Wnt5a Increases Cardiac Gene Expressions of Cultured Human Circulating Progenitor Cells via a PKC Delta Activation

Background: Wnt signaling controls the balance between stem cell proliferation and differentiation and body patterning throughout development. Previous data demonstrated that non-canonical Wnts (Wnt5a, Wnt11) increased cardiac gene expression of circulating endothelial progenitor cells (EPC) and bone marrow-derived stem cells cultured in vitro. Since previous studies suggested a contribution of the protein kinase C (PKC) family to the Wnt5a-induced signalling, we investigated which PKC isoforms are activated by non-canonical Wnt5a in human EPC. Methodology/Principal Findings: Immunoblot experiments demonstrated that Wnt5a selectively activated the novel PKC isoform, PKC delta, as evidenced by phosphorylation and translocation. In contrast, the classical Ca2+-dependent PKC isoforms, PKC alpha and beta2, and one of the other novel PKC isoforms, PKC epsilon, were not activated by Wnt5a. The PKC delta inhibitor rottlerin significantly blocked co-culture-induced cardiac differentiation in vitro, whereas inhibitors directed against the classical Ca2+-dependent PKC isoforms or a PKC epsilon-inhibitory peptide did not block cardiac differentiation. In accordance, EPC derived from PKC delta heterozygous mice exhibited a significant reduction of Wnt5a-induced cardiac gene expression compared to wild type mice derived EPC. Conclusions/Significance: These data indicate that Wnt5a enhances cardiac gene expressions of EPC via an activation of PKC delta

Correlation between CT Value on Lung Subtraction CT and Radioactive Count on Perfusion Lung Single Photon Emission CT in Chronic Thromboembolic Pulmonary Hypertension

Background: Lung subtraction CT (LSCT), the subtraction of noncontrast CT from CT pulmonary angiography (CTPA) without spatial misregistration, is easily applicable by utilizing a software-based deformable image registration technique without additional hardware and permits the evaluation of lung perfusion as iodine accumulation, similar to that observed in perfusion lung single photon emission CT (PL-SPECT). The aim of this study was to use LSCT to newly assess the quantitative correlation between the CT value on LSCT and radioactive count on PL-SPECT as a reference and validate the quantification of lung perfusion by measuring the CT value in chronic thromboembolic pulmonary hypertension (CTEPH). Methods: We prospectively enrolled 47 consecutive patients with CTEPH undergoing both LSCT and PL-SPECT; we used noncontrast CT, CTPA, and LSCT to measure CT values and PL-SPECT to measure radioactive counts in areas representing three different perfusion classes—no perfusion defect, subsegmental perfusion defect, and segmental perfusion defect; we compared CT values on noncontrast CT, CTPA, and LSCT and radioactive counts on PL-SPECT among the three classes, then assessed the correlation between them. Results: Both the CT values and radioactive counts differed significantly among the three classes (p < 0.01 for all) and showed weak correlation (ρ = 0.38) by noncontrast CT, moderate correlation (ρ = 0.61) by CTPA, and strong correlation (ρ = 0.76) by LSCT. Conclusions: The CT value measurement on LSCT is a novel quantitative approach to assess lung perfusion in CTEPH and only correlates strongly with radioactive count measurement on PL-SPECT