Novel rat model could 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 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 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 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.

“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,” conclude co-investigators Zhuoji Ma and Suiyang Tong.