Reducing In-Stent Restenosis

McDonald, Robert; Halliday, Crawford A.; Miller, Ashley M.; Diver, Louise A; Dakin, Rachel; Montgomery, Jennifer; McBride, Martin W.; Kennedy, Simon; McClure, John; Robertson, Keith; Douglas, Gillian; Channon, Keith M.; Oldroyd, Keith G.; Baker, Andrew H.

doi:10.1016/j.jacc.2015.03.549

Cited by 93 publications

(55 citation statements)

References 35 publications

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“…Overexpression of miR-21 in mouse hearts inhibited ischemia-induced upregulation of PTEN and FasL, reduced infarct size and attenuated apoptosis [36]. Long-term elevation in miR-21, however, may lead to the development of cardiac fibrosis following ischemia/reperfusion injury [37], and is also deleterious by increasing vascular remodeling and restenosis after stent placement [38]. Our results showed that increased circulating miR-21 levels 5 days after PCI correlated with the cTnI (ρ = 0.399, p ≤ 0.0001) concentration and were higher in the LVR than the non-LVR group.…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction

et al. 2015

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Objectives: MicroRNA (miR)-146a and miR-21 have been reported to participate in inflammatory reactions and fibrosis. Excessive inflammation and cardiac fibrosis may play important roles in the development of left ventricular remodeling (LVR). This study assessed whether miR-146a, miR-21 and other biomarkers could predict LVR after myocardial infarction (MI). Methods: Circulating miR-146a, miR-21 and other biomarker levels were measured in 198 patients with acute MI 5 days after primary percutaneous coronary intervention (PCI). All patients were assessed by transthoracic echocardiography on day 5 and 1 year after primary PCI. Results: Concentrations of circulating miR-146a, miR-21, C-reactive protein, creatine kinase MB type and troponin I, as well as estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF), were significantly higher in patients with than in those without LVR (p < 0.05). Multivariate logistic regression analysis showed that circulating miR-146a (odds ratio, OR = 2.127, p < 0.0001), miR-21 (OR = 1.119, p < 0.0001), eGFR (OR = 0.939, p = 0.0137) and LVEF (OR = 0.802, p = 0.0048) were independent predictors of LVR development. The area under the curve for the combination of miR-146a and miR-21 was significantly higher than for either alone. Conclusion: Circulating miR-146a and miR-21 may be novel biomarkers predictive of LVR after acute MI. Their combination may better predict LVR than either alone.

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Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction

et al. 2015

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“…For example, it would be plausible to presume that targeting miR-21 in EC alters angiogenesis or antiinflammatory responses. 26,27,28,29 In agreement with earlier publications, we observed TAC-induced upregulation of miR-21 in both CF and EC, but not in cardiac myocytes (CM SHAM 1 ± 0.1 versus CM TAC 0.91 ± 0.2; CF SHAM 1 ± 0.07 versus CF TAC 3.87 ± 0.83,** P < 0.01; EC SHAM 1 ± 0.25 versus EC TAC 3.25 ± 0.84,* P < 0.05). 2,30 Furthermore, flow cytometry analysis indicated that the number of fibroblasts increased significantly while there was a significant decline in endothelial cell numbers (% of non-CM: CF SHAM 26.7 ± 0.43 versus CF TAC 33.…”

Section: Discussionmentioning

confidence: 99%

Viral Vector-Based Targeting of miR-21 in Cardiac Nonmyocyte Cells Reduces Pathologic Remodeling of the Heart

et al. 2016

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Systemic inhibition of miR-21 has proven effective against myocardial fibrosis and dysfunction, while studies in cardiac myocytes suggested a protective role in this cell type. Considering potential implications for therapy, we aimed to determine the cell fraction where miR-21 exerts its pathological activity. We developed a viral vector-based strategy for gene targeting of nonmyocyte cardiac cells in vivo and compared global to cardiac myocyte-specific and nonmyocyte-specific deletion of miR-21 in chronic left ventricular pressure overload. Murine moloney virus and serotype 9 of adeno-associated virus were engineered to encode improved Cre recombinase for genetic deletion in miR-21fl/fl mice. Pericardial injection of murine moloney virus-improved Cre recombinase to neonates achieved highly selective genetic ablation of miR-21 in nonmyocyte cardiac cells, identified as cardiac fibroblasts and endothelial cells. Upon left ventricular pressure overload, cardiac function was only preserved in mice with miR-21 deficiency in nonmyocyte cardiac cells, but not in mice with global or cardiac myocyte-specific ablation. Our data demonstrate that miR-21 exerts its pathologic activity directly in cardiac nonmyocytes and encourage further development of antimiR-21 therapy toward cellular tropism.

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“…Using a mouse vascular stent model, they demonstrate that the knockout of miR-21 can attenuate neointimal formation post-stenting modulating inflammation and VSMC response [238]. …”

Section: Angioplasty Stents and Mirsmentioning

confidence: 99%

microRNAs Distinctively Regulate Vascular Smooth Muscle and Endothelial Cells: Functional Implications in Angiogenesis, Atherosclerosis, and In-Stent Restenosis

Santulli

2015

microRNA: Basic Science

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Endothelial cells (EC) and vascular smooth muscle cells (VSMC) are the main cell types within the vasculature. We describe here how microRNAs (miRs)—noncoding RNAs that can regulate gene expression via translational repression and/or post-transcriptional degradation—distinctively modulate EC and VSMC function in physiology and disease. In particular, the specific roles of miR-126 and miR-143/145, master regulators of EC and VSMC function, respectively, are deeply explored. We also describe the mechanistic role of miRs in the regulation of the pathophysiology of key cardiovascular processes including angiogenesis, atherosclerosis, and in-stent restenosis post-angioplasty. Drawbacks of currently available therapeutic options are discussed, pointing at the challenges and potential clinical opportunities provided by miR-based treatments.

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Reducing In-Stent Restenosis

Cited by 93 publications

References 35 publications

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction

Viral Vector-Based Targeting of miR-21 in Cardiac Nonmyocyte Cells Reduces Pathologic Remodeling of the Heart

microRNAs Distinctively Regulate Vascular Smooth Muscle and Endothelial Cells: Functional Implications in Angiogenesis, Atherosclerosis, and In-Stent Restenosis

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