Eng Leng Saw, Martin Fronius, Rajesh Katare, Yoshihiko Kakinuma
{"title":"微型综述:2 型糖尿病中的非神经元心脏胆碱能系统","authors":"Eng Leng Saw, Martin Fronius, Rajesh Katare, Yoshihiko Kakinuma","doi":"10.3389/fcvm.2024.1425534","DOIUrl":null,"url":null,"abstract":"Diabetic heart disease remains the leading cause of death in individuals with type-2 diabetes mellitus (T2DM). Both insulin resistance and metabolic derangement, hallmark features of T2DM, develop early and progressively impair cardiovascular function. These factors result in altered cardiac metabolism and energetics, as well as coronary vascular dysfunction, among other consequences. Therefore, gaining a deeper understanding of the mechanisms underlying the pathophysiology of diabetic heart disease is crucial for developing novel therapies for T2DM-associated cardiovascular disease. Cardiomyocytes are equipped with the cholinergic machinery, known as the non-neuronal cardiac cholinergic system (NNCCS), for synthesizing and secreting acetylcholine (ACh) as well as possessing muscarinic ACh receptor for ACh binding and initiating signaling cascade. ACh from cardiomyocytes regulates glucose metabolism and energetics, endothelial function, and among others, in an auto/paracrine manner. Presently, there is only one preclinical animal model – diabetic db/db mice with cardiac-specific overexpression of choline transferase (<jats:italic>Chat</jats:italic>) gene - to study the effect of activated NNCCS in the diabetic heart. In this mini-review, we discuss the physiological role of NNCCS, the connection between NNCCS activation and cardiovascular function in T2DM and summarize the current knowledge of S-Nitroso-NPivaloyl-D-Penicillamine (SNPiP), a novel inducer of NNCCS, as a potential therapeutic strategy to modulate NNCCS activity for diabetic heart disease.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mini Review: the non-neuronal cardiac cholinergic system in type-2 diabetes mellitus\",\"authors\":\"Eng Leng Saw, Martin Fronius, Rajesh Katare, Yoshihiko Kakinuma\",\"doi\":\"10.3389/fcvm.2024.1425534\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Diabetic heart disease remains the leading cause of death in individuals with type-2 diabetes mellitus (T2DM). Both insulin resistance and metabolic derangement, hallmark features of T2DM, develop early and progressively impair cardiovascular function. These factors result in altered cardiac metabolism and energetics, as well as coronary vascular dysfunction, among other consequences. Therefore, gaining a deeper understanding of the mechanisms underlying the pathophysiology of diabetic heart disease is crucial for developing novel therapies for T2DM-associated cardiovascular disease. Cardiomyocytes are equipped with the cholinergic machinery, known as the non-neuronal cardiac cholinergic system (NNCCS), for synthesizing and secreting acetylcholine (ACh) as well as possessing muscarinic ACh receptor for ACh binding and initiating signaling cascade. ACh from cardiomyocytes regulates glucose metabolism and energetics, endothelial function, and among others, in an auto/paracrine manner. Presently, there is only one preclinical animal model – diabetic db/db mice with cardiac-specific overexpression of choline transferase (<jats:italic>Chat</jats:italic>) gene - to study the effect of activated NNCCS in the diabetic heart. In this mini-review, we discuss the physiological role of NNCCS, the connection between NNCCS activation and cardiovascular function in T2DM and summarize the current knowledge of S-Nitroso-NPivaloyl-D-Penicillamine (SNPiP), a novel inducer of NNCCS, as a potential therapeutic strategy to modulate NNCCS activity for diabetic heart disease.\",\"PeriodicalId\":12414,\"journal\":{\"name\":\"Frontiers in Cardiovascular Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Cardiovascular Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fcvm.2024.1425534\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cardiovascular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fcvm.2024.1425534","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Mini Review: the non-neuronal cardiac cholinergic system in type-2 diabetes mellitus
Diabetic heart disease remains the leading cause of death in individuals with type-2 diabetes mellitus (T2DM). Both insulin resistance and metabolic derangement, hallmark features of T2DM, develop early and progressively impair cardiovascular function. These factors result in altered cardiac metabolism and energetics, as well as coronary vascular dysfunction, among other consequences. Therefore, gaining a deeper understanding of the mechanisms underlying the pathophysiology of diabetic heart disease is crucial for developing novel therapies for T2DM-associated cardiovascular disease. Cardiomyocytes are equipped with the cholinergic machinery, known as the non-neuronal cardiac cholinergic system (NNCCS), for synthesizing and secreting acetylcholine (ACh) as well as possessing muscarinic ACh receptor for ACh binding and initiating signaling cascade. ACh from cardiomyocytes regulates glucose metabolism and energetics, endothelial function, and among others, in an auto/paracrine manner. Presently, there is only one preclinical animal model – diabetic db/db mice with cardiac-specific overexpression of choline transferase (Chat) gene - to study the effect of activated NNCCS in the diabetic heart. In this mini-review, we discuss the physiological role of NNCCS, the connection between NNCCS activation and cardiovascular function in T2DM and summarize the current knowledge of S-Nitroso-NPivaloyl-D-Penicillamine (SNPiP), a novel inducer of NNCCS, as a potential therapeutic strategy to modulate NNCCS activity for diabetic heart disease.
期刊介绍:
Frontiers? Which frontiers? Where exactly are the frontiers of cardiovascular medicine? And who should be defining these frontiers?
At Frontiers in Cardiovascular Medicine we believe it is worth being curious to foresee and explore beyond the current frontiers. In other words, we would like, through the articles published by our community journal Frontiers in Cardiovascular Medicine, to anticipate the future of cardiovascular medicine, and thus better prevent cardiovascular disorders and improve therapeutic options and outcomes of our patients.