Min-Sun Cho

Ewha Womans University, Sŏul, Seoul, South Korea

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Publications (31)71.54 Total impact

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    ABSTRACT: Pulmonary arterial hypertension (PAH) causes right ventricular failure due to a gradual increase in pulmonary vascular resistance. The purposes of this study were to confirm the engraftment of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) placed in the correct place in the lung and research on changes of hemodynamics, pulmonary pathology, immunomodulation and several gene expressions in monocrotaline (MCT)-induced PAH rat models after hUCB-MSCs transfusion. The rats were grouped as follows: the control (C) group; the M group (MCT 60 mg/kg); the U group (hUCB-MSCs transfusion). They received transfusions via the external jugular vein a week after MCT injection. The mean right ventricular pressure (RVP) was significantly reduced in the U group after the 2 week. The indicators of RV hypertrophy were significantly reduced in the U group at week 4. Reduced medial wall thickness in the pulmonary arteriole was noted in the U group at week 4. Reduced number of intra-acinar muscular pulmonary arteries was observed in the U group after 2 week. Protein expressions such as endothelin (ET)-1, endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 significantly decreased at week 4. The decreased levels of ERA, eNOS and MMP-2 immunoreactivity were noted by immnohistochemical staining. After hUCB-MSCs were administered, there were the improvement of RVH and mean RVP. Reductions in several protein expressions and immunomodulation were also detected. It is suggested that hUCB-MSCs may be a promising therapeutic option for PAH. Graphical Abstract
    Journal of Korean medical science 05/2015; 30(5):576-85. DOI:10.3346/jkms.2015.30.5.576
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    05/2015; 49(3):270-3. DOI:10.4132/jptm.2015.04.01
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    ABSTRACT: Although altered levels of adiponectin have been reported as a potential risk factor in colorectal cancer (CRC), the importance of the role played by adiponectin in colorectal carcinogenesis has not been established. We sought to examine the expression pattern of adiponectin and adiponectin receptors (AdipoRs) in the normal-adenoma-carcinoma sequence and to assess the implications of adiponectin in colorectal carcinogenesis.
    BMC Cancer 11/2014; 14(1):811. DOI:10.1186/1471-2407-14-811
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    ABSTRACT: BACKGROUND. One hundred forty nine stromal nodules (SNs) from transurethral resection of benign prostatic hyperplasia specimens in 39 patients (57-85 years with mean of 70.9) were investigated to characterize the SNs and to outline the etiopathogenesis of solitary fibrous tumors (SFTs) and gastrointestinal stromal tumors (GISTs) of prostate by immunohistochemistry performed on tissue microarray sections. METHODS. Antibodies used included smooth muscle actin, desmin, vimentin, and S-100 protein for subtyping, vascular endothelial growth factor, insulin-like growth factor-1, fibroblast growth factor, and TGF-beta as growth factors; CD133, c-KIT, CD34, and CD44 as stem cell markers; and estrogen (ER), progesterone (PR), and androgen receptor (AR) as hormone receptors. RESULTS. SNs were classified into four subtypes: (1) immature mesenchymal (n = 7, 4.7%); (2) fibroblastic (n = 74, 49.7%); (3) fibromuscular (n = 53, 35.6%); and (4) smooth muscular (n = 15, 10.1%) types. There were linear trends of the expression of all growth factors (VEGF, IGF-1, FGF, TGF-beta), but only CD44 stem cell marker and AR hormone receptor as maturation progressed from immature mesenchymal to smooth muscular type (P-trend < 0.05). S-100, c-KIT, and ER were not expressed in any types of SNs. CD34 was positive in 55% of the SNs (82/149). CONCLUSIONS. The data suggest that AR and growth factors are important factors for maturation of SNs, but not influenced by the administration of 5-alpha reductase inhibitor (5ARI). Although the cells comprising the SNs seem to be not associated with the origin of prostatic GISTs, there is a possibility of a tentative link of SFTs arising from SNs of the prostate. (C) 2014 Wiley Periodicals, Inc.
