Related Experiment Video
Updated: May 22, 2025
Implantation of Fibrin Gel on Mouse Lung to Study Lung-specific Angiogenesis
Published on: December 21, 2014
Proline betaine facilitates angiogenesis in bronchopulmonary dysplasia
Wangdui Cili1, Zhiye Qi1, Qinghua Zhong1
1Department of Pediatrics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province 650032, China.
Insights
Proline betaine, a natural compound, promotes blood vessel growth and reduces lung damage in a model of bronchopulmonary dysplasia (BPD). This suggests its potential as a new treatment for BPD in infants.
Area of Science:
- Neonatal Medicine
- Pharmacology
- Pulmonary Biology
Background:
- Bronchopulmonary dysplasia (BPD) is a common and severe lung disease in preterm infants.
- It is characterized by abnormal lung development and significant morbidity.
- Current treatments for BPD are limited, highlighting the need for novel therapeutic strategies.
Purpose of the Study:
- To investigate the therapeutic potential of proline betaine in a preclinical model of BPD.
- To explore the mechanisms by which proline betaine may exert its effects on lung development and injury.
Main Methods:
- Network pharmacology was used to identify potential targets of proline betaine relevant to BPD.
- In vitro studies assessed proline betaine's effects on human umbilical vein endothelial cells (HUVECs) to evaluate proliferation and angiogenesis.
- An in vivo hyperoxia-induced BPD rat model was employed to assess pulmonary injury, angiogenesis, and fibrosis.
Main Results:
- Proline betaine demonstrated significant pro-angiogenic effects on HUVECs in vitro, enhancing tube formation and capillary length in a dose-dependent manner.
- In the BPD rat model, proline betaine treatment improved lung structure by increasing alveolarization and reducing collagen deposition.
- Mechanistically, proline betaine upregulated VEGF and VEGFR2 expression and activated the MEK/ERK pathway, which was crucial for its therapeutic effects.
Conclusions:
- Proline betaine effectively enhances angiogenesis and mitigates pulmonary injury in a BPD model.
- The therapeutic benefits are mediated through the MEK/ERK signaling pathway.
- Proline betaine shows promise as a novel therapeutic agent for managing bronchopulmonary dysplasia in neonates.
Background:
Bronchopulmonary dysplasia (BPD) is prevalent and severe diseases in preterm infants, characterized by abnormal lung development. This study aims to investigate the therapeutic potential of proline betaine, a natural alkaloid recognized for its vasculo-protective and anti-inflammatory properties, in BPD model.
Methods:
Network pharmacology was utilized to predict the targets of proline betaine and BPD-related genes (BPD-RGs). In vitro, HUVECs were treated with proline betaine to evaluate its effects on proliferation and angiogenesis. In vivo, a hyperoxia-induced BPD rat model (85 % oxygen, first day to 14th day) was used to evaluate the effects of proline betaine on pulmonary injury, angiogenesis and fibrosis.
Results:
We identified a total of 100 proline-betaine targets and 825 BPD-RGs, with 20 shared targets between them. These shared targets modulated inflammation, immune response, hypoxia, and vascular homeostasis, especially the vascular phenotype. In vitro, proline betaine significantly enhanced the activity, number of tubes, and capillary length of HUVECs. The pro-angiogenic effect of proline betaine on HUVECs was dose-dependent. The hyperoxia-induced BPD rat model corroborated these findings. In vivo, proline betaine increased the radial alveolar count and reduced the mean linear intercept and collagen content in the lung. Mechanistically, proline betaine upregulated VEGF and VEGFR2 expression as well as MEK/ERK pathway activity. Notably, blocking the VEGFR2 and MEK/ERK pathways made proline betaine less effective as a medicine.
Conclusion:
Proline betaine enhances angiogenesis and mitigates pulmonary injury through the MEK/ERK pathway. These findings suggest that proline betaine could serve as a novel therapeutic strategy for managing BPD in neonates.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:10Mechanism of Angiogenesis
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...