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Honkan Yip - One of the best experts on this subject based on the ideXlab platform.
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entresto therapy effectively protects heart and lung against transverse Aortic Constriction induced cardiopulmonary syndrome injury in rat
2018Co-Authors: Mengshen Tong, Shengying Chung, Peihsun Sung, Fanyen Lee, Kuanhung Chen, John Y Chiang, Honkan YipAbstract:This study tested the hypothesis that entresto therapy effectively protected heart and lung against cardiopulmonary syndrome (CPS) caused by transverse Aortic Constriction (TAC) in rat. Adult-Male SD rats (n = 36) were equally categorized into group 1 [sham-operated control (SC)], group 2 [SC + enalapril (7 mg/kg/day) since day-28 after TAC induction], group 3 [SC + entresto (30 mg/kg/day) since day-14 after TAC induction], group 4 (TAC only), group 5 (TAC + enalapril) and group 6 (TAC + entresto) and euthanized at day 60 after TAC induction. By day 60, the left-ventricular (LV) ejection fraction was significantly lower in group 4 than in other groups and significantly lower in groups 5 and 6 than in groups 1 to 3, whereas the ratios of heart and lung weights to tibial-length as well as the right-ventricular-systolic blood pressure exhibited an opposite pattern among the groups (all P<0.001). The sarcomere-length (SL), LV fibrotic area, cardiomyocyte size, and lung injury score were highest in group 4, lowest in groups 1 to 3 and significantly lower in group 6 than in group 5 (all P<0.0001). The protein expressions of fibrotic (Smad3/TGF-β), apoptotic (mitochondrial-Bax/cleaved-caspase3/PARP) and DNA-damaged (γ-H2AX) markers in lung and LV myocardium as well as oxidative (NOX-1/NOX2/oxidized protein) in LV myocardium exhibited an identical pattern of SL (all P<0.0001). The protein expressions of pressure/volume overload (BNP/MHC-β) mitochondrial-damaged (cytosolic cytochrome-C) of LV myocardium exhibited an identical pattern of SL (all P<0.001). In conclusion, Entresto is non-inferior to enalapril for protecting the heart-lung against CPS.
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exendin 4 therapy still offered an additional benefit on reducing transverse Aortic Constriction induced cardiac hypertrophy caused myocardial damage in dpp 4 deficient rats
2016Co-Authors: Shengying Chung, Sarah Chua, Yunglung Chen, Jiunnjye Sheu, Yiling Chen, Chufeng Liu, Yenyi Zhen, Teinhung Huang, Mengwei Chang, Honkan YipAbstract:Inhibition of dipeptidyl peptidase-IV (DPP-4) enzyme activity has been revealed to protect myocardium from ischemia-reperfusion through enhancing the endogenous glucagon-like peptide-1 (GLP-1) level. However, whether exogenous supply of exendin-4, an analogue of GLP-1, would still offer benefit for protecting myocardial damage from trans-Aortic Constriction (TAC)-induced hypertrophic cardiomyopathy in preexistence of DPP-4 deficiency (DPP-4(D)) remained unclear. Male-adult (DPP-4(D)) rats (n = 32) were randomized into group 1 [sham control (SC)], group 2 (DPP-4(D) + TAC), group 3 [DPP-4(D) + TAC + exendin-4 10 µg/day], and group 4 [DPP-4(D) + TAC + exendin-4 10 µg + exendin-9-39 10 µg/day]. The rats were sacrificed by day 60 after last echocardiographic examination. By day 60 after TAC, left ventricular ejection fraction (LVEF) (%) was highest in group 1 and lowest in group 2, and significantly lower in group 4 than that in group 3 (all p < 0.001). The protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), inflammatory (MMP-9, TNF-α, NF-κB), apoptotic (Bax, cleaved caspase 3 and PARP), fibrotic (TGF-β, Smad3), heart failure (BNP, β-MHC), DNA damaged (γ-H2AX) and ischemic stress (p-P38, p-Akt, p53, ATM) biomarkers showed an opposite pattern of LVEF among the four groups (all p < 0.03). Fibrotic area (by Masson's trichrome, Sirius red), and cellular expressions of DNA-damaged markers (Ki-67+, γ-H2AX+, CD90+/53BP1+) displayed an identical pattern, whereas cellular expressions of angiogenesis (CD31+, α-SMA+) and sarcomere length exhibited an opposite pattern compared to that of oxidative stress among the four groups (all p < 0.001). Take altogether, Exendin-4 effectively suppressed TAC-induced pathological cardiac hypertrophy in DPP-4(D) rat.
