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Updated: Apr 28, 2026
Isolation of Murine Coronary Vascular Smooth Muscle Cells
Published on: May 30, 2016
miR-21 normalizes vascular smooth muscle proliferation and improves coronary collateral growth in metabolic syndrome
Rebecca Hutcheson1, Jennifer Chaplin2, Brenda Hutcheson1
1Department of Pharmacology, New York Medical College, Valhalla, New York, USA;
Abstract:
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.
Insights
Excessive cell proliferation, driven by miR-21 in metabolic syndrome, impairs coronary collateral growth (CCG). Blocking miR-21 improved CCG in rats, suggesting a therapeutic target for cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Regenerative Medicine
Background:
- Inadequate coronary collateral growth (CCG) is linked to impaired cell proliferation.
- Proangiogenic growth factors fail to improve CCG despite stimulating cell proliferation.
- Metabolic syndrome is associated with increased growth factors and impaired CCG.
Purpose of the Study:
- To investigate if excessive cell proliferation contributes to impaired CCG in metabolic syndrome.
- To explore the role of miR-21 in regulating cell proliferation and CCG in metabolic syndrome models.
Main Methods:
- Comparison of CCG and cell proliferation markers (PCNA, Ki-67, cyclin A, etc.) in normal (SD) and metabolic syndrome (JCR) rats subjected to repetitive ischemia (RI).
- Assessment of miR-21 expression levels in both rat models during RI.
- Intervention with anti-miR-21 therapy in JCR rats to evaluate its effect on cell proliferation and CCG.
Main Results:
- CCG was impaired in JCR rats compared to SD rats following RI.
- JCR rats exhibited greater and sustained cell proliferation than SD rats during RI.
- Sustained miR-21 expression in JCR rats correlated with excessive proliferation of vascular smooth muscle cells and impaired CCG.
- Anti-miR-21 treatment significantly improved CCG in JCR rats by reducing cell proliferation.
Conclusions:
- Excessive, miR-21-dependent cell proliferation during later stages of collateral remodeling is a key factor in impaired CCG in metabolic syndrome.
- Targeting miR-21 may offer a novel therapeutic strategy to enhance CCG in patients with metabolic syndrome and cardiovascular disease.
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