    The Prostate 10/2014; 74(14). DOI:10.1002/pros.22859
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    ABSTRACT: Obstructive jaundice caused by tuberculous lymphadenitis is a rare manifestation of tuberculosis (TB), with 15 cases having been reported in Korea. We experienced a case of obstructive jaundice caused by pericholedochal tuberculous lymphadenitis in a 30-year-old man. The patient's initial serum total bilirubin level was 21.1 mg/dL. Abdominal computed tomography revealed narrowing of the bile duct by a conglomerated soft-tissue mass involving the main portal vein. Abrupt obstruction of the common bile duct was observed on cholangiography. Pathologic analysis of a ultrasonography-guided biopsy sample revealed chronic granulomatous inflammation, and an endoscopic examination revealed esophageal varices and active duodenal ulceration, the pathology of which was chronic noncaseating granulomatous inflammation. Hepaticojejunostomy was performed and pathologic analysis of the conglomerated soft-tissue mass revealed chronic granulomatous inflammation with caseation of the lymph nodes. Tuberculous lymphadenitis should be considered in patients presenting with obstructive jaundice in an endemic area.
    06/2014; 20(2):208-13. DOI:10.3350/cmh.2014.20.2.208
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    ABSTRACT: Objectives Our study examines thyroid transcription factor 1 (TTF-1) expression in 40 primary adenoid cystic carcinomas (ACCs) arising in various sites and compares TTF-1 expression between primary and metastatic ACCs in 12 cases with distant metastases. Methods Forty patients with ACCs, including 12 pairs of primary and metastatic ACCs, were evaluated for the immunohistochemical expression of TTF-1 (clone SPT24). In addition, 10 metastatic ACCs to the lung were tested on napsin A and a different TTF-1 antibody (clone 8G7G3) for further evaluation. Results No primary ACCs showed TTF-1 immunoreactivity (clone SPT24). TTF-1 was positive in five (41.7%) of 12 metastatic ACCs; all five cases were found only in the lung and comprised five (50.0%) of 10 cases. In all positive cases, staining was focal and detected only in the cribriform histologic subtype. Staining patterns using both antibodies (both SPT24 and 8G7G3) were very similar, and TTF-1-positive tumor cells were also positive for napsin A. Extrapulmonary ACCs were all negative for TTF-1 regardless of origination and metastasis. Conclusions TTF-1- and napsin A-positive ACCs in the lung should not be considered primary ACCs because TTF-1 and napsin A can be expressed in metastatic ACCs of the lung.
    American Journal of Clinical Pathology 05/2014; 141(5):712-7. DOI:10.1309/AJCPB0YIY6LQLQTG
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    ABSTRACT: Wegener's granulomatosis (WG) is a systemic vasculitis affecting small and medium-sized vessels with granulomatous formation. Though it is known for respiratory tract and kidney involvement, neurologic manifestation has been also reported. Herein we report a patient who suffered pansinusitis with multiple lower cranial nerve palsies but reached remission by immunosuppressant after the diagnosis of WG. A 54-yr-old female visited with headache, hearing difficulty, and progressive bulbar symptoms. She experienced endoscopic sinus surgeries due to refractory sinusitis. Neurologic examination revealed multiple lower cranial nerve palsies. Vasculitic markers showed no abnormality. Nasal biopsy revealed granulomatous inflammation and vasculitis involving small vessels. Given cyclophosphamide and prednisolone, her symptoms were prominently improved. WG should be considered in the patient with multiple cranial nerve palsies, especially those with paranasal sinus disease. Because WG can be lethal if delayed in treatment, prompt immunosuppressant is warranted after the diagnostic tissue biopsy.
