PDT Targeting Pulmonary Hypertension: Implications Prevention and Treatment by Photodynamic Therapy

Purpose Pulmonary arterial hypertension (PH) is an unremitting disease defined by progressive increase in pulmonary vascular resistance and vascular remodeling. Currently, little is known about treatments that affect vascular endothelial cell related pathogenic feature of PH. We propose to use photodynamic therapy (PDT) to treat PH, which use vascular specific light sensitive drug (a photosensitizer) and light in the presence of oxygen to irreversibly damage cells. We hypothesize that PDT can reverse vascular remodeling in PH through anti-endothelial proliferative mechanisms. Aim of this study therefore is to evaluate the therapeutic effects of PDT using animal PH model. Methods and Materials To induce PH, Sprague Dawley rats were injected with 60mg/kg monocrotaline (MCT). At day 7, PDT (630nm, 50 J/cm 2 ) using the photosensitizer, aminolevulinic acid (ALA) was administered. Hemodynamic measurements were taken on day 21 and lung and heart samples were dissected for molecular protein analysis. Results Rats treated with PDT using ALA had a significant reduction in right ventricular systolic pressure (RVSP), implying lower pulmonary arterial pressure, and a decreased ratio of RV/LV+S (right ventricle/left ventricle + septum), signifying reduced RV hypertrophy, compared with MCT-PH rats that received solely laser treatment. We observed a significant increase in P21Cip expression and decreased CKD1 and PCNA expression in the rat receiving PDT treatment. Hematoxylin and immunostaining showed PDT partially reverse MCT induced vascular remodeling in the lung treated versus untreated rats. Conclusions The clinical relevance of the findings in animal models will be assessed in human PAH lung tissue after lung transplantation. With these studies, we hope to provide new approaches for the treatment of this devastating disease.