair, making exosomes a competitive emerging vector for treating I/R damage in organs.

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Toll-like Receptor 4 Differentially Modulates Cardiac Function in Response to Chronic Exposure to High-Fat Diet and Pressure Overload

Tian,

Jarrah,

Herz

et al. 2023

Nutrients

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Background/Aim: The impact of myocardial stressors such as high-fat diet (HFD) and pressure overload has been extensively studied. Toll-like receptor 4 (TLR4) deficiency has been suggested to have a protective role in response to these stressors, although some conflicting data exist. Furthermore, there is limited information about the role of TLR4 on cardiac remodeling in response to long-term exposure to stressors. This study aims to investigate the effects of TLR4 deficiency on cardiac histology and physiology in response to chronic stressors. Methods: TLR4-deficient (TLR4−/−) and wild-type (WT) mice were subjected to either HFD or a normal diet (ND) for 28 weeks. Another group underwent abdominal aortic constriction (AAC) or a sham procedure and was monitored for 12 weeks. Inflammatory markers, histology, and echocardiography were used to assess the effects of these interventions. Results: TLR4−/− mice exhibited reduced cardiac hypertrophy and fibrosis after long-term HFD exposure compared to ND without affecting cardiac function. On the other hand, TLR4 deficiency worsened cardiac function in response to AAC, leading to decreased ejection fraction (EF%) and increased end-systolic volume (ESV). Conclusions: TLR4 deficiency provided protection against HFD-induced myocardial inflammation but impaired hemodynamic cardiac function under pressure overload conditions. These findings highlight the crucial role of TLR4 and its downstream signaling pathway in maintaining cardiac output during physiologic cardiac hypertrophy in response to pressure overload.

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Toll-like receptors in cardiac hypertrophy

Cited by 3 publications

References 165 publications

Roles of the crucial mitochondrial DNA in hypertrophic cardiomyopathy prognosis and diagnosis: A review

Roles of the crucial mitochondrial DNA in hypertrophic cardiomyopathy prognosis and diagnosis: A review

Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury

Toll-like Receptor 4 Differentially Modulates Cardiac Function in Response to Chronic Exposure to High-Fat Diet and Pressure Overload

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