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Aims: Excessive vascular cell proliferation is an important component of pulmonary hypertension (PH). Perlecan is the major heparan sulfate (HS) proteoglycan in the vascular extracellular matrix. It binds growth factors, including FGF2, and either restricts or promotes cell proliferation. In this study, we have explored the effects of perlecan HS deficiency on pulmonary vascular development and in hypoxia-induced PH. Methods and results: In normoxia, Hspg23/3 mice, deficient in perlecan HS, had reduced pericytes and muscularization of intra-acinar vessels. Pulmonary angiography revealed a peripheral perfusion defect. Despite these abnormalities, right ventricular systolic pressure (RVSP) and myocardial mass remained normal. After 4 weeks of hypoxia, increases in the proportion of muscularized vessels, RVSP, and right ventricular hypertrophy were significantly less in Hspg23/3 compared with wild type. The early phase of hypoxia induced a significantly lower increase in fibroblast growth factor receptor-1 (FGFR1) protein level and receptor phosphorylation, and reduced pulmonary artery smooth muscle cell (PASMC) proliferation in Hspg23/3. At 4 weeks, FGF2 mRNA and protein were also significantly reduced in Hspg23/3 lungs. Ligand and carbohydrate engagement assay showed that perlecan HS is required for HS-FGF2-FGFR1 ternary complex formation. In vitro, proliferation assays showed that PASMC proliferation is reduced by selective FGFR1 inhibition. PASMC adhesion to fibronectin was higher in Hspg23/3 compared with wild type. Conclusions: Perlecan HS chains are important for normal vascular arborization and recruitment of pericytes to pulmonary vessels. Perlecan HS deficiency also attenuates hypoxia-induced PH, where the underlying mechanisms involve impaired FGF2/FGFR1 interaction, inhibition of PASMC growth, and altered cell-matrix interactions. [ABSTRACT FROM AUTHOR]

Abstract Purpose  Cor triatriatum sinister, more commonly referred to as cor triatriatum (CT), is characterized by a common pulmonary venous chamber (proximal chamber) separated from the left atrium (distal chamber) by a fibromuscular septum. This report of our experience updates the surgical results of this anomaly in the Asian population. Methods  Between January 1992 and May 2005, nine patients with cor triatriatum underwent surgical correction at Chang Gung Memorial Hospital. We retrospectively analyzed their cardiac anatomy, clinical data, surgical procedures and follow-up data. Results  The mean age at surgery was 260 215 days (range, 20–790 days), with the exception of one patient who underwent surgery at 31 years of age. Three patients had a partial anomalous pulmonary venous connection, one had a complete atrioventricular canal defect, and one had another major complex cardiac anomaly. Eight corrective operations and one palliative operation were performed. There was no surgical mortality. The mean follow-up time was 52.1 43.6 months (range, 17–139 months). Conclusion  Our findings show that surgical correction is efficient and safe for this rare cardiac anomaly. [ABSTRACT FROM AUTHOR]