Changes of gene expression after bone marrow cell transfusion in rats with monocrotaline-induced pulmonary hypertension.
Pulmonary artery hypertension (PAH) causes right ventricular failure and possibly even death by a progressive increase in pulmonary vascular resistance. Bone marrow-derived mesenchymal stem cell therapy has provided an alternative treatment for ailments of various organs by promoting cell regeneration at the site of pathology. The purpose of this study was to investigate changes of pulmonary haemodynamics, pathology and expressions of various genes, including ET (endothelin)-1, ET receptor A (ERA), endothelial nitric oxide synthase (NOS) 3, matrix metalloproteinase (MMP) 2, tissue inhibitor of matrix metalloproteinase (TIMP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α in monocrotaline (MCT)-induced PAH rat models after bone marrow cell (BMC) transfusion. The rats were grouped as the control (C) group, monocrotaline (M) group, and BMC transfusion (B) group. M and B groups received subcutaneous (sc) injection of MCT (60 mg/kg). BMCs were transfused by intravenous injection at the tail 1 week after MCT injection in B group. Results showed that the average RV pressure significantly decreased in the B group compared with the M group. RV weight and the ratio of RH/LH+septum significantly decreased in the B group compared to the M group. Gene expressions of ET-1, ERA, NOS 3, MMP 2, TIMP, IL-6, and TNF-α significantly decreased in week 4 in the B group compared with the M group. In conclusion, BMC transfusion appears to improve survival rate, RVH, and mean RV pressure, and decreases gene expressions of ET-1, ERA, NOS 3, MMP 2, TIMP, IL-6, and TNF-α.
Department of Thoracic and Cardiovascular Surgery, Ewha Womans University, Seoul, Korea.
Kwan Chang
KC
Kim
Hae Ryun
HR
Lee
Sung Jin
SJ
Kim
Min-Sun
MS
Cho
Young Mi
YM
Hong
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D016276:Ventricular Function / Q000502:physiology
D016207:Cytokines; D004798:Enzymes; D016686:Monocrotaline