[HTML][HTML] Therapeutic Engagement of the Histone Deacetylase IIA–Myocyte Enhancer Factor 2 Axis Improves Experimental Pulmonary Hypertension
A Sofer, S Lee, I Papangeli, T Adachi… - American Journal of …, 2018 - atsjournals.org
American Journal of Respiratory and Critical Care Medicine, 2018•atsjournals.org
Methods To investigate the role of endothelial MEF2 function in the pathogenesis of PH, we
generated adult mice with inducible, endothelial-specific deletion of the Mef2c allele, using a
tamoxifen-responsive Cdh5 promoter–driven Cre recombinase crossed to mice with Mef2c
fl/fl alleles (henceforth called Mef2c ECKO mice)(6, 7). Invasive hemodynamic and
morphometric parameters were assessed at baseline and after exposure to 3 weeks of
chronic hypoxia (10% F i O 2). For the SU-5416/hypoxia rat models, male Sprague-Dawley …
generated adult mice with inducible, endothelial-specific deletion of the Mef2c allele, using a
tamoxifen-responsive Cdh5 promoter–driven Cre recombinase crossed to mice with Mef2c
fl/fl alleles (henceforth called Mef2c ECKO mice)(6, 7). Invasive hemodynamic and
morphometric parameters were assessed at baseline and after exposure to 3 weeks of
chronic hypoxia (10% F i O 2). For the SU-5416/hypoxia rat models, male Sprague-Dawley …
Methods
To investigate the role of endothelial MEF2 function in the pathogenesis of PH, we generated adult mice with inducible, endothelial-specific deletion of the Mef2c allele, using a tamoxifen-responsive Cdh5 promoter–driven Cre recombinase crossed to mice with Mef2c fl/fl alleles (henceforth called Mef2c ECKO mice)(6, 7). Invasive hemodynamic and morphometric parameters were assessed at baseline and after exposure to 3 weeks of chronic hypoxia (10% F i O 2). For the SU-5416/hypoxia rat models, male Sprague-Dawley rats (200–250 g) were injected subcutaneously with SU-5416 (Sigma; 20 mg/kg body weight). For drug administration, rats were given injections of either vehicle or TMP269 (50 mg/kg of body weight intraperitoneally; DC Chemical), or Tasquinimod (10 mg/kg body weight by oral gavage; DC Chemical) daily.
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