ADAMs cut into heart failure

Cardiac hypertrophy is an adaptive response to an increase in blood pressure which, despite initial benefits, leads to heart failure and is an independent risk factor for cardiovascular disease. In January Nature Medicine, Masanori Asakura and colleagues from Osaka University Faculty of Medicine, Osaka, Japan show that shedding of heparin-binding epidermal growth factor (HB-EGF) by ADAM12 plays an important role in the development of cardiac hypertrophy.

Asakura et al. found that in cultured rat neonatal cardiomyocytes protein synthesis is increased after shedding of HB-EGF from the cell surface. These changes were completely abolished by a neutralizing antibody specific for HB-EGF or a metalloproteinase inhibitor KB-R7785. In addition, they identified ADAM12 as the protease causing the shedding of HB-EGF and the target protease for KB-R7785 (Nat Med 2001, 8:35-40).

"These results show that inhibition of HB-EGF shedding could be a potent therapeutic strategy for cardiac hypertrophy,"...