Pulmonary arterial hypertension and microRNAs--an ever-growing partnership.
Pulmonary arterial hypertension (PAH) is a debilitating condition with progressive remodeling of the pulmonary resistance vessels. PAH is characterized by multifocal, polyclonal lesions inhabited by cells that underwent phenotypic transition, resulting in altered cell proliferation and contractility, ultimately resulting in increased vascular resistance. Diagnosis of PAH is confounded by the fact that it is largely asymptomatic in the initial stages. In fact, idiopathic PAH patients >65 years of age cannot be diagnosed hemodynamically due to high pulmonary capillary wedge pressure. This highlights the need for defining more robust molecular biomarkers for PAH diagnosis and progression. Recent studies have indicated that microRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression, play a discrete role in vascular inflammation and in the etiology of cardiovascular pathologies inclusive of PAH and can potentially serve as diagnostic biomarkers. However, a cohesive understanding of global miRNA-mediated molecular events that control pulmonary vasculature plasticity is lacking which, if addressed systematically, can lead to detailed elucidation of the downstream cellular pathways that are affected by activation/silencing of silenced cognate transcripts. In turn, this can lead to not only robust biomarkers, but also to novel therapeutic strategies targeting more upstream regulators than the existing ones targeting more downstream effectors. The current review aims to provide a summary understanding of PAH, its associated pathophysiology, current knowledge of the role of miRNAs in PAH, and identifies grey areas that need further research for successful bench-to-bedside transition of these exciting new discoveries.
Department of Geriatric Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Yong
Y
Wang
Xin-ying
XY
Xue
Yu-xia
YX
Liu
Kai-fei
KF
Wang
Xue-feng
XF
Zang
Jing
J
Wang
Pei-lan
PL
Wang
Jie
J
Zhang
Lei
L
Pan
Shu-yang
SY
Zhang
Jian-xin
JX
Wang
D000368:Aged; D000818:Animals; D049109:Cell Proliferation; D018450:Disease Progression; D065627:Familial Primary Pulmonary Hypertension; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology
D035683:MicroRNAs
Hypertension; Pulmonary arterial hypertension; Pulmonary hypertension; Vascular remodeling; microRNAs