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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Lung Biology and Pathology Study Section (LBPA)
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Tufts University
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