%0 Journal Article
%T Distinct plasma gradients of microRNA
%A Akaya Smith
%A Anjali Vaidya
%A Annie Watson
%A Chad M. Kosanovich
%A Dmitry A. Goncharov
%A Elena A. Goncharova
%A Jeremy Mazurek
%A John C. Sembrat
%A Leonard E. Estephan
%A Marc A. Simon
%A Mauricio Rojas
%A Michael G. Risbano
%A Michael V. Genuardi
%A Nancy Petro
%A Stephen Y. Chan
%A Yassmin Al Aaraj
%A Yingze Zhang
%A Yuchi Han
%J Pulmonary Circulation
%@ 2045-8940
%D 2019
%R 10.1177/2045894019840646
%X Pulmonary hypertension (PH), a heterogeneous vascular disease, consists of subtypes with overlapping clinical phenotypes. MicroRNAs, small non-coding RNAs that negatively regulate gene expression, have emerged as regulators of PH pathogenesis. The muscle-specific micro RNA (miR)-204 is known to be depleted in diseased pulmonary artery smooth muscle cells (PASMCs), furthering proliferation and promoting PH. Alterations of circulating plasma miR-204 across the trans-pulmonary vascular bed might provide mechanistic insights into the observed intracellular depletion and may help distinguish PH subtypes. MiR-204 levels were quantified at sequential pulmonary vasculature sites in 91 patients with World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH) (n£¿=£¿47), Group II PH (n£¿=£¿22), or no PH (n£¿=£¿22). Blood from the right atrium/superior vena cava, pulmonary artery, and pulmonary capillary wedge was collected. Peripheral blood mononuclear cells (PBMCs) were isolated (n£¿=£¿5/group). Excretion of miR-204 by PAH-PASMCs was also quantified in vitro. In Group I patients only, miR-204 concentration increased sequentially along the pulmonary vasculature (log fold-change slope£¿=£¿0.22 [95% CI£¿=£¿0.06¨C0.37], P£¿=£¿0.008). PBMCs revealed insignificant miR-204 variations among PH groups (P£¿=£¿0.12). Cultured PAH-PAMSCs displayed a decrease of intracellular miR-204 (P£¿=£¿0.0004), and a converse increase of extracellular miR-204 (P£¿=£¿0.0018) versus control. The stepwise elevation of circulating miR-204 across the pulmonary vasculature in Group I, but not Group II, PH indicates differences in muscle-specific pathobiology between subtypes. Considering the known importance of miR-204 in PH, these findings may suggest pathologic excretion of miR-204 in Group I PAH by PASMCs, thereby accounting for decreased intracellular miR-204 concentration
%K circulating microRNA
%K pulmonary hypertension
%K biomarker
%K heart failure
%U https://journals.sagepub.com/doi/full/10.1177/2045894019840646