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Fig. 7 | Biology of Sex Differences

Fig. 7

From: Early progression of pulmonary hypertension in the monocrotaline model in males is associated with increased lung permeability

Fig. 7

Overall mechanisms of heme-induced barrier dysfunction. During hemolysis, hemoglobin releases its co-factor, free heme. Through the heme carrier protein 1 (HCP1), free heme translocates into cells, leading to the activation of heme oxygenase and barrier disruptive mechanisms. Heme affects the barrier in two phases. First, heme induces actin fibers formation by upregulation of HSP27, inactivation of barrier protective MYPT and Rac1, leading to increased phosphorylation of MLC. The second phase is the dysregulation of tight junctions (TJ) between cells resulting in fluid leakage through the endothelial barrier. These effects of free heme contribute to the development of pulmonary hypertension via inflammation, vasoconstriction and local hypoxia due to the formation of perivascular cuffs

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