Larger Pipe, Lower Resistance

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Science  24 Mar 2006:
Vol. 311, Issue 5768, pp. 1677
DOI: 10.1126/science.311.5768.1677c

The pathogenesis of hypertension—a risk factor for heart disease, kidney disease, and stroke—is complex and poorly understood. Zacchigna et al. find that mice lacking elastin microfibril interface-located protein 1 (Emilin1), a secreted extracellular matrix protein expressed in the cardiovascular system, had high blood pressure in conjunction with decreased blood vessel diameter and increased peripheral resistance. Emilin1 contains a cysteine-rich domain, as do other proteins involved in the regulation of growth factor signaling, leading the authors to investigate the relationship between Emilin1 and transforming growth factor-β (TGF-β), which plays a critical role in vascular development and pathophysiology. Emilin1 blocked TGF-β signaling upstream of receptor activation and did not interfere with ligand/receptor binding or signaling in response to mature TGF-β1. Rather, Emilin1 bound to proTGF-β1, preventing its proteolytic processing and the production of biologically active TGF-β1. TGF-β signaling was enhanced in the aortic wall of the mice lacking Emilin1, and inactivation of one TGF-β1 allele in Emilin1 knockout mice restored normal blood vessel diameter and blood pressure. Thus, the authors conclude that Emilin1 acts to regulate blood pressure by modulating TGF-β processing and thus the availability of the biologically active form. — EMA

Cell 124, 929 (2006).

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