microRNAs in Cerebrovascular Disease

Abstract

Cardiovascular diseases are major causes of morbidity and mortality in developed countries. Cerebrovascular diseases, especially stroke, represent major burden of disability and economy impact. Major advances in primary and secondary prevention and therapy are needed in order to tackle this public health problem. Our better understanding of pathophysiology is essential in order to develop novel diagnostic and therapeutic tools and strategies. microRNAs are a family of important post-transcriptional regulators of gene expression and their involvement in the pathophysiology of cerebrovascular diseases has already been reported. Moreover, microRNAs may represent above-mentioned potential diagnostic and therapeutic tools in clinical practice. Within this chapter, we briefly describe basic epidemiology, aetiology and clinical manifestation of following cerebrovascular diseases: extracranial carotid atherosclerosis, acute stroke, intracranial aneurysms and cerebral arterio-venous malformations. Further, in each chapter, the current knowledge about the involvement of specific microRNAs and their potential use in clinical practice will be summarized. More specifically, within the subchapter "miRNAs in carotid atherosclerosis", general information about miRNA involvement in atherosclerosis will be described (miR-126, miR-17-92, miR-155 and others) with special emphasis put on miRNAs affecting carotid plaque progression and stability (e.g. miR-145, miR-146 or miR-217). In the subchapter "miRNAs in acute stroke", we will provide insight into recent knowledge from animal and human studies concerning miRNA profiling in acute stroke and their expression dynamics in brain tissue and extracellular fluids (roles of, e.g. let-7 family, miR-21, miR-29 family, miR-124, miR-145, miR-181 family, miR-210 and miR-223). Subchapters dealing with "miRNAs and AV malformations" and "miRNAs and intracranial aneurysms" will focus on miR-21, miR-26, miR-29 family and miR-143/145.

Association between functional polymorphisms in the promoter of the miR-143/145 cluster and risk of intracranial aneurysm

“…A notable example is the miR-143/145 cluster, which is strongly expressed in SMCs, acting as an anti-atherosclerotic in a paracrine manner2728293031. miR-143 and miR-145 have been shown to be protective during vascular remodelling and carotid plaque progression and stabilization323334. In miR-143/145-null mice, vascular SMCs are locked in the synthetic state that favor neointimal lesion development28.…”

Cardiovascular consequences of metabolic syndrome

“…These methods can provide powerful integrative insights into whole-body, tissue, and/or cellular physiology, but at the cost of producing a large number of inter-related results that can be challenging to interpret. Associations between select miR species and specific cardiovascular disease, along with associations with putative mechanistic mediators, have been observed for atrial fibrillation (198), and cerebrovascular disease (199), along with associations with pathophysiologic mediators of vascular disease including lipid metabolism (200)and endothelial dysfunction (201). A comprehensive review of the current state of knowledge linking miR and cardiovascular disease has recently been published (202).…”

MicroRNA: A new therapeutic strategy for cardiovascular diseases

“…Antagomirs are also served as potential tools for preventing cancer [85] and therefore, could be used in the clinical practice to repress tumor growth. Moreover, the use of anti-sense miRNA treatment is an important strategy to overcome other pathological states like spinal cord injury [71] and ischemic stroke [92]. Thus, RNA mimics and inhibitors are useful in identifying and confirming the pairs of miRNA/target genes that are predicted by computational tools.…”