A team led by researchers at School of Pharmacy, Hampton University in Virginia recently discovered new key players in pulmonary fibrosis development and related angiogenesis. The study was published in the Journal of Cellular Biochemistry and is entitled “Nitric Oxide Mediates Bleomycin-Induced Angiogenesis and Pulmonary Fibrosis via Regulation of VEGF.”
Pulmonary fibrosis is a progressive fatal lung disease in which the lung tissues and alveoli are damaged, becoming thick and scarred (fibrosis), leading to severe breathing difficulties and compromising oxygen transfer between the lungs and the bloodstream. The disease is characterized by a rapid growth of fibrous tissue and increased angiogenesis (formation of new blood vessels). Pulmonary fibrosis has a poor prognosis and respiratory failure is the main cause of death associated with the disease.
Pulmonary fibrosis has been linked to a dysfunction in angiogenic mediators, although their role remains poorly understood. The vascular endothelial growth factor (VEGF) has been reported to be deregulated in patients with fibrotic diseases. This factor plays an important role in angiogenesis and vascular permeability being expressed in several types of cells in the human lungs. High expression of other angiogenic mediators, like plasminogen activator inhibitor-1 (PAI-1) and cytokines such as interleukin-8 (IL-8) have also been associated to pulmonary fibrosis. Free radicals like nitric oxide (NO) are also known to have an important role in pulmonary fibrosis development.
In the study, researchers analyzed the role of angiogenesis in pulmonary fibrosis pathogenesis and the effects of angiogenic mediators like VEGF and NO in disease development. The team used a mouse model where pulmonary fibrosis was induced by bleomycin (an antitumor antibiotic).
Researchers found that treatment with bleomycin promotes angiogenesis and induces the production of NO, which in turn, was found to be a key regulator of the angiogenic mediator VEFG. Other important angiogenic proteins like PAI-1 and IL-8 were found to be regulated by VEFG. VEFG inhibition of by CBO-P11 (an anti-VEGF antibody) and of NO significantly attenuated bleomycin-induced pulmonary fibrosis in mice through a mitigation of the induced angiogenic and fibrogenic responses.
The research team concluded that both VEGF and NO are key players in the response to bleomycin-induced pulmonary fibrosis and related angiogenesis. The team proposes that VEGF and NO could be exploited as potential therapeutic targets for this serious disease.