Table 1.
Targets of the miR-26 family. Known cell type-specific targets of the miR-26 family associated with cardiovascular disease.
| MiR-26 family member | Cell type | Targets | Functions | References |
|---|---|---|---|---|
| miR-26a | EC | SMAD1 | Targets a BMP/SMAD1-Id1-p21WAF/CIP1/p27 signaling axis to promote an anti-angiogenic program in ECs. Regulates pathological and physiological angiogenesis in vivo. MiR-26a neutralization increases angiogenesis, decreases infarct size, and improves heart function post-MI. |
Icli, B. et al., 2013 |
| miR-26a/b | CM | GSK3β KCNJ2 |
Inhibits Ang-II induced expression of ANF and β-MHC in CMs in vitro. Overexpression of miR-26a suppresses KCNJ2 and KIR2.1 expression and reduces AF in response to an atrial tachypacing model in-vivo. |
Zhang, Z.H. et al., 2013 Luo, X. et al., 2013 |
| miR-26b | CM | PLCβ1 | In response to transverse aortic constriction (TAC), overexpression of cardiac-specific miR-26b increases LV wall thickness, but no effect on LV ejection fraction. Neutralization of miR-26a and miR-26b had no effect on TAC-induced LV hypertrophy or function. |
Han, M. et al., 2012 |
| miR-26a | SMC | SMAD1/SMAD4 | Inhibits VSMC cell differentiation and apoptosis in vitro, implicating miR-26a in VSMC phenotypic phenotypic switching. Expression is reduced in aortic aneurysms in mice at time point associated with VSMC de-differentiation. |
Dey, B.K. et al., 2012 |
| miR-26a | FB | CTGF Collagen I | Expression of miR-26a is reduced in response to Ang-II. Overexpression of miR-26a inhibits NF-κB activity. Decreased miR-26a expression in patients with AS. May regulate calcification related genes such as BMP2, SMAD1 and ALPL. Neutralization of miR-26a in acute MI resulted in improved LV function and reduced myocardial fibrosis (Figure 3). |
Wei, C. et al., 2013 Nigam, V. et al., 2010 |
SMAD1= mothers against decapentaplegic homolog 1; ID1= inhibitor of DNA binding 1, p21WAF1/CIP1= cyclin dependent kinase inhibitor 1A; p27=cyclin dependent kinase inhibitor 1B; GSK3β=glycogen synthase kinase 3 beta; Kir2.1=potassium inwardly-rectifying channel subfamily J; GATA4=GATA binding protein 4; PLCβ1= phospholipase C beta; SMAD4= mothers against decapentaplegic homolog 4; Ang-II, angiotensin II; CTGF=connective tissue growth factor; BMP2=bone morphogenetic protein 2; ALPL=alkaline phosphatase liver/bone/kidney; EC, endothelial cells; CM, cardiomyocytes; SMC, vascular smooth muscle cells; FB, fibroblasts.