    Journal of Korean medical science 11/2013; 28(11):1690-1696. DOI:10.3346/jkms.2013.28.11.1690
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    ABSTRACT: Apoptotic cell instillation after bleomycin induces persistent HGF production and protects from pulmonary fibrosis, but the underlying mechanism remains unclear. We investigated immediate and prolonged effects of in vivo instillation of apoptotic cells into bleomycin-stimulated mouse lungs (2 days old) on COX-2 expression in lung tissue and alveolar macrophages and PGE2 production in BALF. Furthermore, functional interaction between these molecules and HGF, following apoptotic cell instillation in a bleomycin-induced lung fibrosis model, was assessed. Apoptotic cell instillation results in enhanced immediate and prolonged expression of COX-2 and PGE2 when compared with those from bleomycin-only-treated mice. Coadministration of the COX-2-selective inhibitor NS398 or the selective PGE2R EP2 inhibitor AH6809 inhibited the increase in HGF production. Inhibition of HGF signaling using PHA-665752 inhibited increases in COX-2 and PGE2. Long-term inhibition of COX-2, PGE2, or HGF reversed the reduction of TGF-β, apoptotic and MPO activities, protein levels, and hydroxyproline contents. Up-regulation of COX-2/PGE2 and HGF through a positive-feedback loop may be an important mechanism whereby apoptotic cell instillation exerts the net results of anti-inflammatory, antiapoptotic, and antifibrotic action.
    Journal of leukocyte biology 08/2013; 94(5). DOI:10.1189/jlb.0513255
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    ABSTRACT: Tumor necrosis factor (TNF)-α is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-α antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-α, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)2, and tissue inhibitor of matrix metalloproteinase (TIMP). The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intra-acinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-α, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). Infliximab administration induced early changes in pathological findings and expression levels of TNF-α, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.
    Korean Journal of Pediatrics 03/2013; 56(3):116-24. DOI:10.3345/kjp.2013.56.3.116
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    ABSTRACT: Sunitinib an inhibitor of the vascular endothelial growth factor receptor, is highly effective against renal cell carcinoma and is now widely used in patients with metastatic disease. Gastroesophageal reflux disease (GERD) is rarely reported as a side effect of sunitinib. We report two cases of GERD with upper gastrointestinal bleeding related to sunitinib administration. Both cases responded well to conservative management. Microscopic findings in both cases showed cellular atypia such as hyperchromasia, increases in nuclear size, and multinucleation. The cellular atypia of the squamous mucosa appears to be associated with reparative processes.
    01/2013; 36(1):58. DOI:10.12771/emj.2013.36.1.58
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    ABSTRACT: The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme (ECE)-1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Ninty-four Sprague-Dawley rats were divided into three groups: control (n = 24), MCT (n = 35) and shRNA (n = 35). Four-week survival rate in the shRNA group was significantly increased compared to that in the MCT group. The shRNA group showed a significant improvement of right ventricular (RV) pressure compared with the MCT group. The MCT and shRNA groups also showed an increase in RV/(left ventricle + septum) ratio and lung/body weight. Plasma endothelin (ET)-1 concentrations in the shRNA group were lower than those in the MCT group. Medial wall thickness of pulmonary arterioles were increased after MCT injection and was significantly decreased in the shRNA group. The number of intra-acinar muscular pulmonary arteries was decreased in the shRNA group. The mRNA expressions of ET-1 and ET receptor A (ET(A)) were significantly decreased in the shRNA group in week 4. The protein levels of ET(A) were decreased in the shRNA group in week 2. The protein levels of tumor necrosis factor-α and vascular endothelial growth factor were decreased in the shRNA group in week 4. In conclusion, the gene silencing with lentiviral vector targeting ECE-1 could be effective against hemodynamic, histopathological and gene expression changes in pulmonary hypertension.
    Journal of Korean medical science 12/2012; 27(12):1507-16. DOI:10.3346/jkms.2012.27.12.1507
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    ABSTRACT: The renin angiotensin system seems to play an important role in the development of cardiac and vascular hypertrophy in hypertension. The changes in pathology, and gene expressions of the angiotensin II receptor type 1A (ATIA) and angiotensin converting enzyme (ACE) were investigated in order to explore the effects of losartan in spontaneously hypertensive rat (SHR) models. Twelve week-old male Wistar rats were grouped as follows: control (C) group, hypertension (H) group, and losartan (L) group in which SHR was treated with losartan (10 mg/kg/day). Western blot and reverse transcription-polymerase chain reaction analysis regarding seven genes such as endothelin-1, ACE, ATIA, neutrophil cytosolic factor, brain natriuretic peptide, troponin I, endothelial nitric oxide synthase were performed. Systolic blood pressure was significantly decreased in the L group compared with the H group in weeks 3 and 5. ACE and ATIA proteins in the L group were lower than H group in week 5. Losartan reduced blood pressure, cardiac hypertrophy and protein expressions of ACE and ATIA. Changes of protein expressions were more sensitive than changes in pathology. Further study is needed for the differing doses of losartan in SHR models.
