Michel R Corboz, Tam L Nguyen, Andy Stautberg, David Cipolla, Walter R Perkins, Richard W Chapman
{"title":"糖/缺氧诱导大鼠肺动脉高压的生物学和药理学现状概览》(Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.","authors":"Michel R Corboz, Tam L Nguyen, Andy Stautberg, David Cipolla, Walter R Perkins, Richard W Chapman","doi":"10.1089/jamp.2024.0016","DOIUrl":null,"url":null,"abstract":"<p><p>The Sugen 5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) demonstrates most of the distinguishing features of PAH in humans, including increased wall thickness and obstruction of the small pulmonary arteries along with plexiform lesion formation. Recently, significant advancement has been made describing the epidemiology, genomics, biochemistry, physiology, and pharmacology in Su/Hx challenge in rats. For example, there are differences in the overall reactivity to Su/Hx challenge in different rat strains and only female rats respond to estrogen treatments. These conditions are also encountered in human subjects with PAH. Also, there is a good translation in both the biochemical and metabolic pathways in the pulmonary vasculature and right heart between Su/Hx rats and humans, particularly during the transition from the adaptive to the nonadaptive phase of right heart failure. Noninvasive techniques such as echocardiography and magnetic resonance imaging have recently been used to evaluate the progression of the pulmonary vascular and cardiac hemodynamics, which are important parameters to monitor the efficacy of drug treatment over time. From a pharmacological perspective, most of the compounds approved clinically for the treatment of PAH are efficacious in Su/Hx rats. Several compounds that show efficacy in Su/Hx rats have advanced into phase II/phase III studies in humans with positive results. Results from these drug trials, if successful, will provide additional treatment options for patients with PAH and will also further validate the excellent translation that currently exists between Su/Hx rats and the human PAH condition.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"37 5","pages":"241-283"},"PeriodicalIF":2.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502635/pdf/","citationCount":"0","resultStr":"{\"title\":\"Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.\",\"authors\":\"Michel R Corboz, Tam L Nguyen, Andy Stautberg, David Cipolla, Walter R Perkins, Richard W Chapman\",\"doi\":\"10.1089/jamp.2024.0016\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The Sugen 5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) demonstrates most of the distinguishing features of PAH in humans, including increased wall thickness and obstruction of the small pulmonary arteries along with plexiform lesion formation. Recently, significant advancement has been made describing the epidemiology, genomics, biochemistry, physiology, and pharmacology in Su/Hx challenge in rats. For example, there are differences in the overall reactivity to Su/Hx challenge in different rat strains and only female rats respond to estrogen treatments. These conditions are also encountered in human subjects with PAH. Also, there is a good translation in both the biochemical and metabolic pathways in the pulmonary vasculature and right heart between Su/Hx rats and humans, particularly during the transition from the adaptive to the nonadaptive phase of right heart failure. Noninvasive techniques such as echocardiography and magnetic resonance imaging have recently been used to evaluate the progression of the pulmonary vascular and cardiac hemodynamics, which are important parameters to monitor the efficacy of drug treatment over time. From a pharmacological perspective, most of the compounds approved clinically for the treatment of PAH are efficacious in Su/Hx rats. Several compounds that show efficacy in Su/Hx rats have advanced into phase II/phase III studies in humans with positive results. Results from these drug trials, if successful, will provide additional treatment options for patients with PAH and will also further validate the excellent translation that currently exists between Su/Hx rats and the human PAH condition.</p>\",\"PeriodicalId\":14940,\"journal\":{\"name\":\"Journal of Aerosol Medicine and Pulmonary Drug Delivery\",\"volume\":\"37 5\",\"pages\":\"241-283\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502635/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Aerosol Medicine and Pulmonary Drug Delivery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/jamp.2024.0016\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jamp.2024.0016","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.
The Sugen 5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) demonstrates most of the distinguishing features of PAH in humans, including increased wall thickness and obstruction of the small pulmonary arteries along with plexiform lesion formation. Recently, significant advancement has been made describing the epidemiology, genomics, biochemistry, physiology, and pharmacology in Su/Hx challenge in rats. For example, there are differences in the overall reactivity to Su/Hx challenge in different rat strains and only female rats respond to estrogen treatments. These conditions are also encountered in human subjects with PAH. Also, there is a good translation in both the biochemical and metabolic pathways in the pulmonary vasculature and right heart between Su/Hx rats and humans, particularly during the transition from the adaptive to the nonadaptive phase of right heart failure. Noninvasive techniques such as echocardiography and magnetic resonance imaging have recently been used to evaluate the progression of the pulmonary vascular and cardiac hemodynamics, which are important parameters to monitor the efficacy of drug treatment over time. From a pharmacological perspective, most of the compounds approved clinically for the treatment of PAH are efficacious in Su/Hx rats. Several compounds that show efficacy in Su/Hx rats have advanced into phase II/phase III studies in humans with positive results. Results from these drug trials, if successful, will provide additional treatment options for patients with PAH and will also further validate the excellent translation that currently exists between Su/Hx rats and the human PAH condition.
期刊介绍:
Journal of Aerosol Medicine and Pulmonary Drug Delivery is the only peer-reviewed journal delivering innovative, authoritative coverage of the health effects of inhaled aerosols and delivery of drugs through the pulmonary system. The Journal is a forum for leading experts, addressing novel topics such as aerosolized chemotherapy, aerosolized vaccines, methods to determine toxicities, and delivery of aerosolized drugs in the intubated patient.
Journal of Aerosol Medicine and Pulmonary Drug Delivery coverage includes:
Pulmonary drug delivery
Airway reactivity and asthma treatment
Inhalation of particles and gases in the respiratory tract
Toxic effects of inhaled agents
Aerosols as tools for studying basic physiologic phenomena.