Impaired Apoptosis of Pulmonary Endothelial Cells Is Associated With Intimal Proliferation and Irreversibility of Pulmonary Hypertension in Congenital Heart Disease
Key result
Irreversible pulmonary hypertension in CHD is linked to impaired endothelial apoptosis via 100% Bcl-2 expression.
- P<0.001
- n=24
Why the study?
It is unclear why pulmonary hypertension in children with congenital heart disease is reversible after repair in some cases but irreversible in others, potentially due to failure of endothelial cell apoptosis leading to intimal proliferation.
Is impaired endothelial cell apoptosis associated with the irreversibility of pulmonary hypertension in patients with congenital heart disease?
Population
18 patients with CHD and PHT (7 reversible, 11 irreversible) and 6 control patients
Comparison
Reversible PHT vs irreversible PHT vs control patients
Design
Observational study assessing cellular and histologic markers in lung biopsy samples
Authors
Discussion
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Implication
Irreversible pulmonary hypertension in congenital heart disease is strongly associated with impaired endothelial cell apoptosis, antiapoptotic signaling from perivascular inflammatory cells, and intimal proliferation.
Key Points
- To identify the cellular and histologic mechanisms underlying why pulmonary hypertension becomes irreversible in some patients with congenital heart disease.
- Analyzed lung biopsy specimens from 24 individuals, including 18 congenital heart disease patients (7 with reversible and 11 with irreversible pulmonary hypertension) and 6 controls.
- Assessed pro- and antiapoptotic protein expression in vascular and perivascular cells, along with immunohistochemical markers of vasoactivity and neoangiogenesis (endothelial nitric oxide synthase, VEGF, and CD34).
- The antiapoptotic protein Bcl-2 was expressed in pulmonary endothelial cells in 100% of irreversible pulmonary hypertension cases, compared to 0% of reversible cases and controls (p < 0.001).
- Intimal proliferation was detected in 10 of 11 (91%) irreversible cases versus 0 of 7 (0%) reversible cases (p < 0.001), accompanied by higher antiapoptotic protein expression in perivascular T-cells (p < 0.01).
- Irreversible cases demonstrated compensatory upregulation of VEGF and neoangiogenesis at sites of vessel narrowing or occlusion compared to reversible cases (p < 0.001).
Study Design
Type
Observational (n=24)
Structured PICO
Is impaired endothelial cell apoptosis associated with the irreversibility of pulmonary hypertension in patients with congenital heart disease?
P
Population
24 patients, including 18 with congenital heart disease and pulmonary hypertension (7 reversible, 11 irreversible) and 6 controls, who provided lung biopsy samples.
C
Comparator
Reversible PHT vs. Irreversible PHT vs. Control patients
O
Outcome
Expression of antiapoptotic and proapoptotic markers (including Bcl-2), intimal proliferation, and markers of vasoactivity and neoangiogenesis (eNOS, VEGF, CD34) in lung biopsy samplessurrogate
Main Result
Absolute Event Rate: 100% vs 0%
p-value: p=<0.001
Irreversible pulmonary hypertension in congenital heart disease is strongly associated with impaired endothelial cell apoptosis, antiapoptotic signaling from perivascular inflammatory cells, and intimal proliferation.
Cite This Study
Lévy et al. (2007) conducted an observational in Pulmonary hypertension in congenital heart disease (n=24). Irreversible pulmonary hypertension vs. Reversible pulmonary hypertension and controls was evaluated on Expression of antiapoptotic protein Bcl-2 by pulmonary endothelial cells (p=<0.001). Irreversible pulmonary hypertension in congenital heart disease is strongly associated with impaired endothelial cell apoptosis (Bcl-2 expression in 100% vs 0% of reversible cases; p<0.001).