The genetic mechanisms that contribute to the development of cardiovascular disease have been largely unknown. In 20 June Nature, Michael Crackower and colleagues at Amgen Research Institute/Ontario Cancer Institute show that angiotensin-converting enzyme 2 is an essential regulator of heart function (Nature 2002, 417:822-828).

Crackower et al. used three rat models of hypertension and observed that angiotensin converting enzyme 2 (ace2) maps to a defined quantitative trait locus on the X chromosome in all hypertensive rat strains. In these animals, ACE2 messenger RNA and protein expression were markedly reduced.

In addition, they generated ACE2 knockout mice and observed impaired contractility, increased angiotensin II levels and upregulated hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescued the cardiac phenotype. But ACER (a Drosophila ACE2 homologue) mutant flies have defective heart morphogenesis.

"The paper by Crackower et al. embodies an...

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