| First Author | Chan JC | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 3 | Pages | 785-90 |
| PubMed ID | 15637153 | Mgi Jnum | J:96458 |
| Mgi Id | MGI:3530681 | Doi | 10.1073/pnas.0407234102 |
| Citation | Chan JC, et al. (2005) Hypertension in mice lacking the proatrial natriuretic peptide convertase corin. Proc Natl Acad Sci U S A 102(3):785-90 |
| abstractText | Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates blood pressure. In cardiomyocytes, the hormone is synthesized as a precursor, proatrial natriuretic peptide (pro-ANP), which is proteolytically converted to active ANP. Corin is a cardiac transmembrane serine protease that has been shown to process pro-ANP in vitro, but its physiological importance had not been established. Here, we show that corin-deficient (Cor-/-) mice develop normally during embryogenesis and survive to postnatal life. Cor-/- mice have elevated levels of pro-ANP but no detectable levels of ANP as compared with WT littermates. Infusion of an active recombinant soluble corin transiently restores pro-ANP conversion, resulting in the release of circulating biologically active ANP. Using radiotelemetry to assess blood pressure, we find that Cor-/- mice have spontaneous hypertension as compared with WT mice, and it is enhanced after dietary salt loading. Pregnant Cor-/- mice demonstrate late-gestation proteinuria and enhanced high blood pressure during pregnancy. In addition, Cor-/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Thus, our data establish corin as the physiological pro-ANP convertase and indicate that corin deficiency may contribute to hypertensive heart disease. |
