Aneurysm-type Plexiform Lesions Form in Supernumerary Arteries in Pulmonary Arterial Hypertension: Potential Therapeutic Implications.

This study investigates the hypothesis that aneurysm-type plexiform lesions form in supernumerary arteries due to their anatomical properties and endothelial characteristics similar to PMVECs. To induce PAH, rats were injected with Sugen 5416, and exposed to hypoxia (10% O2) for 3 days (early-stage) or 3 weeks (mid-stage), or 3 weeks of hypoxia with an additional 10 weeks of normoxia (late-stage PAH). We examined morphology of pulmonary vasculature and vascular remodeling in lung serial sections from PAH and normal rats. Aneurysm-type plexiform lesions formed in small side branches of pulmonary arteries with morphological characteristics similar to supernumerary arteries. Over the course of PAH development, the number of Ki67-positive cells increased in small pulmonary arteries, including supernumerary arteries, while the number stayed consistently low in large pulmonary arteries. The increase in Ki67-positive cells was delayed in supernumerary arteries compared to small pulmonary arteries. In late-stage PAH, approximately 90% of small unconventional side branches that were likely to be supernumerary arteries were nearly closed. These results support our hypothesis that supernumerary arteries are the predominant site for aneurysm-type plexiform lesions in Sugen5416/hypoxia/normoxia-exposed PAH rats due partly to the combination of their unique anatomical properties and the hyper-proliferative potential of endothelial cells. We propose that the delayed and extensive occlusive ...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research