Micromanaging vascular biology: tiny microRNAs play big band.
Micro-RNAs (miRNAs) are estimated to regulate 30% of the human genome primarily through translational repression. In 2005-2008, the first series of observations establishing the key significance of miRNAs in the regulation of vascular biology came from experimental studies involved in arresting miRNA biogenesis to deplete the miRNA pools of vascular tissues and cells. Dicer-dependent biogenesis of miRNA is required for blood vessel development during embryogenesis and wound healing. miRNAs regulate redox signaling in endothelial cells, a key regulator of vascular cell biology. miRNAs that regulate angiogenesis include miRNA 17-5p, cluster 17-92, 21, 27a&b, 126, 130a, 210, 221, 222, 378 and the let7 family. miRNAs also represent a new therapeutic target for the treatment of proliferative vascular diseases as well as hypertension. Evidence supporting the regulation of inducible adhesion molecules by miRNA supports a role of miRNAs in regulating vascular inflammation. Productive strategies to safely up-regulate as well as down-regulate miRNAs in vivo are in place and being tested for their value in disease intervention. Prudent targeting of non-coding genes such as miRNAs, which in turn regulates large sets of coding genes, holds promise in gene therapy. Recent developments in miRNA biology offer lucrative opportunities to manage vascular health.
Sen
Chandan K
CK
Laboratory of Molecular Medicine, Department of Surgery, Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio 43210, USA. chandan.sen@osumc.edu
Gordillo
Gayle M
GM
Khanna
Savita
S
Roy
Sashwati
S
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D005810:Multigene Family; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism; D014652:Vascular Diseases / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D014945:Wound Healing / Q000235:genetics
D035683:MicroRNAs