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Changes of gene expression after bone marrow cell transfusion in rats with monocrotaline-induced pulmonary hypertension.

Kim KC, Lee HR, Kim SJ, Cho MS, Hong YM - J. Korean Med. Sci. (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, Ewha Womans University, Seoul, Korea.

ABSTRACT
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.

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Related in: MedlinePlus

Morphometric analysis of pulmonary arteries. The external diameter (D), across the smallest diameter, and the medial wall thickness between the internal and external elastic lamina of two sides of muscular arteries (M1 and M2) were measured. The percentage of wall thickness was calculated as follows: % wall thickness = (M1 + M2)/D × 100 (H&E staining, × 400).
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Figure 1: Morphometric analysis of pulmonary arteries. The external diameter (D), across the smallest diameter, and the medial wall thickness between the internal and external elastic lamina of two sides of muscular arteries (M1 and M2) were measured. The percentage of wall thickness was calculated as follows: % wall thickness = (M1 + M2)/D × 100 (H&E staining, × 400).

Mentions: Lung tissue was fixed with 10% buffered formalin with gentle perfusion through the trachea for 24 hr and then embedded in paraffin. Three µm-thick sections were stained with Victoria blue to evaluate histopathologic changes of pulmonary blood vessels. More than 20 images of pulmonary arterioles (50-160 µm diameters) per tissue section at a magnification of 400 × were captured using a microscopic digital camera and analyzed using an image analysis program (analySIS, Olympus Soft Imaging Solutions, Singapore). The external diameter (D), across the smallest diameter, and the medial wall thickness between the internal and external elastic lamina of two sides of muscular arteries (M1 and M2) were measured. The percentage of wall thickness was calculated as follows: % wall thickness = (M1 + M2)/D × 100 (Fig. 1). In addition, the number of muscular arteries accompanied by respiratory bronchioli and present in alveolar wall were counted. A total of 20 randomly selected microscopic fields per tissue section at a magnification (200 ×) were assessed.


Changes of gene expression after bone marrow cell transfusion in rats with monocrotaline-induced pulmonary hypertension.

Kim KC, Lee HR, Kim SJ, Cho MS, Hong YM - J. Korean Med. Sci. (2012)

Morphometric analysis of pulmonary arteries. The external diameter (D), across the smallest diameter, and the medial wall thickness between the internal and external elastic lamina of two sides of muscular arteries (M1 and M2) were measured. The percentage of wall thickness was calculated as follows: % wall thickness = (M1 + M2)/D × 100 (H&E staining, × 400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369445&req=5

Figure 1: Morphometric analysis of pulmonary arteries. The external diameter (D), across the smallest diameter, and the medial wall thickness between the internal and external elastic lamina of two sides of muscular arteries (M1 and M2) were measured. The percentage of wall thickness was calculated as follows: % wall thickness = (M1 + M2)/D × 100 (H&E staining, × 400).
Mentions: Lung tissue was fixed with 10% buffered formalin with gentle perfusion through the trachea for 24 hr and then embedded in paraffin. Three µm-thick sections were stained with Victoria blue to evaluate histopathologic changes of pulmonary blood vessels. More than 20 images of pulmonary arterioles (50-160 µm diameters) per tissue section at a magnification of 400 × were captured using a microscopic digital camera and analyzed using an image analysis program (analySIS, Olympus Soft Imaging Solutions, Singapore). The external diameter (D), across the smallest diameter, and the medial wall thickness between the internal and external elastic lamina of two sides of muscular arteries (M1 and M2) were measured. The percentage of wall thickness was calculated as follows: % wall thickness = (M1 + M2)/D × 100 (Fig. 1). In addition, the number of muscular arteries accompanied by respiratory bronchioli and present in alveolar wall were counted. A total of 20 randomly selected microscopic fields per tissue section at a magnification (200 ×) were assessed.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, Ewha Womans University, Seoul, Korea.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus