title: Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling.
abstract: A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role. The miR-221/222 cluster controls development and differentiation of ECs but inhibits their proangiogenic activation, proliferation, and migration. miR-221/222 are primarily implicated in maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular expression of miR-221/222 is upregulated in initial atherogenic stages causing inhibition of angiogenic recruitment of ECs and increasing endothelial dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and switching from the VSMC "contractile" phenotype to the "synthetic" phenotype associated with induction of proliferation and motility. In atherosclerotic vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation downregulates miR-221/222 expression in ECs that in turn could activate intralesion neoangiogenesis. In addition, both miRNAs could contribute to cardiovascular pathology through their effects on fat and glucose metabolism in nonvascular tissues such as adipose tissue, liver, and skeletal muscles.
authors.affiliation: Department of Medical Nanobiotechnology, Pirogov Russian State Medical University, Moscow 117997, Russia ; The Mount Sinai Community Clinical Oncology Program, Mount Sinai Comprehensive Cancer Center, Mount Sinai Medical Center, Miami Beach, FL 33140, USA.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Chistiakov
authors.affiliation: Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow 125315, Russia ; Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow 121552, Russia.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Sobenin
authors.affiliation: Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow 125315, Russia ; Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow 121609, Russia.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Orekhov
authors.affiliation: Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow 125315, Russia ; Faculty of Medicine and St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, NSW 2052, Australia ; School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
mesh_terms: D050197:Atherosclerosis / Q000235:genetics* / Q000503:physiopathology*; D001483:Base Sequence; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012307:Risk Factors; D066253:Vascular Remodeling / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C525709:MIR221, human; C525710:MIR222, human