| First Author | Wang Q | Year | 2018 |
| Journal | Oncotarget | Volume | 9 |
| Issue | 37 | Pages | 24601-24618 |
| PubMed ID | 29872491 | Mgi Jnum | J:316490 |
| Mgi Id | MGI:6835819 | Doi | 10.18632/oncotarget.23628 |
| Citation | Wang Q, et al. (2018) Olmesartan attenuates pressure-overload- or post-infarction-induced cardiac remodeling in mice. Oncotarget 9(37):24601-24618 |
| abstractText | Either angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor 1 blocker (ARB) attenuates cardiac remodeling. However, the overall molecular modulation of the reversing remodeling process in response to the ACEI or ARB treatment is not yet well determined. In this study, we examined whether gene expressions are modulated by ACEI (temocapril), ARB (olmesartan) or both in a murine model with transverse aortic constriction (TAC) and confirm whether periostin is a target gene of olmesartan in mice with myocardial infarction (MI). We detected 109 genes that were significantly up-regulated in TAC mice and a majority of these were down-regulated in response to temocapril, olmesartan or their combination which significantly attenuated cardiac remodeling at one or four weeks. Real-time RT-PCR demonstrated that olmesartan, temocapril or their combination down-regulated the expression of periostin. In MI mice treated with olmesartan for 4 weeks, the left ventricular end-diastolic and systolic dimensions measured with echocardiography were lower, whereas maximum rate of rise and fall rate of LV pressure (+/-dp/dt max) were greater, and Azan-staining cardiac fibrotic area was smaller. Furthermore, periostin was upregulated in response to MI, whereas olmesartan blocked this upregulation. Post-MI fibrosis was smaller in periostin knockout adult mice than in wildtype mice, while glycogen synthase kinase 3beta was increased and cyclin D1 was decreased in periostin knockout mice. These findings indicate that periostin is a target gene of ARB and olmesartan reverses cardiac remodeling at least partially through the downregulation of periostin. |
