Abstract 195: Endothelin Converting Enzyme-1 (ECE1) is Essential in Adult Normal Physiology

Endothelin converting enzyme-1 (ECE1) catalyzes the conversion of inactive big endothelin 1 (ET1) to active ET1. Homozygous Ece1 knock out (KO) mice die in utero or at birth, displaying multiple abnormalities including mandibular hypoplasia and cardiac outflow tract malformations, in spite of the presence of ample tissue ET1. In contrast, increased ECE1 activity and circulating and/or tissue ET1 are associated with many adult cardiovascular diseases, including idiopathic pulmonary fibrosis (IPF), a chronic and fatal lung disease. There is an apparent paradox between the need for ET1 in development and its harmful effects in adult disease. Therefore, our lab developed a conditional Ece1 KO mouse, in which the gene is ablated following tamoxifen (tam) treatment. We hypothesized that ECE1 serves to localize ET1 signals to specific cell populations and is essential in adult normal physiology. We studied the following groups: mice given vehicle rather than tam, mice lacking tam-inducible Cre recombinase, mice ...