Abstract. Liver dysfunction reflects the status of heart failure, and previous studies have demonstrated that serum lactate dehydrogenase (S-LDH) levels are increased in patients exhibiting heart failure and liver dysfunction. Right heart failure is a main characteristic of idiopathic pulmonary arterial hypertension (IPAH). The aim of the present study was to assess the prognostic significance of S-LDH levels in patients with IPAH. S-LDH levels were determined in 173 patients with IPAH, and these patients were subclassified into two groups according to a defined upper reference limit of S-LDH (250 IU/l). Right heart catheterization was performed in all patients. A total of 53 patients were found to have elevated S-LDH to ≥250 IU/l. In a mean follow-up period of 31.2±17.9 months, 57 patients succumbed. In the group with lower S-LDH levels (S-LDH <250 IU/l), 16.7% of the patients succumbed, compared with 69.8% of patients in the group with higher S-LDH levels (S-LDH ≥250 IU/l). The Kaplan-Meier survival curves demonstrated that patients with higher S-LDH levels had a significantly lower survival rate than did those with lower S-LDH levels (log-rank test, P<0.001). Cox proportional hazard analyses identified reduced body mass index, reduced cardiac index, elevated World Health Organization functional class, higher S-LDH and an absence of PAH-targeted therapy as significant predictors of adverse outcomes. In conclusion, elevated S-LDH is a risk factor for mortality in patients with IPAH.
Whether pulmonary arterial hypertension (PAH) is reversible in congenital heart disease (CHD) is important for the operability of CHD. However, little is known about that. Our research was aimed at exploring novel biomarkers and targets in the reversibility of CHD-PAH. CHD-PAH patients diagnosed with right heart catheterization (RHC) were enrolled (n = 14). Lung biopsy was performed during the repair surgery. After one year follow-up, mean pulmonary arterial pressures (mPAP) were evaluated by RHC to determine the diagnosis of reversible (mPAP < 25 mmHg, n = 10) and irreversible (mPAP ≥ 25 mmHg, n = 4) PAH. Harvested normal lung tissues (n = 6) were included as the control group. Pulmonary arteriole lesions were identified by pathological grading in tissue staining. iTRAQ-labelled mass-spectrometry analysis followed by immunohistochemistry and western blot was used to explore the most meaningful differential proteins. For enrolled patients, the histopathological grading of pulmonary vascular lesions in reversible CHD-PAH patients was all at grades 0–II while grades III–IV were shown only in irreversible CHD-PAH patients. Proteomic analysis identified 85 upregulated and 75 downregulated proteins, including cytoskeletal proteins and collagen chains, mainly involved in cell adhesion, extracellular matrix, cytoskeleton, immune response, and complement pathways. Among them, caveolin-1, filamin A expression, and cathepsin D combined with macrophagocytes counts were significantly increased; glutathione S-transferase mu1 (GSTM1) expression was significantly decreased in the irreversible CHD-PAH group (all P < 0.05). Caveolin-1, filamin A, and cathepsin D expression showed a positive relation and GSTM1 showed a negative relation with pathological grading. Upregulated caveolin-1, filamin A, and cathepsin D combined with increased macrophagocytes and downregulated GSTM1 may be potential biomarkers and targets in the irreversibility CHD-PAH, and which may be useful in evaluating the operability and understanding the irreversibility of CHD-PAH. Expression of these pathological biomarkers combined with pathological changes in lung biopsy may have great value in predicting the irreversibility of PAH.
These results suggest that PD173074 can alleviate monocrotaline-induced pulmonary arterial hypertension and it may be a useful option for PAH. Our data also suggest a role of FGF-2/bone morphogenetic protein signaling interaction in PAH.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.