摘要
Objectives: Systemic left-to-right shunting causes pulmonary arteriopathy, leading to progressive cardiopulmonary failure and a poor prognosis. In this study, we examined the extraglycemic effect of a synthetic glucagon-like peptide, exendin-4, on pulmonary arteriopathy regression and cardiopulmonary function in nondiabetic rats. Methods: Pulmonary hypertension (PH) was induced by monocrotaline (60 mg/kg, subcutaneous) injection followed by the creation of an aortocaval fistula. After 4 weeks, exendin-4 (1 μg/kg/day) was administered intraperitoneally for 3 consecutive weeks, followed by an assessment of cardiopulmonary function, pulmonary artery vasoreactivity, tissue and blood biochemistry, and lung histology. Results: Exendin-4 significantly reduced right ventricle mass and pulmonary artery pressure, which improved right ventricle function and the survival rate in rats with PH. Tissue and blood interleukin-1β levels decreased, whereas pulmonary artery cyclic adenosine monophosphate levels were restored by exendin-4. Smooth muscle-myosin heavy chain-II and α-smooth muscle actin protein levels increased in the pulmonary arteries of exendin-4-treated rats. Histology showed that exendin-4 decreased the main and intra-acinar pulmonary artery medial thickness. Conclusions: Exendin-4 treatment improved pulmonary artery function in flow-induced PH via its direct vasoactive properties, anti-inflammatory effects, and vascular smooth muscle cell phenotypic modulation. Mitigation of pulmonary arteriopathy further potentiated right ventricle performance and reduced overall mortality. These responses were associated with suppressed expression and activity of interleukin-1β and its downstream signaling molecules. Glucagon-like peptide analogs may possess pleiotropic therapeutic potential in flow-induced PH.
| 原文 | English |
|---|---|
| 頁（從 - 到） | 1661-1669.e4 |
| 期刊 | Journal of Thoracic and Cardiovascular Surgery |
| 卷 | 155 |
| 發行號 | 4 |
| DOIs | |
| 出版狀態 | Published - 2018 四月 |
指紋
All Science Journal Classification (ASJC) codes
- Surgery
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine
引用此文
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Exendin-4 improves cardiovascular function and survival in flow-induced pulmonary hypertension. / Roan, Jun Neng; Hsu, Chih Hsin; Fang, Shih Yuan; Tsai, Hung Wen; Luo, Chwan Yau; Huang, Chien Chi; Lam, Chen Fuh.
於: Journal of Thoracic and Cardiovascular Surgery, 卷 155, 編號 4, 04.2018, p. 1661-1669.e4.研究成果: Article
TY - JOUR
T1 - Exendin-4 improves cardiovascular function and survival in flow-induced pulmonary hypertension
AU - Roan, Jun Neng
AU - Hsu, Chih Hsin
AU - Fang, Shih Yuan
AU - Tsai, Hung Wen
AU - Luo, Chwan Yau
AU - Huang, Chien Chi
AU - Lam, Chen Fuh
PY - 2018/4
Y1 - 2018/4
N2 - Objectives: Systemic left-to-right shunting causes pulmonary arteriopathy, leading to progressive cardiopulmonary failure and a poor prognosis. In this study, we examined the extraglycemic effect of a synthetic glucagon-like peptide, exendin-4, on pulmonary arteriopathy regression and cardiopulmonary function in nondiabetic rats. Methods: Pulmonary hypertension (PH) was induced by monocrotaline (60 mg/kg, subcutaneous) injection followed by the creation of an aortocaval fistula. After 4 weeks, exendin-4 (1 μg/kg/day) was administered intraperitoneally for 3 consecutive weeks, followed by an assessment of cardiopulmonary function, pulmonary artery vasoreactivity, tissue and blood biochemistry, and lung histology. Results: Exendin-4 significantly reduced right ventricle mass and pulmonary artery pressure, which improved right ventricle function and the survival rate in rats with PH. Tissue and blood interleukin-1β levels decreased, whereas pulmonary artery cyclic adenosine monophosphate levels were restored by exendin-4. Smooth muscle-myosin heavy chain-II and α-smooth muscle actin protein levels increased in the pulmonary arteries of exendin-4-treated rats. Histology showed that exendin-4 decreased the main and intra-acinar pulmonary artery medial thickness. Conclusions: Exendin-4 treatment improved pulmonary artery function in flow-induced PH via its direct vasoactive properties, anti-inflammatory effects, and vascular smooth muscle cell phenotypic modulation. Mitigation of pulmonary arteriopathy further potentiated right ventricle performance and reduced overall mortality. These responses were associated with suppressed expression and activity of interleukin-1β and its downstream signaling molecules. Glucagon-like peptide analogs may possess pleiotropic therapeutic potential in flow-induced PH.
AB - Objectives: Systemic left-to-right shunting causes pulmonary arteriopathy, leading to progressive cardiopulmonary failure and a poor prognosis. In this study, we examined the extraglycemic effect of a synthetic glucagon-like peptide, exendin-4, on pulmonary arteriopathy regression and cardiopulmonary function in nondiabetic rats. Methods: Pulmonary hypertension (PH) was induced by monocrotaline (60 mg/kg, subcutaneous) injection followed by the creation of an aortocaval fistula. After 4 weeks, exendin-4 (1 μg/kg/day) was administered intraperitoneally for 3 consecutive weeks, followed by an assessment of cardiopulmonary function, pulmonary artery vasoreactivity, tissue and blood biochemistry, and lung histology. Results: Exendin-4 significantly reduced right ventricle mass and pulmonary artery pressure, which improved right ventricle function and the survival rate in rats with PH. Tissue and blood interleukin-1β levels decreased, whereas pulmonary artery cyclic adenosine monophosphate levels were restored by exendin-4. Smooth muscle-myosin heavy chain-II and α-smooth muscle actin protein levels increased in the pulmonary arteries of exendin-4-treated rats. Histology showed that exendin-4 decreased the main and intra-acinar pulmonary artery medial thickness. Conclusions: Exendin-4 treatment improved pulmonary artery function in flow-induced PH via its direct vasoactive properties, anti-inflammatory effects, and vascular smooth muscle cell phenotypic modulation. Mitigation of pulmonary arteriopathy further potentiated right ventricle performance and reduced overall mortality. These responses were associated with suppressed expression and activity of interleukin-1β and its downstream signaling molecules. Glucagon-like peptide analogs may possess pleiotropic therapeutic potential in flow-induced PH.
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UR - http://www.scopus.com/inward/citedby.url?scp=85039444761&partnerID=8YFLogxK
U2 - 10.1016/j.jtcvs.2017.10.085
DO - 10.1016/j.jtcvs.2017.10.085
M3 - Article
C2 - 29249493
AN - SCOPUS:85039444761
VL - 155
SP - 1661-1669.e4
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
SN - 0022-5223
IS - 4
ER -