Non-coding RNAs in cerebral endothelial pathophysiology: emerging roles in stroke.
Cerebral vascular endothelial cells form the major element of the blood-brain barrier (BBB) and constitute the primary interface between circulating blood and brain parenchyma. The structural and functional changes in cerebral endothelium during cerebral ischemia are well known to result in BBB disruption, vascular inflammation, edema, and angiogenesis. These complex pathological processes directly contribute to brain infarction, neurological deficits, and post-stroke neurovascular remodeling. Ischemic endothelial dysfunction appears to be tightly controlled by multiple gene signaling networks. Non-coding RNAs (ncRNAs) are functional RNA molecules that are generally not translated into proteins but can actively regulate the expression and function of many thousands of protein-coding genes by different mechanisms. Various classes of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), small nucleolar RNAs (snoRNAs) and piwi-interacting RNAs (piRNAs), are highly expressed in the cerebrovascular endothelium where they serve as critical mediators to maintain normal cerebral vascular functions. Dysregulation of ncRNA activities has been closely linked to the pathophysiology of cerebral vascular endothelium and neurologic functional disorders in the brain's response to ischemic stimuli. In this review, we summarize recent advancements of these ncRNA mediators in the brain vasculature, highlighting the specific roles of endothelial miRNAs in stroke.
Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Electronic address: kejie@med.umich.edu.
Ke-Jie
KJ
Yin
Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue SL83, New Orleans, LA 70112, USA.
Milton
M
Hamblin
Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Y Eugene
YE
Chen
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D022661:RNA, Untranslated / Q000235:genetics*; D020521:Stroke / Q000503:physiopathology*
D022661:RNA, Untranslated
Angiogenesis; Blood–brain barrier; Cerebral vascular endothelial cells; Ischemic stroke; Non-coding RNAs; microRNA