    Korean Circulation Journal 11/2012; 42(11):761-8. DOI:10.4070/kcj.2012.42.11.761
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    Hyeon Kook Lee, Min-Sun Cho, Tae Hun Kim
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    ABSTRACT: BACKGROUND: Mucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis. METHODS: The expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining. RESULTS: For gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05). CONCLUSIONS: MUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression.
    World Journal of Surgical Oncology 10/2012; 10(1):224. DOI:10.1186/1477-7819-10-224
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    ABSTRACT: Ischemic colitis is a rare complication of interferon administration. Only 9 cases in 6 reports have been described to-date. This report describes a case of ischemic colitis during pegylated interferon and ribavirin treatment for chronic hepatitis C, and includes a review of the relevant literature. A 48-year-old woman was treated with pegylated interferon α-2a and ribavirin for chronic hepatitis C, genotype Ib. After 19 wk of treatment, the patient complained of severe afebrile abdominal pain with hematochezia. Vital signs were stable and serum white blood cell count was within the normal range. Abdominal computed tomography showed diffuse colonic wall thickening from the splenic flexure to the proximal sigmoid colon, which is the most vulnerable area for the development of ischemic colitis. Colonoscopy revealed an acute mucosal hyperemic change, with edema and ulcerations extending from the proximal descending colon to the sigmoid colon. Colonic mucosal biopsy revealed acute exudative colitis. Polymerase chain reaction and culture for Mycobacterium tuberculosis were negative and the cultures for cytomegalovirus, Salmonella and Shigella species were negative. After discontinuation of interferon and ribavirin therapy, abdominal pain and hematochezia subsided and, following colonoscopy showed improvement of the mucosal ulcerations. Ischemic colitis cases during interferon therapy in patients with chronic hepatitis C reported so far have all involved the descending colon. Ischemic colitis is a rarely encountered complication of interferon administration in patients with chronic hepatitis C and should be considered when a patient complains of abdominal pain and hematochezia.
    World Journal of Gastroenterology 08/2012; 18(31):4233-6. DOI:10.3748/wjg.v18.i31.4233
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    ABSTRACT: Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment.
    Toxicology and Applied Pharmacology 06/2012; 263(1):61-72. DOI:10.1016/j.taap.2012.05.024
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    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.
    Journal of Korean medical science 06/2012; 27(6):605-13. DOI:10.3346/jkms.2012.27.6.605
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    ABSTRACT: Apoptotic cell clearance by macrophages and neighbouring tissue cells induces hepatocyte growth factor (HGF) secretion. HGF plays a key role in alveolar epithelial regeneration and reconstruction after lung injury. Direct in vivo exposure to apoptotic cells enhances HGF production, resulting in attenuation of pulmonary injury. We investigated the direct effect of in vivo exposure to apoptotic cells in bleomycin-stimulated lungs (2 days old) on HGF induction. Furthermore, sequential changes of bleomycin-induced HGF production following apoptotic cell instillation related to the changes in inflammatory and fibrotic responses were assessed. At 2 h after apoptotic cell instillation into bleomycin-stimulated lungs, the levels of HGF mRNA and protein production, and apoptotic cell clearance by alveolar macrophages were enhanced. Furthermore, HGF induction persistently increased following apoptotic cell instillation up to 21 days after bleomycin treatment. Apoptotic cell instillation attenuated bleomycin-induced pro-inflammatory mediator production, inflammatory cell recruitment and total protein levels. Apoptotic cell instillation also induced antiapoptotic and antifibrotic effects. These anti-inflammatory and antiapoptotic effects could be reversed by co-administration of HGF-neutralising antibody. These findings indicate that in vivo exposure to apoptotic cells enhances transcriptional HGF production in bleomycin-stimulated lungs, resulting in attenuation of lung injury and fibrosis.
