Hydrogen sulfide alleviates high-salt-stimulated myocardial fibrosis through inhibiting hypoxia-inducible factor-1α.

Background: Endogenous hydrogen sulfide (HS) and its key generating enzyme, cystathionine β-synthase (CBS), prevent vascular remodeling and damage to target organs during the advancement of hypertension induced by a high-salt diet.

Objective: The contribution of the HS/CBS pathway to high-salt-induced myocardial fibrosis (MF) was explored, with a focus on the mechanistic involvement of hypoxia-inducible factor-1α (HIF-1α).

Methods: We used primary rat cardiac fibroblasts stimulated with high-salt medium and an MF model induced by a high-salt diet in Dahl salt-sensitive rats.

Intermedin improves aging-associated cardiac remodeling and dysfunction via mitochondrial SIRT3-mediated SOD2 deacetylation.

The aging-associated cardiac remodeling (AACR) is characterized by myocardial hypertrophy, fibrosis and cardiac dysfunction, which could be further aggravated by angiotensin II (Ang II) and pressure-overload in aged people. In this study, we aimed to investigate the roles and mechanisms of intermedin (IMD), an endogenous peptide, in AACR in aged mice (18 months) with subcutaneous Ang II infusion (1000 ng/kg/min) for 2 weeks via osmotic pump or transverse abdominal aorta constriction (AAC) surgery for 4 weeks. In aged mice undergoing Ang II infusion or AAC surgery, the results showed that the mRNA and protein levels of IMD were significantly reduced, but the protein levels of its receptor complex components were increased; blood pressure (BP), myocardial hypertrophy, fibrosis, and cardiac dysfunction were notably aggravated; mitochondrial Sirtuin 3 (SIRT3) protein level, superoxide dismutase 2 (SOD2) activity and ATP production were remarkably decreased, but acetylated SOD2 (acSOD2) protein level was markedly increased when compared with the old mice.

Vascular smooth muscle cell-derived SO sulphenylated interferon regulatory factor 1 to inhibit VSMC senescence.

Background: Vascular smooth muscle cell (VSMC) senescence is a critical driver of vascular aging and various age-related cardiovascular diseases. Endogenous sulfur dioxide (SO), a newly identified key cardiovascular gaseous signaling mediator, accelerates collagen deposition and vascular remodeling in VSMCs when downregulated. However, its effects on VSMC senescence remain unclear.

Endogenous hydrogen sulfide persulfidates endothelin type A receptor to inhibit pulmonary arterial smooth muscle cell proliferation.

Background: The binding of endothelin-1 (ET-1) to endothelin type A receptor (ETAR) performs a critical action in pulmonary arterial smooth muscle cell (PASMC) proliferation leading to pulmonary vascular structural remodeling. More evidence showed that cystathionine γ-lyase (CSE)-catalyzed endogenous hydrogen sulfide (HS) was involved in the pathogenesis of cardiovascular diseases. In this study, we aimed to explore the effect of endogenous HS/CSE pathway on the ET-1/ETAR binding and its underlying mechanisms in the cellular and animal models of PASMC proliferation.

Systematic analysis of the global characteristics and reciprocal effects of S-nitrosylation and S-persulfidation in the human proteome.

Gasotransmitter-mediated cysteine post-translational modifications, including S-nitrosylation (SNO) and S-persulfidation (SSH), play crucial roles and interact in various biological processes. However, there has been a delay in appreciating the interactional rules between SNO and SSH. Here, all human S-nitrosylated and S-persulfidated proteomic data were curated, and comprehensive analyses from multiple perspectives, including sequence, structure, function, and exact protein impacts (e.

Endogenous sulfur dioxide deficiency as a driver of cardiomyocyte senescence through abolishing sulphenylation of STAT3 at cysteine 259.

Objective: Cardiomyocyte senescence is an important contributor to cardiovascular diseases and can be induced by stressors including DNA damage, oxidative stress, mitochondrial dysfunction, epigenetic regulation, etc. However, the underlying mechanisms for the development of cardiomyocyte senescence remain largely unknown. Sulfur dioxide (SO) is produced endogenously by aspartate aminotransferase 2 (AAT2) catalysis and plays an important regulatory role in the development of cardiovascular diseases.