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abstract 9851 benefit of antioxidant peptide ss 31 treatment in attenuating transverse Aortic Constriction induced pulmonary arterial hypertension in mice
2015Co-Authors: Shengying Chung, Sarah Chua, Tzuhsien Tsai, Peihsun Sung, Yunglung Chen, Steve Leu, Jiunnjye Sheu, Honkan YipAbstract:Introduction: We investigated the effect of mitochondria-targeted antioxidant peptide SS-31 on transthoracic Aortic Constriction (TAC)-induced pulmonary arterial hypertension (PAH) in mice. Methods...
Shengying Chung - One of the best experts on this subject based on the ideXlab platform.
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entresto therapy effectively protects heart and lung against transverse Aortic Constriction induced cardiopulmonary syndrome injury in rat
2018Co-Authors: Mengshen Tong, Shengying Chung, Peihsun Sung, Fanyen Lee, Kuanhung Chen, John Y Chiang, Honkan YipAbstract:This study tested the hypothesis that entresto therapy effectively protected heart and lung against cardiopulmonary syndrome (CPS) caused by transverse Aortic Constriction (TAC) in rat. Adult-Male SD rats (n = 36) were equally categorized into group 1 [sham-operated control (SC)], group 2 [SC + enalapril (7 mg/kg/day) since day-28 after TAC induction], group 3 [SC + entresto (30 mg/kg/day) since day-14 after TAC induction], group 4 (TAC only), group 5 (TAC + enalapril) and group 6 (TAC + entresto) and euthanized at day 60 after TAC induction. By day 60, the left-ventricular (LV) ejection fraction was significantly lower in group 4 than in other groups and significantly lower in groups 5 and 6 than in groups 1 to 3, whereas the ratios of heart and lung weights to tibial-length as well as the right-ventricular-systolic blood pressure exhibited an opposite pattern among the groups (all P<0.001). The sarcomere-length (SL), LV fibrotic area, cardiomyocyte size, and lung injury score were highest in group 4, lowest in groups 1 to 3 and significantly lower in group 6 than in group 5 (all P<0.0001). The protein expressions of fibrotic (Smad3/TGF-β), apoptotic (mitochondrial-Bax/cleaved-caspase3/PARP) and DNA-damaged (γ-H2AX) markers in lung and LV myocardium as well as oxidative (NOX-1/NOX2/oxidized protein) in LV myocardium exhibited an identical pattern of SL (all P<0.0001). The protein expressions of pressure/volume overload (BNP/MHC-β) mitochondrial-damaged (cytosolic cytochrome-C) of LV myocardium exhibited an identical pattern of SL (all P<0.001). In conclusion, Entresto is non-inferior to enalapril for protecting the heart-lung against CPS.