    European Respiratory Journal 03/2012; 40(2):424-35. DOI:10.1183/09031936.00096711
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    ABSTRACT: Mer signaling participates in a novel inhibitory pathway in TLR activation. The purpose of the present study was to examine the role of Mer signaling in the down-regulation of TLR4 activation-driven immune responses in mice, i.t.-treated with LPS, using the specific Mer-blocking antibody. At 4 h and 24 h after LPS treatment, expression of Mer protein in alveolar macrophages and lung tissue decreased, sMer in BALF increased significantly, and Mer activation increased. Pretreatment with anti-Mer antibody did not influence the protein levels of Mer and sMer levels. Anti-Mer antibody significantly reduced LPS-induced Mer activation, phosphorylation of Akt and FAK, STAT1 activation, and expression of SOCS1 and -3. Anti-Mer antibody enhanced LPS-induced inflammatory responses, including activation of the NF-κB pathway; the production of TNF-α, IL-1β, and MIP-2 and MMP-9 activity; and accumulation of inflammatory cells and the total protein levels in BALF. These results indicate that Mer plays as an intrinsic feedback inhibitor of the TLR4- and inflammatory mediator-driven immune responses during acute lung injury.
    Journal of leukocyte biology 03/2012; 91(6):921-32. DOI:10.1189/jlb.0611289
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    ABSTRACT: Simvastatin's properties are suggestive of a potential pathophysiologic role in pulmonary hypertension. The objectives of this study were to investigate changes of pulmonary pathology and gene expressions, including endothelin (ET)-1, endothelin receptor A (ERA), inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), matrix metalloproteinase (MMP) 2, tissue inhibitor of matrix metalloproteinases (TIMP) and caspase 3, and to evaluate the effect of simvastatin on monocrotaline (M)-induced pulmonary hypertension. Six week old male Sprague-Dawley rats were treated, as follows: control group, subcutaneous (sc) injection of saline; M group, sc injection of M (60 mg/kg); and simvastatin group, sc injection of M (60 mg/kg) plus 10 mg/kg/day simvastatin orally. On day 28, right ventricular hypertrophy (RVH) significantly decreased in the simvastatin group compared to the M group. Similarly, right ventricular pressure significantly decreased in the simvastatin group on day 28. From day 7, the ratio of medial thickening of the pulmonary artery was significantly increased in the M group, but there was no significant change in the simvastatin group. The number of muscular pulmonary arterioles was significantly reduced in the simvastatin group. On day 5, gene expressions of ET-1, ERA, NOS2, NOS3, MMP and TIMP significantly decreased in the simvastatin group. Administration of simvastatin exerted weak inhibitory effects on RVH and on the number of muscular pulmonary arterioles, during the development of M-induced pulmonary hypertension in rats. Simvastatin decreased gene expressions on day 5.
    Korean Circulation Journal 09/2011; 41(9):518-27. DOI:10.4070/kcj.2011.41.9.518
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    ABSTRACT: Endothelin (ET)-1, a potent endothelium-derived vasoconstrictor peptide, has a potential pathophysiologic role in pulmonary hypertension. Bosentan, a dual ET receptor (ET(A)/ET(B)) antagonist, is efficacious in treatment of pulmonary hypertension. The objectives of this study were to investigate the expression of ET-1 and ET receptor A (ERA) genes and to evaluate the effect of bosentan in monocrotaline (MCT)-induced pulmonary hypertension. Four-week-old male Sprague-Dawley rats were treated as follows: control (n=36), subcutaneous (sc) injection of saline; MCT (n=36), sc injection of MCT (60 mg/kg); and bosentan (n=36), sc injection of MCT (60 mg/kg) plus 25 mg/kg/day bosentan orally. Serum ET-1 concentrations in the MCT group were higher than the control group on day 28 and 42. Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan group on day 28 and 42. In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on day 14, 28 and 42. The levels of ET-1 and ERA gene expression were significantly increased in the MCT group compared with control group on day 5, and bosentan decreased the expression of ET-1 on day 5. ET-1 contributes to the progression of cardiopulmonary pathology in rats with MCT-induced pulmonary hypertension. Administration of bosentan reduced ET-1 gene expression in MCT-induced pulmonary hypertension in rats.
    Korean Circulation Journal 09/2010; 40(9):459-64. DOI:10.4070/kcj.2010.40.9.459