Figure 1: Cav1 deficiency induces pulmonary hypertension. In Cav1^-/- mice, Cav1 deficiency induces eNOS activation and ROS production to form peroxynitrite which modifies PKG through tyrosine nitration. PKG nitration impairs PKG activity and thereby induces pulmonary vasoconstriction and vascular remodeling leading to development of pulmonary hypertension. Increased eNOS activity and PKG nitration concomitant with decreased Cav1expression are observed in lung tissues from IPAH patients. Tissue hypoxia and inflammation may augment oxidative/nitrative stress and thereby PKG nitration. In addition, Cav1 deficiency activates STAT3. Tissue hypoxia and inflammation also results in STAT3 activation. Activated STAT3 induces vascular remodeling and thereby contributes to the pathogenesis of PH.