Journal
CELL
Volume 124, Issue 5, Pages 929-942Publisher
CELL PRESS
DOI: 10.1016/j.cell.2005.12.035
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Funding
- Telethon [GGP04030] Funding Source: Medline
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TGF-beta proteins are main regulators of blood vessel development and maintenance. Here, we report an unprecedented link between TGF-beta signaling and arterial hypertension based on the analysis of mice mutant for Emilin1, a cysteine-rich secreted glycoprotein expressed in the vascular tree. Emilin1 knockout animals display increased blood pressure, increased peripheral vascular resistance, and reduced vessel size. Mechanistically, we found that Emilin1 inhibits TGF-beta signaling by binding specifically to the proTGF-beta precursor and preventing its maturation by furin convertases; in the extracellular space. In support of these findings, genetic inactivation of Emifin1 causes increased TGF-beta signaling in the vascular wall. Strikingly, high blood pressure observed in Emilin1 mutants is rescued to normal levels upon inactivation of a single TGF-beta 1 allele. This study highlights the importance of modulation of TGF-beta availability in the pathogenesis of hypertension.
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