Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model

We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), grou...

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Main Authors: Cheuk-Kwan Sun, Yen-Yi Zhen, Hung-I Lu, Pei-Hsun Sung, Li-Teh Chang, Tzu-Hsien Tsai, Jiunn-Jye Sheu, Yung-Lung Chen, Sarah Chua, Hsueh-Wen Chang, Yi-Ling Chen, Fan-Yen Lee, Hon-Kan Yip
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2014/316214
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author Cheuk-Kwan Sun
Yen-Yi Zhen
Hung-I Lu
Pei-Hsun Sung
Li-Teh Chang
Tzu-Hsien Tsai
Jiunn-Jye Sheu
Yung-Lung Chen
Sarah Chua
Hsueh-Wen Chang
Yi-Ling Chen
Fan-Yen Lee
Hon-Kan Yip
author_facet Cheuk-Kwan Sun
Yen-Yi Zhen
Hung-I Lu
Pei-Hsun Sung
Li-Teh Chang
Tzu-Hsien Tsai
Jiunn-Jye Sheu
Yung-Lung Chen
Sarah Chua
Hsueh-Wen Chang
Yi-Ling Chen
Fan-Yen Lee
Hon-Kan Yip
author_sort Cheuk-Kwan Sun
collection DOAJ
description We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.
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spelling doaj-art-c7ca4996bc854eadbcd9f20aaa29d5a22025-02-03T01:02:33ZengWileyStem Cells International1687-966X1687-96782014-01-01201410.1155/2014/316214316214Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine ModelCheuk-Kwan Sun0Yen-Yi Zhen1Hung-I Lu2Pei-Hsun Sung3Li-Teh Chang4Tzu-Hsien Tsai5Jiunn-Jye Sheu6Yung-Lung Chen7Sarah Chua8Hsueh-Wen Chang9Yi-Ling Chen10Fan-Yen Lee11Hon-Kan Yip12Department of Emergency Medicine, E-Da Hospital, I-Shou University College of Medicine, Kaohsiung 82445, TaiwanDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanBasic Science, Nursing Department, Meiho Institute of Technology, Pingtung 91202, TaiwanDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, TaiwanDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanWe tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.http://dx.doi.org/10.1155/2014/316214
spellingShingle Cheuk-Kwan Sun
Yen-Yi Zhen
Hung-I Lu
Pei-Hsun Sung
Li-Teh Chang
Tzu-Hsien Tsai
Jiunn-Jye Sheu
Yung-Lung Chen
Sarah Chua
Hsueh-Wen Chang
Yi-Ling Chen
Fan-Yen Lee
Hon-Kan Yip
Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model
Stem Cells International
title Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model
title_full Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model
title_fullStr Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model
title_full_unstemmed Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model
title_short Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model
title_sort reducing trpc1 expression through liposome mediated sirna delivery markedly attenuates hypoxia induced pulmonary arterial hypertension in a murine model
url http://dx.doi.org/10.1155/2014/316214
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