Conference: 2018 PHA International PH Conference & Scientific Sessions
Release Date: 07.28.2018
Presentation Type: Abstracts
File Download: 2018 Conference Abstract 1001
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Abstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.
Proper management of ductus-dependent congenital heart disease (CHD) is always a great concern to pediatricians. Our previous study suggested MEK1/2 may play a role in the regulation of ductus arteriosus (DA) patent or constricted. Here, we present the mechanism’s study of MEK1/2 pathway on DA patency and that whether MEK1/2 inhibitor PD0325901 has therapy potentiality for keeping DA patency.
MEK1/2 expression in patent and constricted human DA tissues was measured and MEK1/2 pathway inhibition with respect to DA patency was tested in a mouse model via postnatal or prenatal administration of MEK1/2 inhibitor, PD0325901. Mechanisms of MEK1/2 inhibition and DA patency were explored in human DA smooth muscle cells (DASMCs).
Data indicated that MEK1/2 was differentially expressed between constricted and patent DA tissues. Post- or prenatal administration of PD0325901 maintained DA patency during the postnatal period. MEK1/2 inhibition may promote DA patency by reducing cytosolic calcium in DASMCs, which is associated with DA functional closure, and reducing the proliferation and migration of DASMCs, which is associated with DA anatomic closure.
MEK1/2 pathway may simultaneously regulate both functional and anatomic closure of DA. MEK1/2 inhibitor PD0325901 may hold therapeutic promise to keep DA patency.
Figure 1: Expression of MEK1/2 and its phosphorylated MEK1/2(p-MEK1/2), in patent and constricted DAs
Figure 2: The effectiveness of PD0325901 in maintaining DA patency
Figure 3: The mechanism of PD0325901-mediated DA patency
Figure 4: Schematic diagram of MEK1/2 signaling pathways and modulators regulating DASMC contraction, proliferation and migration