Heme Biosynthesis Modulation via δ-Aminolevulinic Acid Administration

Abstract 24 This study examines how heme biosynthesis modulation with δ-aminolevulinic 25 acid (ALA) potentially functions to prevent 21-day hypoxia (10% oxygen)-induced 26 pulmonary hypertension in mice and the effects of 24 hour organoid culture with 27 bovine pulmonary arteries (BPA) with the hypoxia and pulmonary hypertension 28 mediator endothelin-1 (ET-1), with a focus on changes in superoxide and 29 regulation of miR204 expression by src kinase phosphorylation of STAT3. The 30 treatment of mice with ALA attenuated pulmonary hypertension (assessed 31 through echo Doppler flow of the pulmonary valve, and direct measurements of 32 right ventricular systolic pressure and right ventricular hypertrophy), increases in 33 pulmonary arterial superoxide (detected by lucigenin), and decreases in lung 34 miR204 and mitochondrial SOD2 expression. ALA treatment of BPA attenuated 35 ET-1 induced increases in mitochondrial superoxide (detected by MitoSox), 36