Intermedin alleviates diabetic vascular calcification by inhibiting GLUT1 through activation of the cAMP/PKA signaling pathway.

Background And Aims: Vascular calcification (VC) is regarded as an independent risk factor for cardiovascular events in type 2 diabetic patients. Glucose transporter 1 (GLUT1) involves VC. Intermedin/Adrenomedullin-2 (IMD/ADM2) is a cardiovascular protective peptide that can inhibit multiple disease-associated VC.

L-cystathionine protects against oxidative stress and DNA damage induced by oxidized low-density lipoprotein in THP-1-derived macrophages.

Oxidative stress in monocyte-derived macrophages is a significant pathophysiological process in atherosclerosis. L-cystathionine (L-Cth) acts as a scavenger for oxygen free radicals. However, the impact of L-Cth on macrophage oxidative stress during atherogenesis has remained unclear.

A predictive model of response to metoprolol in children and adolescents with postural tachycardia syndrome.

Background: The present work was designed to explore whether electrocardiogram (ECG) index-based models could predict the effectiveness of metoprolol therapy in pediatric patients with postural tachycardia syndrome (POTS).

Methods: This study consisted of a training set and an external validation set. Children and adolescents with POTS who were given metoprolol treatment were enrolled, and after follow-up, they were grouped into non-responders and responders depending on the efficacy of metoprolol.

Hydrogen Sulfide Biomedical Research in China-20 Years of Hindsight.

Hydrogen sulfide (HS) is an important gasotransmitter that is produced by mammalian cells and performs profound physiological and pathophysiological functions. Biomedical research on HS metabolism and function in China began 20 years ago, which pioneered the examination of the correlation of abnormal HS metabolism and cardiovascular diseases. Over the last two decades, research teams in China have made numerous breakthrough discoveries on the effects of HS metabolism on hypertension, atherosclerosis, pulmonary hypertension, shock, angiogenesis, chronic obstructive pulmonary disease, pain, iron homeostasis, and testicle function, to name a few.

Plasma human growth cytokines in children with vasovagal syncope.

Purpose: The study was designed to investigate the profile of plasma human growth cytokines in pediatric vasovagal syncope (VVS).

Materials And Methods: In the discovery set of the study, plasma human growth cytokines were measured using a Quantiboby Human Growth Factor Array in 24 VVS children and 12 healthy controls. Scatter and principal component analysis (PCA) diagrams were used to describe the samples, an unsupervised hierarchical clustering analysis was used to categorize the samples.

Intermedin Alleviates Vascular Calcification in CKD through Sirtuin 3-Mediated Inhibition of Mitochondrial Oxidative Stress.

Vascular calcification (VC) is a common pathophysiological process of chronic kidney disease (CKD). Sirtuin 3 (Sirt3), a major NAD-dependent protein deacetylase predominantly in mitochondria, is involved in the pathogenesis of VC. We previously reported that intermedin (IMD) could protect against VC.

Implications of Hydrogen Sulfide in Development of Pulmonary Hypertension.

The pathological mechanisms underlying pulmonary hypertension (PH), as well as its treatment strategy, are crucial issues in this field. This review aimed to summarize the pathological mechanisms by which the hydrogen sulfide (HS) pathway contributes to PH development and its future implications. The data in this review were obtained from Medline and PubMed sources up to 2022 using the search terms "hydrogen sulfide" and "pulmonary hypertension".

Hydrogen Sulfide Regulates Macrophage Function in Cardiovascular Diseases.

Hydrogen sulfide (HS) is an endogenous gasotransmitter that plays a vital role in immune system regulation. Recently, the regulation of macrophage function by HS has been extensively and actively recognized. The mechanisms by which endogenous HS controls macrophage function have attracted increasing attention.

Endogenous Hydrogen Sulfide Persulfidates Caspase-3 at Cysteine 163 to Inhibit Doxorubicin-Induced Cardiomyocyte Apoptosis.

Doxorubicin (DOX) is an efficient antitumor anthracycline drug, but its cardiotoxicity adversely affects the prognosis of the patients. In this study, we explored whether endogenous gasotransmitter hydrogen sulfide (HS) could protect against DOX-induced cardiomyocyte apoptosis and its mechanisms. The results indicated that DOX significantly downregulated endogenous HS production and endogenous synthetase cystathionine -lyase (CSE) expression and obviously stimulated the apoptosis in H9C2 cells.

