Impaired Apoptosis of Pulmonary Endothelial Cells Is Associated With Intimal Proliferation and Irreversibility of Pulmonary Hypertension in Congenital Heart Disease
Marilyne Lévy, MD, PhD*, ,*,
Christelle Maurey, DVM*,
David S. Celermajer, MBBS, DSc, FRACP ,
Pascal R. Vouhé, MD,
Claire Danel, MD*,
Damien Bonnet, MD, PhD and
Dominique Israël-Biet, MD*,||
* UPRES EA4068, UFR Biomédicale des Saints P res et Faculté de Médecine Paris V, Paris, France
Service de Chirurgie Cardiaque, Hôpital Necker-Enfants Malades, Paris, France
Faculty of Medicine, University of Sydney, Sydney, Australia
Service de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, Faculté de Médecine Paris V, Paris, France
|| Service de Pneumologie, Hôpital Européen Georges Pompidou, Paris, France
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Figure 1 Lung Biopsy Sections Showing Histological Changes in Intra-Acinar Pulmonary Arteries in Reversible PHT and Irreversible PHT
(A) Increased wall thickness (arrow) and thin and regular intimal layer (arrowhead). (B) Increased wall thickness (arrow) associated with intimal thickening (arrowhead) in irreversible pulmonary hypertension (PHT).
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Figure 2 Vascular Immunostaining for Markers of Apoptosis in Reversible PHT and Irreversible PHT
The antiapoptotic protein Bcl-2 is not expressed in reversible pulmonary hypertension (PHT), but by endothelial cells of severely damaged pulmonary arteries in irreversible PHT in all cases (A). Endothelial cells of both groups expressed markers of apoptosis caspase-3 (B) and p53 (C). The arrow indicates immunostaining in the endothelial layer.
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Figure 3 Apoptotic Properties of Inflammatory Cells in the Bronchovascular Area in Reversible PHT or Irreversible PHT
In irreversible pulmonary hypertension (PHT) the antiapoptotic protein Bcl-2 (A) is strongly expressed by inflammatory cells, whereas immunostaining for apoptotic markers is very low. The proapoptotic proteins caspase-3 (B) and p-53 (C) are strongly expressed by inflammatory cells in reversible PHT.
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Figure 4 Immunostaining for Markers of Angiogenesis in Patients With Reversible PHT and Irreversible PHT Compared With Control Patients
Endothelial immunostaining (arrows) for endothelial nitric oxide synthase (eNOS) (A) is more pronounced in irreversible pulmonary hypertension (PHT) than in reversible PHT and weakly expressed in control patients. Immunostaining for vascular endothelial growth factor (VEGF) (B) is weak in reversible PHT and control patients and strongly expressed in endothelial cells in irreversible PHT. Strong endothelial CD34 immunostaining (arrows) shows neovessels surrounding pulmonary arteries with severe intimal damage (C).
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