miR-21 normalizes vascular smooth muscle proliferation and improves coronary collateral growth in metabolic syndrome

Autor: Jennifer Chaplin, James C. Russell, Brenda Hutcheson, Spencer D. Proctor, Petra Rocic, Rebecca Hutcheson, Sarah A. Gebb, Faye Borthwick, Erika Smith, Rashmi Jadhav
Rok vydání: 2014
Předmět:
Male
congenital
hereditary
and neonatal diseases and abnormalities
medicine.medical_specialty
Vascular smooth muscle
Cyclin A
Blotting
Western
Ischemia
Myocardial Ischemia
Collateral Circulation
Apoptosis
Coronary Artery Disease
Real-Time Polymerase Chain Reaction
Biochemistry
Muscle
Smooth
Vascular
Research Communications
Immunoenzyme Techniques
Rats
Sprague-Dawley
Coronary circulation
Internal medicine
Coronary Circulation
Genetics
Medicine
Animals
RNA
Messenger
Molecular Biology
Cells
Cultured
Cell Proliferation
Metabolic Syndrome
biology
Neovascularization
Pathologic
business.industry
Cell growth
Reverse Transcriptase Polymerase Chain Reaction
Cell cycle
Collateral circulation
medicine.disease
Rats
Disease Models
Animal
MicroRNAs
medicine.anatomical_structure
Endocrinology
biology.protein
Arteriogenesis
business
Biotechnology
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 28(9)
ISSN: 1530-6860
Popis: Inadequate cell proliferation is considered a major causative factor for impaired coronary collateral growth (CCG). Proangiogenic growth factors (GFs) stimulate cell proliferation, but their administration does not promote CCG in patients. These GFs are increased in patients with metabolic syndrome and in animal models, where CCG is impaired. Here, we investigated whether excessive cell proliferation underlies impaired CCG in metabolic syndrome. Normal [Sprague-Dawley (SD)] and metabolic syndrome [James C. Russell (JCR)] rats underwent repetitive ischemia (RI; transient, repetitive coronary artery occlusion and myocardial ischemia). We have shown that CCG was maximal at d 9 of RI in SD rats but did not occur in JCR rats. The increase in cell proliferation (PCNA, Ki-67, cyclin A, phospho- cdc2, p21Waf, p27Kip) was transient (∼4-fold, d 3 RI) in SD rats but greater and sustained in JCR rats (∼8- to 6-fold, d 3–9 RI). In JCR rats, this was associated with increased and sustained miR-21 expression and accumulation of proliferating synthetic vascular smooth muscle cells in the lumen of small arterioles, which failed to undergo outward expansion. Administration of anti-miR-21 blocked RI-induced cell proliferation and significantly improved CCG in JCR rats (∼60%). miR-21-dependent excessive cell proliferation in the later stages of collateral remodeling correlates with impaired CCG in metabolic syndrome.—Hutcheson, R., Chaplin, J., Hutcheson, B., Borthwick, F., Proctor, S., Gebb, S., Jadhav, R., Smith, E., Russell, J. C., Rocic, P. miR-21 normalizes vascular smooth muscle proliferation and improves coronary collateral growth in metabolic syndrome.
Databáze: OpenAIRE
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