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Exogenous H2S restores ischemic post-conditioning-induced cardioprotection through inhibiting endoplasmic reticulum stress in the aged cardiomyocytes

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Exogenous H2S restores ischemic post-conditioning-induced ca...

Regenerative potential of mouse embryonic stem cell-derived PDGFRα+ cardiac lineage committed cells in infarcted myocardium

第十一届海峡两岸心血管科学研讨会、2017年全国心脑血管药理学术会议、中国卒中学会第一次新药研讨会

作者： Sun Weiming Yang Jinxia Zhang Yuanzhou Li Lina Yuan Di Wang Yuehong Wei Can Wang Rui Wu Lingyun Xu Changqing Li Hongzhu Department of Pathophysiology Harbin Medical University The Key Laboratory of cardiovascular Medicine research(Harbin Medical University) Ministry of Education Department of Pathology Daqing Medical College The cardiovascular and metabolic research unit Laurentian University

Aim:Gas signal molecule hydrogen sulfide（H S） plays an important physiological and pathological role in cardiovascular *** post-conditioning（PC） provides cardioprotection in the young hearts but not in the aged *** H S restores PC-induced cardioprotection by inhibition of mitochondrial permeability transition pore（mPTP） opening and oxidative stress and increase of

关键词： Exogenous H2S restores ischemic post-conditioning-induced cardioprotection through inhibiting endoplasmic reticulum stress in the aged cardiomyocytes

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World Journal of Stem Cells 2019年第1期11卷 44-54页

作者： Seon Pyo Hong Sukhyun Song Seungjoo Lee Hyeonju Jo Hyoung Kyu Kim Jin Han Jae-Hyeong Park Sung Woo Cho Center for Vascular research Institute of Basic Science (IBS)Daejeon Department of Neurosurgery Asan Medical Center University of Ulsan College of Medicine cardiovascular and metabolic Disease Center Department of Physiology Department of Health Sciences and Technology BK21 plus Project Team Inje University College of Medicine Department of Cardiology in Internal Medicine School of MedicineChungnam National University Hospital Chungnam National University Division of Cardiology Department of Internal Medicine Inje University College of Medicine Seoul Paik Hospital cardiovascular and metabolic Disease Center Inje University College of Medicine

BACKGROUND Pluripotent stem cell-derived cardiomyocytes(CMs) have become one of the most attractive cellular resources for cell-based therapy to rescue damaged cardiac *** We investigated the regenerative potential of mouse embryonic stem cell(ESC)-derived platelet-derived growth factor receptor-α(PDGFRα)+ cardiac lineagecommitted cells(CLCs), which have a proliferative capacity but are in a morphologically and functionally immature state compared with differentiated *** induced mouse ESCs into PDGFRα+ CLCs and αMHC+ CMs using a combination of the small molecule cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor *** implanted PDGFRα+ CLCs and differentiated αMHC+ CMs into a myocardial infarction(MI) murine model and performed functional analysis using transthoracic echocardiography(TTE) and histologic *** Compared with the untreated MI hearts, the anterior and septal regional wall motion and systolic functional parameters were notably and similarly improved in the MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs based on *** histologic analysis, the untreated MI hearts contained a thinner ventricular wall than did the controls, while the ventricular walls of MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs were similarly thicker compared with that of the untreated MI hearts. Furthermore, implanted PDGFRα+ CLCs aligned and integrated with host CMs and were mostly differentiated into α-actinin+ CMs,and they did not convert into CD31+ endothelial cells or αSMA+ mural *** PDGFRα+ CLCs from mouse ESCs exhibiting proliferative capacity showed a regenerative effect in infarcted myocardium. Therefore, mouse ESC-derived PDGFRα+ CLCs may represent a potential cellular resource for cardiac regeneration.

关键词： Pluripotent stem cell Embryonic stem cell Cardiomyocyte Myocardial infarction Regeneration

Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages

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Cellular & Molecular Immunology 2023年第2期20卷 131-142页

作者： Chia George Hsu Wenjia Li Mark Sowden Camila Lage Chávez Bradford C.Berk Department of Medicine Aab Cardiovascular Research InstituteUniversity of RochesterRochesterNYUSA Department of cardiovascular Medicine Ruijin HospitalShanghai Jiao Tong University School of Medicine200025ShanghaiChina

Polyribonucleotide nucleotidyltransferase 1(Pnpt1)plays critical roles in mitochondrial homeostasis by controlling mitochondrial RNA(mt-RNA)processing,trafficking and ***1 deficiency results in mitochondrial dysfunction that triggers a type I interferon response,suggesting a role in ***,the role of Pnpt1 in inflammasome activation remains largely *** this study,we generated myeloid-specific Pnpt1-knockout mice and demonstrated that Pnpt1 depletion enhanced interleukin-1 beta(IL-1β)and interleukin-18(IL-18)secretion in a mouse sepsis *** cultured peritoneal and bone marrow-derived macrophages,we demonstrated that Pnpt1 regulated NLRP3 inflammasome-dependent IL-1βrelease in response to lipopolysaccharide(LPS),followed by nigericin,ATP or poly(I:C)***1 deficiency in macrophages increased glycolysis after LPS administration and mt-reactive oxygen species(mt-ROS)after NLRP3 inflammasome ***1 activation of the inflammasome was dependent on increased glycolysis and the expression of mitochondrial antiviral-signaling protein(MAVS)but not NF-κB ***,these data suggest that Pnpt1 is an important mediator of inflammation,as shown by activation of the NLRP3 inflammasome in murine sepsis and cultured macrophages.

关键词： Pnpt1 Inflammasome Mitochondria Macrophage

Risk Factors for Diabetes and cardiovascular Complications in the Chinese Population

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China CDC weekly 2023年第45期5卷 1017-1021页

作者： Chun Dou Dong Liu Tiange Wang Department of Endocrine and metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Shanghai National Clinical research Center for metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR ChinaShanghai Key Laboratory for Endocrine TumorRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina.

Type 2 diabetes,a major noncommunicable disease,is typified by hyperglycemia,which stems from insulin resistance and dysfunction of pancreaticβ-cells(1).Prior multi-ethnic studies hypothesized that type 2 diabetes among Caucasians was primarily driven by insulin resistance,whereas in East Asians,it was predominantly a consequence ofβ-cell dysfunction(2).Apart from the apparent genetic variations,obesity has been identified as the main factor responsible for the pathophysiological differences in diabetes between Caucasians and East Asians(3).Notably,China has seen a considerable increase in obesity cases in congruence with substantial changes in lifestyle and urbanization over the last four *** a recent population-based national cohort study,we showed that insulin resistance,rather thanβ-cell dysfunction,had a significant role in the pathological progression of diabetes within the Chinese population(1).This correlation was particularly pronounced among obese adults(1).

关键词： obesity sized consequence

Development of cystathionine gamma-lyase-specific microRNAs

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Science Bulletin 2015年第5期60卷 503-510页

作者：李双双杨广东 cardiovascular and metabolic research unit Lakehead University Thunder Bay P7B 5E1 Canada School of Kinesiology Lakehead UniversityThunder Bay P7B 5E1 Canada

The gasotransmitter role of H2S in mammalian has been extensively studied, and cystathionine gammalyase （CSE） is the major H2S-producing enzyme in vascular system. Dysregulation of CSE/H2S system was found in various pathophysiological conditions. MicroRNA （miRNA） and short interfering RNA （siRNA） are known to inhibit gene expression by mRNA degradation and/or translation repression. The regulation of CSE expression by miRNA and siRNA has been reported recently, but the off-target effect of miRNA and the lower knockdown efficiency of siRNA have shadowed the application of these approaches. In the present study, we designed CSE-specific miRNAs based on the rules of miRNA-mRNA complementary and human CSE cDNA sequence. The CSE-specific miRNAs significantly inhibited CSE expression and H2S production, increased reactive oxygen species generation, and induced proliferation of human aorta smooth muscle cells （HASMCs）. The designed CSE-specific miRNAs specifically targeted on CSE gene as evidenced by the direct inhibition of luciferase activity from reporter gene containing human CSE 3t-UTR sequence. The expression of other genes, such as estrogen receptor a, heme oxygenase 1, specificity protein 1, and 3-mercaptopyruvate sulfurtransferase, was not affected by the CSE-specific *** with CSE-siRNAs, CSE-specific miRNAs dis- played significantly higher efficacy in suppressing CSE expression and H2S production, miR-143, a highly expressed miRNA in vascular system, down-regulated the expressions of CSE as well as other genes, such as insulin-like growth factor binding protein 5 and kruppel-like factor 4. miR-143 suppressed H2S production but had no effect on HASMC proliferation. In conclusion, CSE-specific miRNAs designed in our study provide a highly effective research tool for regulating CSE expression and H2S production. These CSE-specific miRNAs have potential as being novel therapeutic agents for treating vascular disorders related to abnormal oxidative stress

关键词： H2S Cystathionine gamma-lyase MicroRNAs siRNA Smooth muscle cells

Incretins and selective renal sodium-glucose co-transporter 2 inhibitors in hypertension and coronary heart disease

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World Journal of Diabetes 2015年第11期6卷 1186-1197页