Correction: Transcriptional Effects of E3 Ligase Atrogin-1/MAFbx on Apoptosis, Hypertrophy and Inflammation in Neonatal Rat Cardiomyocytes.

[This corrects the article DOI: 10.1371/journal.pone.

Risk factors of sitting-induced tachycardia syndrome in children and adolescents.

Background: The study was designed to explore the risk factors for sitting-induced tachycardia syndrome (STS) in children and adolescents.

Methods And Results: In this case-control study, 46 children with STS and 184 healthy children and adolescents were recruited. Demographic characteristics, lifestyle habits, allergy history, and family history were investigated using a questionnaire.

Intermedin Inhibits NLRP3 Inflammasome Activation by Targeting IRE1α in Cardiac Fibrosis.

Intermedin (IMD), a paracrine/autocrine peptide, protects against cardiac fibrosis. However, the underlying mechanism remains poorly understood. Previous study reports that activation of nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributes to cardiac fibrosis.

Baseline Corrected QT Interval Dispersion Is Useful to Predict Effectiveness of Metoprolol on Pediatric Postural Tachycardia Syndrome.

Objectives: The study was designed to explore the role of baseline-corrected QT interval dispersion (QTcd) in predicting the effectiveness of metoprolol on pediatric postural tachycardia syndrome (POTS).

Methods: There were two groups in the study, the discovery group and the validation group. The children with POTS in the discovery group were treated with oral metoprolol, with the completed necessary medical records, head-up tilt test (HUTT), blood chemistry, and 12-lead ECG before treatment at the pediatrics of Peking University First Hospital, China.

Sulphenylation of CypD at Cysteine 104: A Novel Mechanism by Which SO Inhibits Cardiomyocyte Apoptosis.

The study was designed to explore the role of endogenous gaseous signaling molecule sulfur dioxide (SO) in the control of cardiomyocyte apoptosis and its molecular mechanisms. Neonatal mouse cardiac myocytes (NMCMs) and H9c2 cells were used in the cell experiments. The endogenous SO pathway including SO level and the expression of SO-generating enzyme aspartate aminotransferase 1/2 (AAT1/2) were detected in NMCMs.

Compensatory role of endogenous sulfur dioxide in nitric oxide deficiency-induced hypertension.

Objective: This study aimed to determine the communicational pattern of gaseous signaling molecules sulfur dioxide (SO) and nitric oxide (NO) between vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), and elucidate the compensatory role and significance of endogenous SO in the development of hypertension due to NO deficiency.

Approach And Results: Blood pressure was monitored by the tail-cuff and implantable physiological signal telemetry in L-nitro-arginine methyl ester (l-NAME)-induced hypertensive mice, and structural alterations of mouse aortic vessels were detected by the elastic fiber staining method. l-NAME-treated mice showed decreased plasma NO levels, increased SO levels, vascular remodeling, and increased blood pressure, and application of l-aspartate-β-hydroxamate, which inhibits SO production, further aggravated vascular structural remodeling and increased blood pressure.

Sulfur Dioxide: Endogenous Generation, Biological Effects, Detection, and Therapeutic Potential.

Previously, sulfur dioxide (SO) was recognized as an air pollutant. However, it is found to be endogenously produced in mammalian tissues. As a new gasotransmitter, SO is involved in regulating the structure and function of blood vessels, heart, lung, gastrointestinal tract, nervous system, Increasing evidence showed that endogenous SO regulates cardiovascular physiological processes, such as blood pressure control, vasodilation, maintenance of the normal vascular structure, and cardiac negative inotropy.

Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy.

Background: Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.

Methods: This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019.

Interaction among Hydrogen Sulfide and Other Gasotransmitters in Mammalian Physiology and Pathophysiology.

Hydrogen sulfide (HS), nitric oxide (NO), carbon monoxide (CO), and sulfur dioxide (SO) were previously considered as toxic gases, but now they are found to be members of mammalian gasotransmitters family. Both HS and SO are endogenously produced in sulfur-containing amino acid metabolic pathway in vivo. The enzymes catalyzing the formation of HS are mainly CBS, CSE, and 3-MST, and the key enzymes for SO production are AAT1 and AAT2.