PDGF-A IS REQUIRED FOR NORMAL MURINE CARDIOVASCULAR DEVELOPMENT

Several lines of evidence suggest that platelet-derived growth factor A chain (PDGF-A) is required for normal embryonic cardiovascular devel opment. To test this directly, we introduced anti-PDGF-A neutralizing antibodies into mouse deciduas in utero at Embryonic Days (E) 8.5, 9.5 , and 10.5. This resulted in the selective disruption of PDGF-A ligand -receptor interactions in vivo for a period of 18-24 hr and allowed us to assess both if PDGF-A is required for cardiovascular development a nd when it is required. Embryos collected 48 hr after antibody treatme nt displayed severe cardiovascular abnormalities. These included both atrial and ventricular myocardial hypertrophy, epicardial and endocard ial abnormalities, and aortic dilation, among others. Although heart a bnormalities were observed in embryos treated at all three ages, they were more common in embryos treated at E8.5. In contrast, only embryos treated at E10.5 exhibited significant aortic dilation. This work (1) demonstrates directly for the first time that PDGF-A is required for normal cardiovascular development, (2) identifies several processes th at require PDGF-A, and (3) defines discreet developmental periods duri ng which these PDGF-A-dependent processes require the factor. (C) 1996 Academic Press, Inc.