| First Author | Hori D | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 3 | Pages | e0174108 |
| PubMed ID | 28323879 | Mgi Jnum | J:246828 |
| Mgi Id | MGI:5919374 | Doi | 10.1371/journal.pone.0174108 |
| Citation | Hori D, et al. (2017) miR-181b regulates vascular stiffness age dependently in part by regulating TGF-beta signaling. PLoS One 12(3):e0174108 |
| abstractText | BACKGROUND: Endothelial dysfunction and arterial stiffening play major roles in cardiovascular diseases. The critical role for the miR-181 family in vascular inflammation has been documented. Here we tested whether the miR-181 family can influence the pathogenesis of hypertension and vascular stiffening. METHODS AND RESULTS: qPCR data showed a significant decrease in miR-181b expression in the aorta of the older mice. Eight miR-181a1/b1-/- mice and wild types (C57BL6J:WT) were followed weekly for pulse wave velocity (PWV) and blood pressure measurements. After 20 weeks, the mice were tested for endothelial function and aortic modulus. There was a progressive increase in PWV and higher systolic blood pressure in miR-181a1/b1-/- mice compared with WTs. At 21 weeks, aortic modulus was significantly greater in the miR-181a1/b1-/- group, and serum TGF-beta was found to be elevated at this time. A luciferase reporter assay confirmed miR-181b targets TGF-betai (TGF-beta induced) in the aortic VSMCs. In contrast, wire myography revealed unaltered endothelial function along with higher nitric oxide production in the miR-181a1/b1-/- group. Cultured VECs and VSMCs from the mouse aorta showed more secreted TGF-beta in VSMCs of the miR-181a1/b1-/- group; whereas, no change was observed from VECs. Circulating levels of angiotensin II were similar in both groups. Treatment with losartan (0.6 g/L) prevented the increase in PWV, blood pressure, and vascular stiffness in miR-181a1/b1-/- mice. Immunohistochemistry and western blot for p-SMAD2/3 validated the inhibitory effect of losartan on TGF-beta signaling in miR-181a1/b1-/- mice. CONCLUSIONS: Decreased miR-181b with aging plays a critical role in ECM remodeling by removing the brake on the TGF-beta, pSMAD2/3 pathway. |
