H2S attenuates the myocardial fibrosis in diabetic rats through modulating PKC-ERK1/2MAPK signaling pathway

Meng

et al. 2020

Exp Biol Med (Maywood)

Smoking has become a major cause of chronic obstructive pulmonary disease through weakening of the respiratory mucus-ciliary transport system, impairing cough reflex sensitivity, and inducing inflammation. Recent researches have indicated that hydrogen sulfide is essential in the development of various lung diseases. However, the effect and mechanism of hydrogen sulfide on cigarette smoke-induced chronic obstructive pulmonary disease have not been reported. In this study, rats were treated with cigarette smoke to create a chronic obstructive pulmonary disease model followed by treatment with a low concentration of hydrogen sulfide. Pulmonary function, histopathological appearance, lung edema, permeability, airway remodeling indicators, oxidative products/antioxidases levels, inflammatory factors in lung, cell classification in bronchoalveolar lavage fluid were measured to examine the effect of hydrogen sulfide on chronic obstructive pulmonary disease model. The results showed that hydrogen sulfide effectively improved pulmonary function and reduced histopathological changes, lung edema, and permeability. Airway remodeling, oxidative stress, and inflammation were also reduced by hydrogen sulfide treatment. To understand the mechanisms, we measured the expression of TGF-β1, TGF-βIand TGF-βII receptors and Smad7 and phosphorylation of Smad2/Smad3. The results indicated that the TGF-β1 and Smad were activated in cigarette smoke-induced chronic obstructive pulmonary disease model, but inhibited by hydrogen sulfide. In conclusion, this study showed that hydrogen sulfide treatment alleviated cigarette smoke-induced chronic obstructive pulmonary disease through inhibition of the TGF-β1/Smad pathway. Impact statement COPD has become a severe public health issue in the world and smoking has become a major cause of COPD. As a result, it is a demandingly needed to explore new potential therapy for cigarette smoke-associated COPD. The present study suggested that H2S treatment improved pulmonary function and reduced histopathological changes, lung edema, permeability, inflammation, airway remodeling and oxidative injury in a COPD model induced by cigarette smoke. Although additional studies are required to elucidate the pharmacodynamics, pharmacokinetics, and pharmacology of H2S in the cigarette smoke-associated COPD, our findings provide an experimental basis for the potential clinical application of H2S in COPD treatment.

Section: Discussionsupporting

confidence: 80%

Hydrogen sulfide alleviates cigarette smoke-induced COPD through inhibition of the TGF-β1/smad pathway

Meng

et al. 2020

Exp Biol Med (Maywood)

“…The TNF signaling pathway is linked to cardiac remodeling following MI (48). It has been found that TNF-α is involved in the pathogenesis and progression of MF (49). The clinical trial testing of anti-TNF-α drugs has been performed in patients with chronic HF (50,51).…”

Section: Discussionmentioning

confidence: 99%

Uncovering Potential lncRNAs and mRNAs in the Progression From Acute Myocardial Infarction to Myocardial Fibrosis to Heart Failure

Front. Cardiovasc. Med.

Chen

et al. 2021

Background: Morbidity and mortality of heart failure (HF) post-myocardial infarction (MI) remain elevated. The aim of this study was to find potential long non-coding RNAs (lncRNAs) and mRNAs in the progression from acute myocardial infarction (AMI) to myocardial fibrosis (MF) to HF.Methods: Firstly, blood samples from AMI, MF, and HF patients were used for RNA sequencing. Secondly, differentially expressed lncRNAs and mRNAs were obtained in MF vs. AMI and HF vs. MF, followed by functional analysis of shared differentially expressed mRNAs between two groups. Thirdly, interaction networks of lncRNA-nearby targeted mRNA and lncRNA-co-expressed mRNA were constructed in MF vs. AMI and HF vs. MF. Finally, expression validation and diagnostic capability analysis of selected lncRNAs and mRNAs were performed.Results: Several lncRNA-co-expressed/nearby targeted mRNA pairs including AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 were identified. Several signaling pathways including TNF and cytokine–cytokine receptor interaction, fructose and mannose metabolism and HIF-1, hematopoietic cell lineage and fluid shear stress, and atherosclerosis and estrogen were selected. IL1R2, IRAK3, LRG1, and PLAC4 had a potential diagnostic value for both AMI and HF.Conclusion: Identified AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 lncRNA-co-expressed/nearby targeted mRNA pairs may play crucial roles in the development of AMI, MF, and HF.

Oxidative Medicine and Cellular Longevity

“…The low concentration of H 2 S may cause oxidative stress, resulting in the depletion of tetrahydrobiopterin, which determines the levels of endothelial nitric oxide synthase (eNOS) activity [48]. As latent matrix metalloproteinases (MMPs) can be activated by oxidative stress [49], 2 Oxidative Medicine and Cellular Longevity ↓Canonical Wnt pathway-TGF-β1/SMAD3 pathway [114] ↑PKC-ERK1/2MAPK signaling pathway [127] ↓ER stress [115] ↓Autophagy via the upregulation of the PI3K/AKT1 pathway [116] Diabetes (type II) ↓Cardiac muscle degradation via sulfhydration of MuRF1 [128] Hypertension ↓Inflammatory response [103] ↓Extracellular matrix accumulation and ↑vascular density [129] ↓Nox4-ROS-ERK1/2 pathway and ↑HO-1…”

Section: Functional Roles Of H 2 S In the Biological System H 2 Smentioning

confidence: 99%

Hydrogen Sulfide as a Potential Alternative for the Treatment of Myocardial Fibrosis

Kang

Sohn

Lee

2020

Harmful, stressful conditions or events in the cardiovascular system result in cellular damage, inflammation, and fibrosis. Currently, there is no targeted therapy for myocardial fibrosis, which is highly associated with a large number of cardiovascular diseases and can lead to fatal heart failure. Hydrogen sulfide (H2S) is an endogenous gasotransmitter similar to nitric oxide and carbon monoxide. H2S is involved in the suppression of oxidative stress, inflammation, and cellular death in the cardiovascular system. The level of H2S in the body can be boosted by stimulating its synthesis or supplying it exogenously with a simple H2S donor with a rapid- or slow-releasing mode, an organosulfur compound, or a hybrid with known drugs (e.g., aspirin). Hypertension, myocardial infarction, and inflammation are exaggerated when H2S is reduced. In addition, the exogenous delivery of H2S mitigates myocardial fibrosis caused by various pathological conditions, such as a myocardial infarct, hypertension, diabetes, or excessive β-adrenergic stimulation, via its involvement in a variety of signaling pathways. Numerous experimental findings suggest that H2S may work as a potential alternative for the management of myocardial fibrosis. In this review, the antifibrosis role of H2S is briefly addressed in order to gain insight into the development of novel strategies for the treatment of myocardial fibrosis.