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Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling.

Chistiakov DA, Sobenin IA, Orekhov AN, Bobryshev YV - Biomed Res Int (2015)

Bottom Line: 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).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 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Biogenesis of human miR-221/222. miRNA-encoding genes are shown in red boxes. In the common promoter, TATA boxes are marked by green triangles. Poly(A) signals are displayed with blue arrows. Numbers designate the distance between the regulatory transcription elements (in bp) and the length of each miRNA gene and intergenic spacer. The sequence of a mature miRNA duplex is presented in red color. Ago2: Argonaute-2; DGCR8: DiGeorge syndrome critical region gene 8; GW182: glycine-tryptophan protein of 182 kDa; MTDH: metadherin; PACT: protein kinase R-activating protein; Ran-GTP: GTP-binding nuclear protein Ran; SND1: staphylococcal nuclease domain-containing protein 1; TRBP: TAR RNA-binding protein.
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fig1: Biogenesis of human miR-221/222. miRNA-encoding genes are shown in red boxes. In the common promoter, TATA boxes are marked by green triangles. Poly(A) signals are displayed with blue arrows. Numbers designate the distance between the regulatory transcription elements (in bp) and the length of each miRNA gene and intergenic spacer. The sequence of a mature miRNA duplex is presented in red color. Ago2: Argonaute-2; DGCR8: DiGeorge syndrome critical region gene 8; GW182: glycine-tryptophan protein of 182 kDa; MTDH: metadherin; PACT: protein kinase R-activating protein; Ran-GTP: GTP-binding nuclear protein Ran; SND1: staphylococcal nuclease domain-containing protein 1; TRBP: TAR RNA-binding protein.

Mentions: In human DNA, the miR-221/222 gene cluster is located on chromosome Xp11.3 [38]. The miR-221 and miR-222 genes are separated by a distance of 726 bp (Figure 1). Nucleotide sequences of both genes share high similarity to each other. In fact, the genes are paralogues arisen from the duplication of the ancestral gene. They are transcribed as a single long noncoding RNA precursor with RNA polymerase II [39]. The promoter region contains two canonical TATA boxes located on 550 and 190 base pairs (bp) upstream of pre-miR-222. Three poly(A) signals are located downstream of pre-miR-221. The expression of the miR-221/222 gene cluster is positively regulated by angiotensin II [36] and downregulated by a repressive complex formed by estrogen receptor α and two nuclear receptor corepressors NCOR1 and NCOR2 [38].


Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling.

Chistiakov DA, Sobenin IA, Orekhov AN, Bobryshev YV - Biomed Res Int (2015)

Biogenesis of human miR-221/222. miRNA-encoding genes are shown in red boxes. In the common promoter, TATA boxes are marked by green triangles. Poly(A) signals are displayed with blue arrows. Numbers designate the distance between the regulatory transcription elements (in bp) and the length of each miRNA gene and intergenic spacer. The sequence of a mature miRNA duplex is presented in red color. Ago2: Argonaute-2; DGCR8: DiGeorge syndrome critical region gene 8; GW182: glycine-tryptophan protein of 182 kDa; MTDH: metadherin; PACT: protein kinase R-activating protein; Ran-GTP: GTP-binding nuclear protein Ran; SND1: staphylococcal nuclease domain-containing protein 1; TRBP: TAR RNA-binding protein.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4499635&req=5

fig1: Biogenesis of human miR-221/222. miRNA-encoding genes are shown in red boxes. In the common promoter, TATA boxes are marked by green triangles. Poly(A) signals are displayed with blue arrows. Numbers designate the distance between the regulatory transcription elements (in bp) and the length of each miRNA gene and intergenic spacer. The sequence of a mature miRNA duplex is presented in red color. Ago2: Argonaute-2; DGCR8: DiGeorge syndrome critical region gene 8; GW182: glycine-tryptophan protein of 182 kDa; MTDH: metadherin; PACT: protein kinase R-activating protein; Ran-GTP: GTP-binding nuclear protein Ran; SND1: staphylococcal nuclease domain-containing protein 1; TRBP: TAR RNA-binding protein.
Mentions: In human DNA, the miR-221/222 gene cluster is located on chromosome Xp11.3 [38]. The miR-221 and miR-222 genes are separated by a distance of 726 bp (Figure 1). Nucleotide sequences of both genes share high similarity to each other. In fact, the genes are paralogues arisen from the duplication of the ancestral gene. They are transcribed as a single long noncoding RNA precursor with RNA polymerase II [39]. The promoter region contains two canonical TATA boxes located on 550 and 190 base pairs (bp) upstream of pre-miR-222. Three poly(A) signals are located downstream of pre-miR-221. The expression of the miR-221/222 gene cluster is positively regulated by angiotensin II [36] and downregulated by a repressive complex formed by estrogen receptor α and two nuclear receptor corepressors NCOR1 and NCOR2 [38].

Bottom Line: 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).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 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus