Premium
Modulating heme biosynthesis, through the administration of exogenous aminolevulinic acid may attenuate monocrotaline induced‐pulmonary arterial hypertension
Author(s) -
Alhawaj Raed,
Ghadhanfar Elham,
Cherian Susan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1016.15
Subject(s) - heme , oxidative stress , reactive oxygen species , pulmonary hypertension , vasoconstriction , chemistry , right ventricular hypertrophy , biosynthesis , pharmacology , medicine , biochemistry , enzyme
Pulmonary arterial hypertension (PAH) is a progressive disease that initiates in small pulmonary arteries and arterioles, which undergo persistent vasoconstriction and vascular remodeling. This process elevates vascular resistance, pulmonary arterial pressure and ultimately results in right heart hypertrophy and failure. PAH can be induced in rats through exposure to the pneumotoxin monocrotaline (MCT). Deregulation of heme biosynthesis, which might accompany/contribute to elevated mitochondrial/cytosolic reactive oxygen species (ROS) is thought to propagate MCT‐induced PAH disease process. Elevated oxidative stress can augment the redox‐sensitive proto‐oncogene c‐Src kinase in PASMCs and thus might drive vascular remodeling further through the (c‐Src‐STAT3) axis. By administering the biosynthetic precursor of heme, aminolevulinic acid (ALA), we aim to drive heme biosynthesis and probably attenuate oxidative stress‐induced c‐Src activation.