| First Author | Su W | Year | 2013 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 305 |
| Issue | 1 | Pages | H104-13 |
| PubMed ID | 23604714 | Mgi Jnum | J:198958 |
| Mgi Id | MGI:5499947 | Doi | 10.1152/ajpheart.00597.2012 |
| Citation | Su W, et al. (2013) Smooth muscle-selective CPI-17 expression increases vascular smooth muscle contraction and blood pressure. Am J Physiol Heart Circ Physiol 305(1):H104-13 |
| abstractText | Recent data revealed that protein kinase C-potentiated myosin phosphatase inhibitor of 17 kDa (CPI-17), a myosin phosphatase inhibitory protein preferentially expressed in smooth muscle, is upregulated/activated in several diseases but whether this CPI-17 increase plays a causal role in pathologically enhanced vascular smooth muscle contractility and blood pressure remains unclear. To address this possibility, we generated a smooth muscle-specific CPI-17 transgenic mouse model (CPI-17-Tg) and demonstrated that the CPI-17 transgene was selectively expressed in smooth muscle-enriched tissues, including mesenteric arteries. The isometric contractions in the isolated second-order branch of mesenteric artery helical strips from CPI-17-Tg mice were significantly enhanced compared with controls in response to phenylephrine, U-46619, serotonin, ANG II, high potassium, and calcium. The perfusion pressure increases in isolated perfused mesenteric vascular beds in response to norepinephrine were also enhanced in CPI-17-Tg mice. The hypercontractility was associated with increased phosphorylation of CPI-17 and 20-kDa myosin light chain under basal and stimulated conditions. Surprisingly, the protein levels of rho kinase 2 and protein kinase Calpha/delta were significantly increased in CPI-17-Tg mouse mesenteric arteries. Radiotelemetry measurements demonstrated that blood pressure was significantly increased in CPI-17-Tg mice. However, no vascular remodeling was detected by morphometric analysis. Taken together, our results demonstrate that increased CPI-17 expression in smooth muscle promotes vascular smooth muscle contractility and increases blood pressure, implicating a pathological significant role of CPI-17 upregulation. |
