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Onset and evolution of pulmonary vascular disease in young children: abnormal postnatal remodelling studied in lung
1Department of Paediatric Cardiology, Institute of Child Health, London, U.K.
Insights
Pulmonary vascular disease in children with congenital heart disease starts at birth, involving abnormal remodeling of pulmonary arteries. This early vascular remodeling leads to severe obliterative pulmonary vascular disease.
Area of Science:
- Cardiovascular Research
- Pediatric Pathology
- Pulmonary Hypertension
Background:
- Congenital heart disease (CHD) can lead to severe pulmonary hypertension (PH).
- Understanding the early structural changes in pulmonary arteries is crucial for managing pediatric PH associated with CHD.
Purpose of the Study:
- To investigate the structural and cellular changes in pulmonary arteries of children with severe PH and CHD.
- To determine the onset and progression of pulmonary vascular remodeling in this population.
Main Methods:
- Examination of lung biopsies from 26 children (2 months-18 years) with severe PH-CHD using light, transmission, and scanning electron microscopy.
- Qualitative and quantitative analyses were performed and compared to age-matched controls.
Main Results:
- Early signs of smooth muscle cell hyperplasia, hypertrophy, and accelerated differentiation were observed within 2 months.
- Intimal proliferation with smooth muscle cells occurred by 7 months, accompanied by excessive medial connective tissue.
- Endothelial cells were abnormally thickened and elongated, with cytoskeletal remodeling evident.
Conclusions:
- Pulmonary vascular disease in children with PH-CHD begins at or shortly after birth.
- Abnormal pulmonary vascular remodeling is a key feature, progressing to obliterative disease.
Abstract:
Pulmonary arterial structure was examined in lung biopsies from 26 children with severe pulmonary hypertensive congenital heart disease, aged 2 months-18 years, in whom the mean pulmonary arterial pressure was 55 (range 35-105) mmHg, using light, transmission, and scanning electron microscopy. Qualitative and quantitative techniques were applied and findings compared with those in age-matched controls. At 2 months, the smooth muscle cells showed hyperplasia, hypertrophy (mean cell diameter increased, P less than 0.001), and accelerated differentiation. In all pulmonary hypertensive cases aged less than 6 months, the contractile myofilament concentration was similar to the normal concentration at 6 months. Medial connective tissue was excessive for age. Smooth muscle cells within the intima (intimal proliferation) were first seen at 7 months, lying beneath a new internal elastic lamina. They showed a reduction in myofilament concentration in the more fibrotic lesions. In all cases, endothelial cells were abnormally thick (P less than 0.001) and elongated. Cytoskeletal remodelling was indicated by an increase in micro- and intermediate filament volume density (P less than 0.05 for both). The severity of endothelial damage was related to vessel size and position in the arterial pathway. These findings indicate that pulmonary vascular disease begins at or soon after birth with abnormal pulmonary vascular remodelling which leads to obliterative pulmonary vascular disease.