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administration of antioxidant peptide ss 31 attenuates transverse Aortic Constriction induced pulmonary arterial hypertension in mice
2016Co-Authors: Tienhung Huang, Shengying Chung, Sarah Chua, Peihsun Sung, Yunglung Chen, Hanyan Chai, Chufeng Liu, Cheukkwan Sun, Hsuehwen Chang, Yenyi ZhenAbstract:Antioxidant peptide SS-31 is a class of cell-permeable small peptides, which selectively resides on the inner mitochondrial membrane and possesses intrinsic mitochondrial protective capacities. In this study we investigated the therapeutic effects of antioxidant peptide SS-31 on transverse Aortic Constriction (TAC)-induced pulmonary arterial hypertension (PAH) in a murine model. Adult male mice were divided into 3 groups: sham-operated mice, TAC mice, and TAC+SS-31 mice that underwent TAC surgery and received SS-31 (2 mg/d, ip) for 60 d. The right ventricular systolic blood pressure (RVSBP) was measured on d 60 prior to sacrificing the mice; then their right heart and lung tissues were collected for histological and biochemical examinations. Lung injury scores were defined by the increased crowded area and decreased number of alveolar sacs. TAC mice showed significantly higher RVSBP compared with sham-operated mice, the elevation was substantially suppressed in TAC+SS-31 mice. The same pattern of changes was found in pulmonary levels of oxidative stress proteins (NOX-1/NOX-2/oxidized proteins), cytosolic cytochrome c, biomarkers related to inflammation (MMP-9/TNF-α/iNOS), calcium overload index (TRPC1, 2, 4, 6), apoptosis (mitochondrial BAX, cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxic (HIF-1α), DNA damage (γ-H2AX) and endothelial function (eNOS/ET-1R), as well as in lung injury score, number of muscularized vessels in lungs, number of TRPC1+ and HIF-1α+ cells in pulmonary artery, and number of γ-H2AX+ and Ki-67+ cells in lung parenchyma. An opposite pattern of changes was observed in pulmonary anti-fibrotic markers (Smad1/5, BMP-2), number of small vessels, and number of alveolar sacs. In contrast, the levels of antioxidant proteins (HO-1/NQO-1/GR/GPx) in lung parenchyma were progressively and significantly increased from sham-operated mice, TAC mice to TAC+SS-31 mice. Antioxidant peptide SS-31 administration effectively attenuates TAC-induced PAH in mice.
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exendin 4 therapy still offered an additional benefit on reducing transverse Aortic Constriction induced cardiac hypertrophy caused myocardial damage in dpp 4 deficient rats
2016Co-Authors: Shengying Chung, Sarah Chua, Yunglung Chen, Jiunnjye Sheu, Yiling Chen, Chufeng Liu, Yenyi Zhen, Teinhung Huang, Mengwei Chang, Honkan YipAbstract:Inhibition of dipeptidyl peptidase-IV (DPP-4) enzyme activity has been revealed to protect myocardium from ischemia-reperfusion through enhancing the endogenous glucagon-like peptide-1 (GLP-1) level. However, whether exogenous supply of exendin-4, an analogue of GLP-1, would still offer benefit for protecting myocardial damage from trans-Aortic Constriction (TAC)-induced hypertrophic cardiomyopathy in preexistence of DPP-4 deficiency (DPP-4(D)) remained unclear. Male-adult (DPP-4(D)) rats (n = 32) were randomized into group 1 [sham control (SC)], group 2 (DPP-4(D) + TAC), group 3 [DPP-4(D) + TAC + exendin-4 10 µg/day], and group 4 [DPP-4(D) + TAC + exendin-4 10 µg + exendin-9-39 10 µg/day]. The rats were sacrificed by day 60 after last echocardiographic examination. By day 60 after TAC, left ventricular ejection fraction (LVEF) (%) was highest in group 1 and lowest in group 2, and significantly lower in group 4 than that in group 3 (all p < 0.001). The protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), inflammatory (MMP-9, TNF-α, NF-κB), apoptotic (Bax, cleaved caspase 3 and PARP), fibrotic (TGF-β, Smad3), heart failure (BNP, β-MHC), DNA damaged (γ-H2AX) and ischemic stress (p-P38, p-Akt, p53, ATM) biomarkers showed an opposite pattern of LVEF among the four groups (all p < 0.03). Fibrotic area (by Masson's trichrome, Sirius red), and cellular expressions of DNA-damaged markers (Ki-67+, γ-H2AX+, CD90+/53BP1+) displayed an identical pattern, whereas cellular expressions of angiogenesis (CD31+, α-SMA+) and sarcomere length exhibited an opposite pattern compared to that of oxidative stress among the four groups (all p < 0.001). Take altogether, Exendin-4 effectively suppressed TAC-induced pathological cardiac hypertrophy in DPP-4(D) rat.
