Xuesheng Fang, Jie Chen, Zhiling Hu, Ling Shu, Jing Wang, Mingyan Dai, Tuantuan Tan, Junxia Zhang, Mingwei Bao
{"title":"刺激颈动脉感受器可改善缺氧诱发肺动脉高压大鼠的肺动脉重塑","authors":"Xuesheng Fang, Jie Chen, Zhiling Hu, Ling Shu, Jing Wang, Mingyan Dai, Tuantuan Tan, Junxia Zhang, Mingwei Bao","doi":"10.1161/JAHA.124.035868","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Sympathetic hyperactivity plays an important role in the initiation and maintenance of pulmonary hypertension. Carotid baroreceptor stimulation (CBS) is an effective autonomic neuromodulation therapy. We aim to investigate the effects of CBS on hypoxia-induced pulmonary hypertension and its underlying mechanisms.</p><p><strong>Methods and results: </strong>Rats were randomly assigned into 4 groups, including a Control-sham group (n=7), a Control-CBS group (n=7), a Hypoxia-sham group (n=10) and a Hypoxia-CBS group (n=10). Echocardiography, ECG, and hemodynamics examination were performed. Samples of blood, lung tissue, pulmonary arteries, and right ventricle were collected for the further analysis. In the in vivo study, CBS reduced wall thickness and muscularization degree in pulmonary arterioles, thereby improving pulmonary hemodynamics. Right ventricle hypertrophy, fibrosis and dysfunction were all improved. CBS rebalanced autonomic tone and reduced the density of sympathetic nerves around pulmonary artery trunks and bifurcations. RNA-seq analysis identified <i>BDNF</i> and periostin (<i>POSTN</i>) as key genes involved in hypoxia-induced pulmonary hypertension, and CBS downregulated the mRNA expression of <i>BDNF</i> and <i>POSTN</i> in rat pulmonary arteries. In the in vitro study, norepinephrine was found to promote pulmonary artery smooth muscle cell proliferation while upregulating <i>BDNF</i> and <i>POSTN</i> expression. The proliferative effect was alleviated by silence <i>BDNF</i> or <i>POSTN</i>.</p><p><strong>Conclusions: </strong>Our results showed that CBS could rebalance autonomic tone, inhibit pulmonary arterial remodeling, and improve pulmonary hemodynamics and right ventricle function, thus delaying hypoxia-induced pulmonary hypertension progression. There may be a reciprocal interaction between <i>POSTN</i> and <i>BDNF</i> that is responsible for the underlying mechanism.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Carotid Baroreceptor Stimulation Ameliorates Pulmonary Arterial Remodeling in Rats With Hypoxia-Induced Pulmonary Hypertension.\",\"authors\":\"Xuesheng Fang, Jie Chen, Zhiling Hu, Ling Shu, Jing Wang, Mingyan Dai, Tuantuan Tan, Junxia Zhang, Mingwei Bao\",\"doi\":\"10.1161/JAHA.124.035868\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Sympathetic hyperactivity plays an important role in the initiation and maintenance of pulmonary hypertension. Carotid baroreceptor stimulation (CBS) is an effective autonomic neuromodulation therapy. We aim to investigate the effects of CBS on hypoxia-induced pulmonary hypertension and its underlying mechanisms.</p><p><strong>Methods and results: </strong>Rats were randomly assigned into 4 groups, including a Control-sham group (n=7), a Control-CBS group (n=7), a Hypoxia-sham group (n=10) and a Hypoxia-CBS group (n=10). Echocardiography, ECG, and hemodynamics examination were performed. Samples of blood, lung tissue, pulmonary arteries, and right ventricle were collected for the further analysis. In the in vivo study, CBS reduced wall thickness and muscularization degree in pulmonary arterioles, thereby improving pulmonary hemodynamics. Right ventricle hypertrophy, fibrosis and dysfunction were all improved. CBS rebalanced autonomic tone and reduced the density of sympathetic nerves around pulmonary artery trunks and bifurcations. RNA-seq analysis identified <i>BDNF</i> and periostin (<i>POSTN</i>) as key genes involved in hypoxia-induced pulmonary hypertension, and CBS downregulated the mRNA expression of <i>BDNF</i> and <i>POSTN</i> in rat pulmonary arteries. In the in vitro study, norepinephrine was found to promote pulmonary artery smooth muscle cell proliferation while upregulating <i>BDNF</i> and <i>POSTN</i> expression. The proliferative effect was alleviated by silence <i>BDNF</i> or <i>POSTN</i>.</p><p><strong>Conclusions: </strong>Our results showed that CBS could rebalance autonomic tone, inhibit pulmonary arterial remodeling, and improve pulmonary hemodynamics and right ventricle function, thus delaying hypoxia-induced pulmonary hypertension progression. There may be a reciprocal interaction between <i>POSTN</i> and <i>BDNF</i> that is responsible for the underlying mechanism.</p>\",\"PeriodicalId\":54370,\"journal\":{\"name\":\"Journal of the American Heart Association\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the American Heart Association\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/JAHA.124.035868\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Heart Association","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/JAHA.124.035868","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Carotid Baroreceptor Stimulation Ameliorates Pulmonary Arterial Remodeling in Rats With Hypoxia-Induced Pulmonary Hypertension.
Background: Sympathetic hyperactivity plays an important role in the initiation and maintenance of pulmonary hypertension. Carotid baroreceptor stimulation (CBS) is an effective autonomic neuromodulation therapy. We aim to investigate the effects of CBS on hypoxia-induced pulmonary hypertension and its underlying mechanisms.
Methods and results: Rats were randomly assigned into 4 groups, including a Control-sham group (n=7), a Control-CBS group (n=7), a Hypoxia-sham group (n=10) and a Hypoxia-CBS group (n=10). Echocardiography, ECG, and hemodynamics examination were performed. Samples of blood, lung tissue, pulmonary arteries, and right ventricle were collected for the further analysis. In the in vivo study, CBS reduced wall thickness and muscularization degree in pulmonary arterioles, thereby improving pulmonary hemodynamics. Right ventricle hypertrophy, fibrosis and dysfunction were all improved. CBS rebalanced autonomic tone and reduced the density of sympathetic nerves around pulmonary artery trunks and bifurcations. RNA-seq analysis identified BDNF and periostin (POSTN) as key genes involved in hypoxia-induced pulmonary hypertension, and CBS downregulated the mRNA expression of BDNF and POSTN in rat pulmonary arteries. In the in vitro study, norepinephrine was found to promote pulmonary artery smooth muscle cell proliferation while upregulating BDNF and POSTN expression. The proliferative effect was alleviated by silence BDNF or POSTN.
Conclusions: Our results showed that CBS could rebalance autonomic tone, inhibit pulmonary arterial remodeling, and improve pulmonary hemodynamics and right ventricle function, thus delaying hypoxia-induced pulmonary hypertension progression. There may be a reciprocal interaction between POSTN and BDNF that is responsible for the underlying mechanism.
期刊介绍:
As an Open Access journal, JAHA - Journal of the American Heart Association is rapidly and freely available, accelerating the translation of strong science into effective practice.
JAHA is an authoritative, peer-reviewed Open Access journal focusing on cardiovascular and cerebrovascular disease. JAHA provides a global forum for basic and clinical research and timely reviews on cardiovascular disease and stroke. As an Open Access journal, its content is free on publication to read, download, and share, accelerating the translation of strong science into effective practice.