作者： Ramiro A Sanchez Hugo Sanabria Cecilia de los Santos Agustin J Ramirez Arterial Hypertension and metabolic unit University Hospital Fundación Favaloro Diabetes unit Instituto Cardiovascular de Buenos Aires Santos Medical Affairs Department Boehringer Ingelheim

Hyperglycemia is associated with an increased risk of cardiovascular disease,and the consequences ofintensive therapy may depend on the mechanism of the anti-diabetic agent(s)used to achieve a tight *** animal models,stable analogues of glucagon-like peptide-1(GLP-1)were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary *** a similar way,dipeptidyl peptidase IV(DPPIV)showed to have favorable effects in animal models of ischemia/*** could be due to the fact that DPPIV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide,but they also decreased the degradation of several vasoactive *** data for GLP-1,its derivatives and inhibitors of the DPPIV enzyme degradation suggests that these agents may be able to,besides controlling glycaemia,induce cardio-protective and vasodilator *** the many favorable cardiovascular effects of GLP-1/incretins reported in different studies,many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular *** this reason,long-term trials searching for positive cardiovascular effects are now in process,such as the CAROLINA and CARMELINA trials,which are supported by small pilot studies performed in humans(and many more animal studies)with incretin-based *** the other hand,selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 ***,it is quite early to draw conclusions,since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still *** this review,we will analyze the mechanisms underlying the cardiovascular effects of incretins and,at the same time,we will present a critical position about the real value of these compounds in the cardiovas

关键词： Incretins Hypertension cardiovascular effects Dipe

LncRNA MIAT impairs cardiac contractile function by acting on mitochondrial translocator protein TSPO in a mouse model of myocardial infarction

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1653-1656页

作者： Xue Bai Chao Yang Lei Jiao Hongtao Diao Ziyu Meng Lei Wang Hao Cui Lihua Sun Yong Zhang Baofeng Yang Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China and Key Laboratory of cardiovascular Medicine research Ministry of Education)College of PharmacyHarbin Medical UniversityHarbinHeilongjiangP.R.China Institute of metabolic Disease Heilongjiang Academy of Medical ScienceHarbinChina

Dear Editor,Long non-coding RNA MIAT(IncR-MIAT)has recently been identified as a risk factor for myocardial infarction(Ml).1 However,how IncR-MIAT controls Ml remained yet to be *** shed light on this issue,we firstly detected the expression of IncR-MIAT using qRT-PCR and found a robust elevation(>5-fold)of IncR-MIAT level in heart of Ml mice relative to sham-operated control counterparts(Supplementary Fig.S1a). MIAT in NMVCs(Supplementary ***).

关键词： infarction myocardial LncRNA

Calcium sensing receptor protects high glucose-induced energy metabolism disorder via blocking gp78-ubiquitin proteasome pathway

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Calcium sensing receptor protects high glucose-induced energ...

Microbial transformations of bile acids and their receptors in the regulation of metabolic dysfunction-associated steatotic liver disease

第十一届海峡两岸心血管科学研讨会、2017年全国心脑血管药理学术会议、中国卒中学会第一次新药研讨会

作者： Wang Yuehong Gao Ping Wei Can Li Hongzhu Zhang Li Zhao Yajun Wu Bo Tian Ye Zhang Weihua Wu Lingyun Wang Rui Xu Changqing Harbin Medical University Department of Endocrinology The Second Affiliated Hospital of Harbin Medical University The cardiovascular and metabolic research unit Laurentian University Health Sciences North research Institute

Aim Diabetic cardiomyopathy(DCM) is a major complication and fatal cause of the patients with *** calcium sensing receptor(CaSR) is a G protein-coupled receptor,which is involved in maintaining calcium homeostasis,regulating cell proliferation and apoptosis,and so *** our previous study,we found that CaSR expression,intracellular calcium levels and cardiac function were

关键词： Calcium sensing receptor protects high glucose-induced energy metabolism disorder via blocking gp78-ubiquitin proteasome pathway ATP

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Liver research 2023年第3期7卷 165-176页

作者： Yuhua Gao Jun Lin Chuan Ye Siqi Guo Changtao Jiang Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking Universityand the Key Laboratory of Molecular Cardiovascular Science(Peking University)Ministry of EducationBeijingChina Center of Basic Medical research Institute of Medical Innovation and ResearchThird HospitalPeking UniversityBeijingChina Center for Obesity and metabolic Disease research School of Basic Medical SciencesPeking UniversityBeijingChina

Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic *** the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological ***,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA *** of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.

关键词： Bile acids(BAs) Gut microbiota metabolic dysfunction-associated steatotic liver disease(MASLD) metabolic dysfunction-associated steatohepatitis(MASH) Hepatocellular carcinoma(HCC) Farnesoid X receptor(FXR) G protein-coupled bile acid receptor 1(TGR5)