Pluripotent hematopoietic stem cells augment (cid:2) -adrenergic receptor-mediated contraction of pulmonary artery and contribute to the pathogenesis of pulmonary hypertension

Pluripotent hematopoietic stem cells augment (cid:2) -adrener-gic receptor-mediated contraction of pulmonary artery and contribute to the pathogenesis of pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 318: hypertension (PH) is a multicellular and progressive disease with a high mortality rate. Among many cell types, hematopoietic stem cells (HSCs) are incriminated in the pathogenesis of PH. However, our understanding of the mechanisms that increase HSCs in blood and lungs of hypertensive animals or patients and the role played by HSCs in the mice. Furthermore, knockdown of G6PD and inhibition of G6PD activity: 1 ) downregulated canonical and noncanonical Wnt and Fzd receptors genes; 2 ) upregulated Bmpr1a ; 3 ) decreased Cxcl12 , and 4 ) reduced HSC (CD117 (cid:3) and CD133 (cid:3) ) numbers. In all, our findings demonstrate unexpected function for bone marrow-derived HSCs in aug- menting (cid:2) -adrenergic receptor-mediated contraction of pulmonary arteries and remodeling of pulmonary arteries that contribute to increase pulmonary vascular resistance in PAH patients and hypoxic mice and suggest that G6PD, by regulating expression of genes in the WNT and BMPR signaling, contributed to increase and release of HSCs from the bone marrow in response to hypoxic stimuli.

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