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Michael A. Crackower, Renu Sarao, Chana Yagil, Yoram Yagil, Josef M. Penninger, P-144: ACE2 - a novel candidate gene for hypertension, American Journal of Hypertension, Volume 14, Issue S1, April 2001, Page 78A, https://doi.org/10.1016/S0895-7061(01)01753-8
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Abstract
ACE2 is a recently identified homologue of ACE that has been shown to cleave Ang I to Ang 1-9, which can subsequently be cleaved to Ang 1-7, a potent vaso-depressor peptide. We hypothesize that loss of ACE2 expression leads to a decrease in Ang 1-7, causing an imbalance of pressor/depressor peptide levels and an increase in systemic arterial pressure. We have independently cloned rat ACE2. Radiation hybrid mapping placed ACE2 on the X chromosome within a defined QTL identified by positional cloning in the Sabra salt-sensitive model of hypertension. Overlapping QTLs have also been identified in SHRSP and SHR rats models of hypertension. ACE2 expression, measured by Northern analysis, was diminished in hypertensive SBH/y (35± 10% of control, N=4) compared to normotensive SBN/y. Western blotting with an ACE2 antibody revealed similar reduction in levels of ACE2 protein (48± 13% in SBH/y compared to SBN/y, N=4) and in SHR and SHRSP (51± 2.5% of control, N=4) compared to normotensive WKY. The experimental data obtained thus far lend support to a novel mechanism for hypertension according to which: (1) ACE2 is a regulator of vascular tone that counterbalances ACE activity, and that (2) in the presence of reduced ACE2 expression and vaso-depressor peptide levels, ACE activity predominates, leading to increased vascular tone and consequently hypertension. ACE2 is thus a novel candidate gene for hypertension.
