Abstract

Our model of the renin-angiotensin system has become increasingly complex with the identification of new components and additional roles for angiotensin peptides and their receptors. A functional (pro)renin receptor has been cloned. It acts as (pro)renin co-factor on the cell surface, enhancing the efficiency of angiotensinogen cleavage by (pro)renin and unmasking prorenin catalytic activity. Binding of (pro)renin to the receptor mediates (pro)renin cellular effects by activating MAP kinases ERK1/2. Immunofluorescence studies have located the receptor on mesangial and vascular smooth-muscle cells in human heart and kidney. This suggests that the renin receptor may represent a mean of capturing (pro)renin from the circulation and concentrating it at the interface between smooth-muscle and endothelial cells. This recent discovery of a functional (pro)renin receptor forces the emergence of a new concept that casts renin as potentially playing a direct role in tissue damage, especially in situations where the tissue RAS is activated.

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