tailieunhanh - Báo cáo y học: " Physiologic and molecular consequences of endothelial Bmpr2 mutation"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:" Physiologic and molecular consequences of endothelial Bmpr2 mutation. | Majka et al. Respiratory Research 2011 12 84 http content 12 1 84 RESPIRATORY RESEARCH RESEARCH Open Access Physiologic and molecular consequences of endothelial Bmpr2 mutation Cl I m vx K I 11 - 1 2 h ỉ v I V I_I S z t r DI-sr-l rAi m4 II I I 1 I_I I A I r r r v 4 Dz n e f I vr 3 susan ividjKd Moira Hagen ihomas DiacKweii Juiie Harrai Jennifer A Johnson Robert uendron I_I ex I ex ex D- r- I r 3 i l vr s 1 I KỲ o r E I z rr ỉ4 Ct r l I z ỉ I rd r -xx rr I 1 1 1 I e f D c Fz m-X r I 1 -X I I -X KỲ r r A z xr F4 neiene raraois Daniel crona James E Loyo Eva NoziK-uraycK Kuri R sienmarK ano James vvesi Abstract Background Puimonary arteriai hypertension PAH is thought to be driven by dysfunction of puimonary vascuiar microendotheiiai ceiis PMVEC . Most hereditary PAH is associated with BMPR2 mutations. However the physioiogic and moiecuiar consequences of expression of BMPR2 mutations in PMVEC are unKnown. Methods In vivo experiments were performed on aduit mice with conditionai endotheiiai-specific expression of the truncation mutation Bmpr2deix4 with age-matched transactivator-oniy mice as controis. Phenotype was assessed by RVSP counts of muscuiarized vesseis and proiiferating ceiis and staining for thromboses inflammatory ceiis and apoptotic ceiis. The effects of BMPR2 KnocKdown in PMVEC by siRNA on rates of apoptosis were assessed. Affymetrix expression arrays were performed on PMVEC isoiated and cuitured from tripie transgenic mice carrying the immortomouse gene a transactivator and either controi Bmpr2deix4 or Bmpr2R899X mutation. Results Transgenic mice showed increased RVSP and corresponding muscuiarization of smaii vesseis with histoiogic aiterations inciuding thrombosis increased inflammatory ceiis increased proiiferating ceiis and a moderate increase in apoptotic ceiis. Expression arrays showed aiterations in specific pathways consistent with the histoiogic changes. Bmpr2deix4 and Bmpr2R899X mutations resuited in very simiiar .