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Background Endothelial dysfunction is a characteristic pathophysiology of pulmonary arterial hypertension (PAH). Some paracrine factors secreted by bone marrow-derived endothelial progenitor cells (BMDEPC) have the potential to protect endothelial integrity and function. This study investigated whether BMDEPC enhances production of vasoprotective substances through paracrine action in pulmonary arteries of monocrotaline (MCT)-induced PAH. Methods and Results Mononuclear cells were obtained from femoral bone marrow of normal F344 rats and cultured for seven days to yield BMDEPC. Pulmonary arteries were exposed to BMDEPC (5×10 6 cells) in vitro or in vivo. Three weeks later, cyclooxygenase-2 (COX-2) expression, prostacyclin (PGI 2 ) and cAMP release were examined in isolated pulmonary arteries. Treatment with BMDEPC improved the pulmonary artery relaxation of MCT-induced PAH, and BMDEPC were observed in the pulmonary bed. Further analysis demonstrated increased protein expression of COX-2 in all three layers of arteries transplanted with BMDEPC. And, release of PGI 2 and content of cAMP were significantly enhanced. Moreover, the increased release of PGI 2 and cAMP were reversed only by a selective COX-2 inhibitor. Treatment with conditioned media obtained from BMDEPC exerted the same effect of BMDEPC on pulmonary artery in vitro or in vivo. Conclusions Transplantation of BMDEPC effectively ameliorates MCT-induced PAH. Growth factors secreted in a paracrine manner by BMDEPC promotes vasoprotection by increasing the release of PGI 2 and content of cAMP. Furthermore, the COX-2/PGI 2 synthase pathway appears to take a major responsibility for this effect.

Objective To study the effect of β-blocker, bisoprolol on the hypertrophy of cardiomyocytes of neonatal rats induced by high glucose levels, and investigate the mechanism of PKC signal transduction pathway on the structure, function alterations of cardiomyocytes cultured in high glucose levels. Methods Using cultured neonatal cardiac myocytes as a model, groups were divided into: control group (glucose level 5 mmol/l); high glucose group (glucose level 25.5 mmol/l); high glucose (glucose level 25.5 mmol/l)+bisoprolol (10 mmol/l); high glucose (glucose level 25.5 mmol/l)+bisoprolol (40 mmol/l); high glucose (glucose level 25.5 mmol/l)+NF-κB inhibitor (BAY11–7082, 5 mmol/l). The cardiomyocytes were cultured for 48 h in different groups after adding corresponding treat factors, the cellular contracting frequency was counted, the cardiomyocytes9 diameters were measured and the expression of PKCα, PKCβ 2 , p-PKCα, p-PKCβ 2 , NF-κB, TNFα and c-fos were measured by western blot and RT-PCR. Results Compared with control group, neonatal cardiomyocytes cultured in high glucose concentration showed an increased pulsatile frequency, cellular diameters and higher expression of PKCα, PKCβ 2 , p-PKCα, p-PKCβ 2 , NF-κB, TNFα and c-fos, β-blocker, bisoprolol, and NF-κB inhibitor BAY11–7082 could reverse these changes induced by high glucose concentration. Conclusions High glucose levels could induce hypertrophy of cardiomyocytes, β-blocker, bisoprolol can reverse the effect of high glucose on the cardiac myocytes; it may have a protective effect on diabetic cardiomyopathy via PKC/NF-κB/c-fos passageway.