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abstract 9851 benefit of antioxidant peptide ss 31 treatment in attenuating transverse Aortic Constriction induced pulmonary arterial hypertension in mice
2015Co-Authors: Shengying Chung, Sarah Chua, Tzuhsien Tsai, Peihsun Sung, Yunglung Chen, Steve Leu, Jiunnjye Sheu, Honkan YipAbstract:Introduction: We investigated the effect of mitochondria-targeted antioxidant peptide SS-31 on transthoracic Aortic Constriction (TAC)-induced pulmonary arterial hypertension (PAH) in mice. Methods...
Sarah Chua - One of the best experts on this subject based on the ideXlab platform.
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ss31 therapy effectively protects the heart against transverse Aortic Constriction induced hypertrophic cardiomyopathy damage
2017Co-Authors: Fanyen Lee, Sarah Chua, Peihsun Sung, Jiunnjye Sheu, Christopher Glenn Wallace, Kuanhung Chen, Mengshen Tong, Tienhung Huang, Yiling Chen, Peilin ShaoAbstract:This study tested the hypothesis that SS31 therapy could effectively protect the heart against transverse Aortic Constriction (TAC)-induced hypertrophic cardiomyopathy (HCM) damage. Adult-male B6 mice (n=36) were equally divided into sham-operated control (group 1), TAC only (group 2) and TAC+SS31 (group) (2.0 mg/kg/day by intra-peritoneal administration from day 28 after TAC induction) and euthanized by day 60. In vitro results showed that SS31 markedly suppressed angiotensin-II induced protein expressions of BNP/β-MHC, ATM, p-P38 and P53 and ATP damage in H9C2 cells, and protein expression of pro-collagen-I/CTGF in fibroblasts (all P<0.001). By day 60, left ventricular ejection fraction (LVEF) and sarcomere length were significantly lower in group 2 than groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the LEVDd/LVESd and ratio of heart weight to tibial length showed an opposite pattern to LVEF (all P<0.0001). Microscopic findings of numbers of apoptotic nuclei, inflammatory (CD14+, F4/80+) and oxidative-stress (H2DCFDA+) biomarkers, disorganized score of endocardium, and fibrotic and collagen-deposition areas showed an opposite pattern to LVEF among the three groups (all P<0.0001). The protein expressions of inflammatory (PDGF/TNF-α/NF-κB/COX-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), fibrotic (TGF-β/Smad3) apoptotic (cleaved-caspase-3/cleaved-PARP), pressure/volume overload (BNP/β-MHC), CTGF, mitochondrial-damaged (cytosolic cytochrome-C), p-ERK1/2, p-Akt and PI3K signaling showed an opposite pattern to LVEF among the three groups (all P<0.001). The protein expression of anti-oxidants (HO-1/Nrf2) were significantly progressively increased in groups 1 to 3 (all P<0.001). In conclusion, SS31 therapy effectively protected the heart against TAC-induced damage.
