Novel Rat Model Paves the Way to Advance COPD-Associated Cor Pulmonale Research

Researchers have developed a novel rat model that closely replicates the pathological features and physiological changes associated with human chronic obstructive pulmonary disease (COPD)-associated cor pulmonale. This model exhibits key characteristics, including chronic lung inflammation, pulmonary hypertension, and right ventricular hypertrophy. The new study in The American Journal of Pathology, published by Elsevier, details the potential for the model to unravel the complex interactions between lung and heart pathology and improve patient outcomes.

COPD is a common chronic respiratory disease characterized by persistent respiratory symptoms and airflow limitation. The World Health Organization has ranked COPD as the third leading cause of mortality globally, with approximately 3.23 million deaths attributed to the disease in 2019. Approximately 6% of COPD patients develop cor pulmonale each year, which is a dysfunction of the right ventricle resulting from pulmonary disease and significantly deteriorates the prognosis of COPD. Cor pulmonale not only increases mortality among patients but also imposes a substantial economic burden on society. However, progress in related therapeutic research has been hampered by the lack of animal models that accurately simulate the complex interactions between COPD and cor pulmonale.

Lead investigator Tao Wang, MD, PhD, State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University, China, says, "The prognosis for individuals with COPD complicated by cor pulmonale is generally poor, and the existing treatment options are inadequate. To address the urgent need for a more accurate animal model of COPD-associated cor pulmonale, we were dedicated to developing a novel rat model to better emulate the human disease, providing valuable tools for future research and therapeutic development."

The researchers employed a comprehensive approach to developing and characterizing a novel rat model of COPD-associated cor pulmonale. The disease state was induced by combining chronic cigarette smoke exposure with left pulmonary artery ligation, followed by rigorous physiological, histological, and molecular analyses. The results demonstrated that this model recapitulated the pulmonary dysfunction, emphysema, and inflammatory infiltration characteristic of COPD. In addition, it also reproduced key features of cor pulmonale, including right ventricular hypertrophy, fibrosis, capillary rarefaction, and hemodynamic changes associated with pulmonary hypertension. Also, the investigators identified that pathways involving inflammation and oxidative stress may play significant roles in disease progression, highlighting their potential as therapeutic targets.

Co-lead investigator Lingdan Chen, MD, State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University, China, notes, "The development of this novel rat model represents a significant step forward in our ability to study COPD-associated cor pulmonale. By elucidating the underlying mechanisms of the disease and developing more effective therapeutic strategies, it provides an essential tool for overcoming the therapeutic challenges posed by this condition."

This model is expected to facilitate the discovery of novel molecular insights and the identification of innovative therapeutic targets.

Co-investigators Zhuoji Ma, MSc, State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University, China, and Suiyang Tong, PhD, Department of Cardiology, Suizhou Hospital, Hubei University of Medicine, China, conclude, "We are excited about the potential of this model to accelerate the discovery of new therapeutic strategies, which are desperately needed for patients with COPD-associated cor pulmonale."

Notes for editors

The article is “Development and Characterization of a Novel Rat Model for Emulating Chronic Obstructive Pulmonary Disease—Associated Cor Pulmonale,” by Zhuoji Ma, Suiyang Tong, Yuhang Huang, Neng Wang, Guanjin Chen, Qianwen Bai, Jia Deng, Liang Zhou, Qiao Luo, Jian Wang, Wenju Lu, Lingdan Chen, and Tao Wang (https://doi.org/10.1016/j.ajpath.2025.01.003). It appears in The American Journal of Pathology, volume 195, issue 5 (May 2025), published by Elsevier.

The article is openly available at https://ajp.amjpathol.org/article/S0002-9440(25)00034-3/fulltext.

Full text of the article is also available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 406 1313 or [email protected] to request a PDF of the article or more information. To reach the study’s authors, contact Tao Wang, MD, PhD, at [email protected].

This work was supported by grants from the National Natural Science Foundation of China (82270053 and 82241024), Guangdong Outstanding Young Scientist Funding (2021B1515020006), the Science and Technology Program of Guangzhou, China (SL2024A04J01572 and SL2023A03J01309), R&D Program of Guangzhou National Laboratory (grant GZNL2023A02013), and Hubei Provincial Key Research and Development Program (Health Care Field Supporting Local Special Projects; 2022BCE053).

About The American Journal of Pathology

The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches. ajp.amjpathol.org

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