Pluripotent HSCs Augment a-Adrenergic Receptor-Mediated Contraction of Pulmonary Artery and Contribute to the Pathogenesis of Pulmonary Hypertension.

Pluripotent HSCs Augment a-Adrenergic Receptor-Mediated Contraction of Pulmonary Artery and Contribute to the Pathogenesis of Pulmonary Hypertension. Am J Physiol Lung Cell Mol Physiol. 2020 Jan 08;: Authors: Hashimoto R, Lanier GM, Dhagia V, Joshi S, Jordan A, Waddell I, Tuder RM, Stenmark KR, Wolin MS, McMurtry IF, Gupte SA Abstract Pulmonary hypertension (PH) is a multi-cellular disease with a high mortality rate. Amongst many cell-types, hematopoietic stem cells (HSCs) are incriminated in the pathogenesis of PH. However, our understanding of the mechanisms that increase HSCs in hypertensive animals or patients remains elusive. Studies suggest that glycolysis is critical for the growth of HSCs. In various cell-types from hypertensive lungs of animals and patients, glycolysis and the glucose-6-phosphate dehydrogenase (G6PD) activity are increased. Herein, we demonstrated in mice that hypoxia increased HSCs in bone marrow and blood, and around hypertensive pulmonary arteries (PA) in a time-dependent manner. Likewise, the numbers of HSCs in the blood of patients with pulmonary arterial hypertension (PAH) were higher (>3-fold) when compared to healthy individuals. By bone marrow transplantation, we found that GFP+bone marrow cells infiltrated the lungs and accumulated around the PA in hypoxic mice and these cells contributed to the increased a-adrenergic receptor (AR)-mediated contraction of the PA cultured in hypoxia. Inhibition o...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research