{"title":"PM2.5 暴露进一步加剧尿毒症心肌病心肌缺血再灌注损伤的恶化:线粒体是病理学的中心焦点","authors":"Bhavana Sivakumar, Gino A. Kurian","doi":"10.1007/s12012-024-09920-y","DOIUrl":null,"url":null,"abstract":"<p>Uremic cardiomyopathy (UC) represents a complex syndrome characterized by different cardiac complications, including systolic and diastolic dysfunction, left ventricular hypertrophy, and diffuse fibrosis, potentially culminating in myocardial infarction (MI). Revascularization procedures are often necessary for MI management and can induce ischemia reperfusion injury (IR). Despite this clinical relevance, the role of fine particulate matter (PM<sub>2.5</sub>) in UC pathology and the underlying subcellular mechanisms governing this pathology remains poorly understood. Hence, we investigate the impact of PM<sub>2.5</sub> exposure on UC susceptibility to IR injury. Using a rat model of adenine-induced chronic kidney disease (CKD), the animals were exposed to PM<sub>2.5</sub> at 250 µg/m<sup>3</sup> for 3 h daily over 21 days. Subsequently, hearts were isolated and subjected to 30 min of ischemia followed by 60 min of reperfusion to induce IR injury. UC hearts exposed to PM<sub>2.5</sub> followed by IR induction (Adenine + PM_IR) exhibited significantly impaired cardiac function and increased cardiac injury (increased infarct size and apoptosis). Analysis at the subcellular level revealed reduced mitochondrial copy number, impaired mitochondrial bioenergetics, decreased expression of PGC1-α (a key regulator of mitochondrial biogenesis), and compromised mitochondrial quality control mechanisms. Additionally, increased mitochondrial oxidative stress and perturbation of the PI3K/AKT/AMPK signaling axis were evident. Our findings therefore collectively indicate that UC myocardium when exposed to PM<sub>2.5</sub> is more vulnerable to IR-induced injury, primarily due to severe mitochondrial impairment.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Worsening of Myocardial Ischemia–Reperfusion Injury in Uremic Cardiomyopathy is Further Aggravated by PM2.5 Exposure: Mitochondria Serve as the Central Focus of Pathology\",\"authors\":\"Bhavana Sivakumar, Gino A. Kurian\",\"doi\":\"10.1007/s12012-024-09920-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Uremic cardiomyopathy (UC) represents a complex syndrome characterized by different cardiac complications, including systolic and diastolic dysfunction, left ventricular hypertrophy, and diffuse fibrosis, potentially culminating in myocardial infarction (MI). Revascularization procedures are often necessary for MI management and can induce ischemia reperfusion injury (IR). Despite this clinical relevance, the role of fine particulate matter (PM<sub>2.5</sub>) in UC pathology and the underlying subcellular mechanisms governing this pathology remains poorly understood. Hence, we investigate the impact of PM<sub>2.5</sub> exposure on UC susceptibility to IR injury. Using a rat model of adenine-induced chronic kidney disease (CKD), the animals were exposed to PM<sub>2.5</sub> at 250 µg/m<sup>3</sup> for 3 h daily over 21 days. Subsequently, hearts were isolated and subjected to 30 min of ischemia followed by 60 min of reperfusion to induce IR injury. UC hearts exposed to PM<sub>2.5</sub> followed by IR induction (Adenine + PM_IR) exhibited significantly impaired cardiac function and increased cardiac injury (increased infarct size and apoptosis). Analysis at the subcellular level revealed reduced mitochondrial copy number, impaired mitochondrial bioenergetics, decreased expression of PGC1-α (a key regulator of mitochondrial biogenesis), and compromised mitochondrial quality control mechanisms. Additionally, increased mitochondrial oxidative stress and perturbation of the PI3K/AKT/AMPK signaling axis were evident. Our findings therefore collectively indicate that UC myocardium when exposed to PM<sub>2.5</sub> is more vulnerable to IR-induced injury, primarily due to severe mitochondrial impairment.</p>\",\"PeriodicalId\":9570,\"journal\":{\"name\":\"Cardiovascular Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cardiovascular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12012-024-09920-y\",\"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":"Cardiovascular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12012-024-09920-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
The Worsening of Myocardial Ischemia–Reperfusion Injury in Uremic Cardiomyopathy is Further Aggravated by PM2.5 Exposure: Mitochondria Serve as the Central Focus of Pathology
Uremic cardiomyopathy (UC) represents a complex syndrome characterized by different cardiac complications, including systolic and diastolic dysfunction, left ventricular hypertrophy, and diffuse fibrosis, potentially culminating in myocardial infarction (MI). Revascularization procedures are often necessary for MI management and can induce ischemia reperfusion injury (IR). Despite this clinical relevance, the role of fine particulate matter (PM2.5) in UC pathology and the underlying subcellular mechanisms governing this pathology remains poorly understood. Hence, we investigate the impact of PM2.5 exposure on UC susceptibility to IR injury. Using a rat model of adenine-induced chronic kidney disease (CKD), the animals were exposed to PM2.5 at 250 µg/m3 for 3 h daily over 21 days. Subsequently, hearts were isolated and subjected to 30 min of ischemia followed by 60 min of reperfusion to induce IR injury. UC hearts exposed to PM2.5 followed by IR induction (Adenine + PM_IR) exhibited significantly impaired cardiac function and increased cardiac injury (increased infarct size and apoptosis). Analysis at the subcellular level revealed reduced mitochondrial copy number, impaired mitochondrial bioenergetics, decreased expression of PGC1-α (a key regulator of mitochondrial biogenesis), and compromised mitochondrial quality control mechanisms. Additionally, increased mitochondrial oxidative stress and perturbation of the PI3K/AKT/AMPK signaling axis were evident. Our findings therefore collectively indicate that UC myocardium when exposed to PM2.5 is more vulnerable to IR-induced injury, primarily due to severe mitochondrial impairment.
期刊介绍:
Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.