Biology Reference
In-Depth Information
(Kim et al.
2005
; Muzaffar et al.
2008
). Data supporting the role of one or more
transcription factors in the regulation of PDEs in PAH would likely advance
understanding of PDEs and perhaps identify mechanisms that contribute to the
initiation and progression of PAH.
Real-time PCR and immunoblot analyses have demonstrated that a number of
other PDEs and PDE-related proteins, including the two isoforms of the small
inhibitory proteins PDE
g
1 and PDE
g
2, which were first shown to be associated
with PDE6 regulation in photoreceptor cells, are expressed in PASMCs; however,
they have not been shown to regulate the PDEs expressed in PASMCs and their
function and relevance to PAH have not been fully investigated (Fig.
1a
, Murray
et al.
2003
,
2007
). These or other PDEs may be highly expressed in the RV or in
inflammatory cells such as lymphocytes, macrophages, and DCs that infiltrate the
PA and may be as important to PAH as those outlined above. Further analyses of
the regulation, expression, and function of PDEs in the pulmonary circulation and
the effectiveness of combination therapy with PDE inhibitors would increase the
understanding of PAH and may aid in the development of novel therapeutic targets
or regimens.
Acknowledgment This work was supported by grants from the National Heart, Lung and Blood
Institute of the National Institutes of Health (K99HL091061), the Leukemia & Lymphoma Society
(7332-06), and the Ellison Medical Foundation (AG-SS-1662-06).
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