In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 103, No. 12 ( 2008-12-05), p. 1393-1401
Abstract:
The epicardium plays an essential role in coronary artery formation and myocardial development, but signals controlling the development and differentiation of this tissue are not well understood. To investigate the role of platelet-derived growth factor receptor (PDGFR)β in development of epicardial-derived vascular smooth muscle cells (VSMCs), we examined PDGFR β −/− and PDGFR β epicardial mutant hearts. We found that PDGFR β −/− hearts failed to form dominant coronary vessels on the ventral heart surface, had a thinned myocardium, and completely lacked coronary VSMCs (cVSMCs). This constellation of defects was consistent with a primary defect in the epicardium. To verify that these defects were specific to epicardial derivatives, we generated mice with an epicardial deletion of PDGFRβ that resulted in reduced cVSMCs distal to the aorta. The regional absence of cVSMCs suggested that cVSMCs could arise from 2 sources, epicardial and nonepicardial, and that both were dependent on PDGFRβ. In the absence of PDGFRβ signaling, epicardial cells adopted an irregular actin cytoskeleton, leading to aberrant migration of epicardial cells into the myocardium in vivo. In addition, PDGF receptor stimulation promoted epicardial cell migration, and PDGFRβ-driven phosphoinositide 3′-kinase signaling was critical for this process. Our data demonstrate that PDGFRβ is required for the formation of 2 distinct cVSMC populations and that loss of PDGFRβ-PI3K signaling disrupts epicardial cell migration.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/CIRCRESAHA.108.176768
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2008
detail.hit.zdb_id:
1467838-X
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