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administration of antioxidant peptide ss 31 attenuates transverse Aortic Constriction induced pulmonary arterial hypertension in mice
2016Co-Authors: Tienhung Huang, Shengying Chung, Sarah Chua, Peihsun Sung, Yunglung Chen, Hanyan Chai, Chufeng Liu, Cheukkwan Sun, Hsuehwen Chang, Yenyi ZhenAbstract:Antioxidant peptide SS-31 is a class of cell-permeable small peptides, which selectively resides on the inner mitochondrial membrane and possesses intrinsic mitochondrial protective capacities. In this study we investigated the therapeutic effects of antioxidant peptide SS-31 on transverse Aortic Constriction (TAC)-induced pulmonary arterial hypertension (PAH) in a murine model. Adult male mice were divided into 3 groups: sham-operated mice, TAC mice, and TAC+SS-31 mice that underwent TAC surgery and received SS-31 (2 mg/d, ip) for 60 d. The right ventricular systolic blood pressure (RVSBP) was measured on d 60 prior to sacrificing the mice; then their right heart and lung tissues were collected for histological and biochemical examinations. Lung injury scores were defined by the increased crowded area and decreased number of alveolar sacs. TAC mice showed significantly higher RVSBP compared with sham-operated mice, the elevation was substantially suppressed in TAC+SS-31 mice. The same pattern of changes was found in pulmonary levels of oxidative stress proteins (NOX-1/NOX-2/oxidized proteins), cytosolic cytochrome c, biomarkers related to inflammation (MMP-9/TNF-α/iNOS), calcium overload index (TRPC1, 2, 4, 6), apoptosis (mitochondrial BAX, cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxic (HIF-1α), DNA damage (γ-H2AX) and endothelial function (eNOS/ET-1R), as well as in lung injury score, number of muscularized vessels in lungs, number of TRPC1+ and HIF-1α+ cells in pulmonary artery, and number of γ-H2AX+ and Ki-67+ cells in lung parenchyma. An opposite pattern of changes was observed in pulmonary anti-fibrotic markers (Smad1/5, BMP-2), number of small vessels, and number of alveolar sacs. In contrast, the levels of antioxidant proteins (HO-1/NQO-1/GR/GPx) in lung parenchyma were progressively and significantly increased from sham-operated mice, TAC mice to TAC+SS-31 mice. Antioxidant peptide SS-31 administration effectively attenuates TAC-induced PAH in mice.
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exendin 4 therapy still offered an additional benefit on reducing transverse Aortic Constriction induced cardiac hypertrophy caused myocardial damage in dpp 4 deficient rats
2016Co-Authors: Shengying Chung, Sarah Chua, Yunglung Chen, Jiunnjye Sheu, Yiling Chen, Chufeng Liu, Yenyi Zhen, Teinhung Huang, Mengwei Chang, Honkan YipAbstract:Inhibition of dipeptidyl peptidase-IV (DPP-4) enzyme activity has been revealed to protect myocardium from ischemia-reperfusion through enhancing the endogenous glucagon-like peptide-1 (GLP-1) level. However, whether exogenous supply of exendin-4, an analogue of GLP-1, would still offer benefit for protecting myocardial damage from trans-Aortic Constriction (TAC)-induced hypertrophic cardiomyopathy in preexistence of DPP-4 deficiency (DPP-4(D)) remained unclear. Male-adult (DPP-4(D)) rats (n = 32) were randomized into group 1 [sham control (SC)], group 2 (DPP-4(D) + TAC), group 3 [DPP-4(D) + TAC + exendin-4 10 µg/day], and group 4 [DPP-4(D) + TAC + exendin-4 10 µg + exendin-9-39 10 µg/day]. The rats were sacrificed by day 60 after last echocardiographic examination. By day 60 after TAC, left ventricular ejection fraction (LVEF) (%) was highest in group 1 and lowest in group 2, and significantly lower in group 4 than that in group 3 (all p < 0.001). The protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), inflammatory (MMP-9, TNF-α, NF-κB), apoptotic (Bax, cleaved caspase 3 and PARP), fibrotic (TGF-β, Smad3), heart failure (BNP, β-MHC), DNA damaged (γ-H2AX) and ischemic stress (p-P38, p-Akt, p53, ATM) biomarkers showed an opposite pattern of LVEF among the four groups (all p < 0.03). Fibrotic area (by Masson's trichrome, Sirius red), and cellular expressions of DNA-damaged markers (Ki-67+, γ-H2AX+, CD90+/53BP1+) displayed an identical pattern, whereas cellular expressions of angiogenesis (CD31+, α-SMA+) and sarcomere length exhibited an opposite pattern compared to that of oxidative stress among the four groups (all p < 0.001). Take altogether, Exendin-4 effectively suppressed TAC-induced pathological cardiac hypertrophy in DPP-4(D) rat.
