Microparticles stimulated by hypoxic pulmonary hypertension have differing effects on vascular cell growth than microparticles from severe occlusive pulmonary arterial hypertension (1090.7)

Abstract

The release of microparticles (MPs), intact, sub‐micron vesicles containing signaling molecules such as proteins, lipids, mRNAs, and miRNAs, is significantly increased in pulmonary arterial hypertension (PAH). MPs contribute to vascular cell proliferation, and the mechanism of increased proliferation in the arteriopathy of PAH is still unclear. Thus, we propose that circulating MPs from pulmonary hypertensive rats will stimulate pulmonary microvascular endothelial (PMVEC) and/or pulmonary artery smooth muscle cell (PASMC) proliferation. PMVECs and PASMCs were treated with MPs from controls, 3 wk hypoxia only (Hx) rats, or 3 wk Su/Hx/Nx rats. Interestingly, although the Su/Hx/Nx model shows severe vascular remodeling, MPs from the hypoxic rat had the most significant effects on PASMC proliferation by shifting the log phase of growth. Western blot analysis shows corresponding changes in smooth muscle cell markers. PMVECs were treated similarly with 5 wk MPs from the Su/Hx/Nx progressive model, resulting in a shift of log growth phase. Our data suggest that circulating MPs isolated from 3 wk Hx‐treated rats may signal to PASMCs to increase proliferation, whereas MPs from a severe occlusive model of PAH stimulate changes in proliferation rates of PMVECs. Combined these data suggest that hypoxic pulmonary hypertension and severe occlusive PAH result in different signaling MPs with unique vascular cell effects.Grant Funding Source: Supported by NHLBI T32 HL076125 to TMY and AHA 11SDG7390037 to NNB.