LUNG METABOLISM--ENZYMES IN THE PULMONARY CIRCULATION

Tufts Medical Center, Boston MA

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Abstract

DESCRIPTION (Adapted from applicant's abstract and specific aims): Angiotensin 1 converting enzyme causes both vasoconstriction and vascular wall remodeling through the formation of angiotensin 2 and possibly by an activation of bradykinin. Alterations in ACE may participate in hypoxia-induced pulmonary hypertension. Thus, regulation of the synthesis of ACE is an important physiologic event in need of further study. The specific aims of this proposal are: 1) To better define mechanisms by which elevations of ACE occur by analysis of ACE gene transcription using nuclear run-off and mRNA stability by half-life studies; 2) To determine the role of promoter regions of the gene in the stimulation of ACE mRNA synthesis, with particular reference to oxygen-sensing response elements, by functional promoter analysis in transfected cells; and 3) To delineate specific promoter elements by DNase footprinting and assess the factors that bind these elements by electrophoretic mobility shift assay.