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abstract 9851 benefit of antioxidant peptide ss 31 treatment in attenuating transverse Aortic Constriction induced pulmonary arterial hypertension in mice
2015Co-Authors: Shengying Chung, Sarah Chua, Tzuhsien Tsai, Peihsun Sung, Yunglung Chen, Steve Leu, Jiunnjye Sheu, Honkan YipAbstract:Introduction: We investigated the effect of mitochondria-targeted antioxidant peptide SS-31 on transthoracic Aortic Constriction (TAC)-induced pulmonary arterial hypertension (PAH) in mice. Methods...
Peihsun Sung - One of the best experts on this subject based on the ideXlab platform.
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entresto therapy effectively protects heart and lung against transverse Aortic Constriction induced cardiopulmonary syndrome injury in rat
2018Co-Authors: Mengshen Tong, Shengying Chung, Peihsun Sung, Fanyen Lee, Kuanhung Chen, John Y Chiang, Honkan YipAbstract:This study tested the hypothesis that entresto therapy effectively protected heart and lung against cardiopulmonary syndrome (CPS) caused by transverse Aortic Constriction (TAC) in rat. Adult-Male SD rats (n = 36) were equally categorized into group 1 [sham-operated control (SC)], group 2 [SC + enalapril (7 mg/kg/day) since day-28 after TAC induction], group 3 [SC + entresto (30 mg/kg/day) since day-14 after TAC induction], group 4 (TAC only), group 5 (TAC + enalapril) and group 6 (TAC + entresto) and euthanized at day 60 after TAC induction. By day 60, the left-ventricular (LV) ejection fraction was significantly lower in group 4 than in other groups and significantly lower in groups 5 and 6 than in groups 1 to 3, whereas the ratios of heart and lung weights to tibial-length as well as the right-ventricular-systolic blood pressure exhibited an opposite pattern among the groups (all P<0.001). The sarcomere-length (SL), LV fibrotic area, cardiomyocyte size, and lung injury score were highest in group 4, lowest in groups 1 to 3 and significantly lower in group 6 than in group 5 (all P<0.0001). The protein expressions of fibrotic (Smad3/TGF-β), apoptotic (mitochondrial-Bax/cleaved-caspase3/PARP) and DNA-damaged (γ-H2AX) markers in lung and LV myocardium as well as oxidative (NOX-1/NOX2/oxidized protein) in LV myocardium exhibited an identical pattern of SL (all P<0.0001). The protein expressions of pressure/volume overload (BNP/MHC-β) mitochondrial-damaged (cytosolic cytochrome-C) of LV myocardium exhibited an identical pattern of SL (all P<0.001). In conclusion, Entresto is non-inferior to enalapril for protecting the heart-lung against CPS.
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ss31 therapy effectively protects the heart against transverse Aortic Constriction induced hypertrophic cardiomyopathy damage
2017Co-Authors: Fanyen Lee, Sarah Chua, Peihsun Sung, Jiunnjye Sheu, Christopher Glenn Wallace, Kuanhung Chen, Mengshen Tong, Tienhung Huang, Yiling Chen, Peilin ShaoAbstract:This study tested the hypothesis that SS31 therapy could effectively protect the heart against transverse Aortic Constriction (TAC)-induced hypertrophic cardiomyopathy (HCM) damage. Adult-male B6 mice (n=36) were equally divided into sham-operated control (group 1), TAC only (group 2) and TAC+SS31 (group) (2.0 mg/kg/day by intra-peritoneal administration from day 28 after TAC induction) and euthanized by day 60. In vitro results showed that SS31 markedly suppressed angiotensin-II induced protein expressions of BNP/β-MHC, ATM, p-P38 and P53 and ATP damage in H9C2 cells, and protein expression of pro-collagen-I/CTGF in fibroblasts (all P<0.001). By day 60, left ventricular ejection fraction (LVEF) and sarcomere length were significantly lower in group 2 than groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the LEVDd/LVESd and ratio of heart weight to tibial length showed an opposite pattern to LVEF (all P<0.0001). Microscopic findings of numbers of apoptotic nuclei, inflammatory (CD14+, F4/80+) and oxidative-stress (H2DCFDA+) biomarkers, disorganized score of endocardium, and fibrotic and collagen-deposition areas showed an opposite pattern to LVEF among the three groups (all P<0.0001). The protein expressions of inflammatory (PDGF/TNF-α/NF-κB/COX-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), fibrotic (TGF-β/Smad3) apoptotic (cleaved-caspase-3/cleaved-PARP), pressure/volume overload (BNP/β-MHC), CTGF, mitochondrial-damaged (cytosolic cytochrome-C), p-ERK1/2, p-Akt and PI3K signaling showed an opposite pattern to LVEF among the three groups (all P<0.001). The protein expression of anti-oxidants (HO-1/Nrf2) were significantly progressively increased in groups 1 to 3 (all P<0.001). In conclusion, SS31 therapy effectively protected the heart against TAC-induced damage.
