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Heritable pulmonary arterial hypertension (HPAH) is a rare type of pulmonary arterial hypertension that often presents with progressive exertional dyspnea and for which there is no significant effective drug. A HPAH patient was admitted to our hospital more than three years ago, and the gene mutation was bone morphogenetic protein 2 (BMPR2). For the first 45 months, she was given oral imatinib 100 mg once daily, and her symptoms and hemodynamics improved significantly, with no apparent side effects. It is reported that, in combination with the characteristics of the case and related literatures, it provides clinicians with other feasible treatment options for HPAH.

Objective To observe the effects of Bushen Tiaojing Recipe (BTR) on the counts of survival preantral follicles and the bone morphogenetic protein receptor II (BMPR II )/activin receptor- like kinase 6-drosophila mothers against decapentaplegic proteins (ALK6-Smads) signal pathway in oocytes cultured in vitro, and to study its mechanism for improving the quality of oocytes. Methods Prean- tral follicles were mechanically isolated from 65 female 12-day old healthy Kunming mice, which were inoculated by normal rats' serum (as the control group) , high, medium, low dose BTR containing serums (as Shen-supplementing groups) , high dose BTR containing serum + K02288 (as the inhibitor group) , respectively. All were cultured by common method in vitro. On the 6th day the counts of survival preantral follicles were compared between each Shen-supplementing group and the control group respectively. mR- NA expressions of BMPR II, ALK6, Smad1 , Smad5, and Smad8 were detected by Real-time fluorescence quantitative PCR. The protein expressions of indices mentioned above and phospho-Smadl/5/8 (p- Smadl/5/8) were detected by cellular immunofluorescence test. Results Compared with the control group, the quantity of survival preantral follicles increased in the high dose BTR containing serum group; mRNA expressions of BMPR II, ALK6, Smad5, and Smad8 were elevated, protein expressions of indi- ces mentioned above and p-Smadl/5/8 were increased in the 3 Shen-supplementing groups (P <0. 05) ; mRNA and protein expressions of Smad1 were increased in high and medium dose BTR containing serum groups (P<0.05). Compared with the high dose BTR containing serum group, protein expressions of Smad1/5/8 were reduced in the inhibitor group (P <0.05). Conclusion BTR could elevate the quantity of survival preantral follicles cultured in vitroand improve the quality of oocytes, which might be possibly as- sociated to regulating the BMPR II/ALK6-Smads signal pathway in oocytes.

Objective: To observe the effect of bone morphogenetic protein 4 (BMP4) on the Smad signaling pathway in rat distal pulmonary artery smooth muscle cells (PASMCs), and to explore the role of the transient receptor potential ion channel (TRPC) protein 1 and 6(TRPC1, 6) in rat distal PASMCs., Methods: Distal pulmonary arteries were isolated from adult male Wistar rats(n=6, 280-300 g). The endothelium-denuded pulmonary artery tissue was digested using Collagenase and PASMCs were cultured. Activation of BMP4 signaling pathway in Smad was detected by Western blotting. Western blotting was used for the measurement of protein to determine the involvement of BMP4/BMPRⅡ signaling in BMP4-inducd TRPC1 and TRPC6 protein expression, and Smad signaling was inhibited by the specific BMPRⅡ small interfering RNA (BMPRⅡSiRNA)., Results: Rapid phosphorylation of Smad1/5/8 was seen after 15 min of stimulation with BMP4, which was reduced with time. The BMPR Ⅱ proteins was effectively down-regulated in the PASMCs after transfection with BMPRⅡ SiRNA, and the phosphorylation of Smad1/5/8 BMP4-induced was decreased in the PASMCs transfected with BMPR Ⅱ SiRNA compared to the normal PASMCs. In addition, transfection of BMPRⅡsiRNA also attenuated BMP4-induced TRPC1 and TRPC6 protein expression compared with transfection of NT-target siRNA in distal PASMCs. PASMCs transfected with BMPRⅡsiRNA showed a markedly decreased ability for BMP4 induction as assessed by gray value ratio of Western blotting, 2.7 times and 2.5 times by TRPC1/β-actin and TRPC6/β-actin respectively, compared with NT siRNA-treated cells(P<0.05)., Conclusion: TRPC1 and TRPC6 protein expression can be up-regulated through Smad1/5/8 signaling activation by combination of BMP4 and BMPRⅡ in PASMCs.

Objective: To investigate the mechanism of myocardialization of proximal outflow tract septum and its effect on the conotruncal anomaly in mice., Methods: The C(57)/BL(6) mice of embryonic day (E) 11.5 - 16.5 were selected. The phenotypes of connexin 43 (Cx43) homozygotes (Cx43(-/-)), heterozygotes (Cx43(+/-)) and wild-types (Cx43(+/+)) were genetically typed by polymerase chain reaction (PCR). Bone morphogenetic protein receptor 2 (Bmpr2) and α-sarcomeric acti (α-SCA) were detected by immunohistochemistry., Results: The expression of α-SCA in the proximal outflow tract (OFT) septum was delayed obviously in Cx43(-/-) predominantly at E13.5 and E14.5. From E11.5 to E13.5, the expression of Bmpr2 was detected in cardiac atrium and epicardium of Cx43(+/+) fetal heart. And Bmpr2 was slightly expressed in ventricular muscle of Cx43(+/+) fetal heart. And it was expressed slightly only in cardiac atrium and epicardium of Cx43(+/-) and Cx43(-/-) fetal heart. From E14.5 to E16.5, its expression was detected obviously in cardiac atrium, epicardium, endocardium, trabeculum, ventricular muscle and OFT septum of Cx43(+/+) fetal heart. At E14.5, its expression was detected obviously in cardiac atrium, epicardium, endocardium and trabeculum of Cx43(+/-) and Cx43(-/-) fetal heart while none in ventricular muscle and OFT septum. At E15.5 and E16.5, its expression was detected obviously in cardiac atrium, epicardium, endocardium, trabeculum, ventricular muscle and OFT septum of Cx43(+/-) and Cx43(-/-) fetal heart. Its expression was also detected obviously in OFT septum of Cx43(+/-) and Cx43(-/-) fetal heart with incomplete myocardialization., Conclusion: Cx43KO embryonic mice exhibit delayed myocardialization. As compared with the Cx43(+/+), the expression of Bmpr2 in proximal OFT septum was delayed obviously in Cx43(+/-) and Cx43(-/-) mice. And the expression of Bmpr2 is abnormal in OFT septum of Cx43(+/-) and Cx43(-/-) fetal heart. Bmpr2 may be involved in the interaction between epicardium and myocardium. It may be a critical mechanism in the maturation process of cardiac muscles.