抄録
The role of Angiotensin II (Ang II) in the regulation of the cardiovascular system under normal and pathologic conditions have been well documented. A variety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are selected as first choice medicine for hypertension or heart failure. Although two major subtypes Ang II receptors, exist type1 (AT1) and type2 (AT2), most studies and treatments have focused on AT1 coupled events. Previous reports indicated that AT2 plays a role in essentially growth suppression such as through the tyrosine phoaphatase SHP-1 and MKP-1 activation. However, a detailed signaling mechanisms of these responses still remain unclear. Interestingly, an increasing number of recent reports indicate that AT2 plays a role in growth promoting similar to the AT1 function. We reported that AT2 gene-deleted mice lose the ability to develop cardiac hypertrophy in response to pressure overload or to chronic Ang II stimulation, and also found a novel signaling mechanism of AT2 mediated by the transcription factor promyelocytic leukemia zinc finger (PLZF) leading to cardiac hypertrophy. PLZF is selectively expressed in the heart, but not in the kidney or aorta. Upon Ang II stimulation, AT2 and PLZF are internalized, and PLZF translocates into the nucleus, whereby nuclear PLZF activates phosphoinositide 3-kinase (PI3K) regulatory subunit 85α leading to cardiac hypertrophy. However, in the absence of PLZF, Ang II evoked SHP-1 activation leading to growth suppression via AT2. These results suggest that AT2 may have dual switching functions mediated by PLZF. [J Physiol Sci. 2006;56 Suppl:S42]