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administration of antioxidant peptide ss 31 attenuates transverse Aortic Constriction induced pulmonary arterial hypertension in mice
2016Co-Authors: Tienhung Huang, Shengying Chung, Sarah Chua, Peihsun Sung, Yunglung Chen, Hanyan Chai, Chufeng Liu, Cheukkwan Sun, Hsuehwen Chang, Yenyi ZhenAbstract:Antioxidant peptide SS-31 is a class of cell-permeable small peptides, which selectively resides on the inner mitochondrial membrane and possesses intrinsic mitochondrial protective capacities. In this study we investigated the therapeutic effects of antioxidant peptide SS-31 on transverse Aortic Constriction (TAC)-induced pulmonary arterial hypertension (PAH) in a murine model. Adult male mice were divided into 3 groups: sham-operated mice, TAC mice, and TAC+SS-31 mice that underwent TAC surgery and received SS-31 (2 mg/d, ip) for 60 d. The right ventricular systolic blood pressure (RVSBP) was measured on d 60 prior to sacrificing the mice; then their right heart and lung tissues were collected for histological and biochemical examinations. Lung injury scores were defined by the increased crowded area and decreased number of alveolar sacs. TAC mice showed significantly higher RVSBP compared with sham-operated mice, the elevation was substantially suppressed in TAC+SS-31 mice. The same pattern of changes was found in pulmonary levels of oxidative stress proteins (NOX-1/NOX-2/oxidized proteins), cytosolic cytochrome c, biomarkers related to inflammation (MMP-9/TNF-α/iNOS), calcium overload index (TRPC1, 2, 4, 6), apoptosis (mitochondrial BAX, cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxic (HIF-1α), DNA damage (γ-H2AX) and endothelial function (eNOS/ET-1R), as well as in lung injury score, number of muscularized vessels in lungs, number of TRPC1+ and HIF-1α+ cells in pulmonary artery, and number of γ-H2AX+ and Ki-67+ cells in lung parenchyma. An opposite pattern of changes was observed in pulmonary anti-fibrotic markers (Smad1/5, BMP-2), number of small vessels, and number of alveolar sacs. In contrast, the levels of antioxidant proteins (HO-1/NQO-1/GR/GPx) in lung parenchyma were progressively and significantly increased from sham-operated mice, TAC mice to TAC+SS-31 mice. Antioxidant peptide SS-31 administration effectively attenuates TAC-induced PAH in mice.
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abstract 9851 benefit of antioxidant peptide ss 31 treatment in attenuating transverse Aortic Constriction induced pulmonary arterial hypertension in mice
2015Co-Authors: Shengying Chung, Sarah Chua, Tzuhsien Tsai, Peihsun Sung, Yunglung Chen, Steve Leu, Jiunnjye Sheu, Honkan YipAbstract:Introduction: We investigated the effect of mitochondria-targeted antioxidant peptide SS-31 on transthoracic Aortic Constriction (TAC)-induced pulmonary arterial hypertension (PAH) in mice. Methods...
Yunglung Chen - One of the best experts on this subject based on the ideXlab platform.
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administration of antioxidant peptide ss 31 attenuates transverse Aortic Constriction induced pulmonary arterial hypertension in mice
2016Co-Authors: Tienhung Huang, Shengying Chung, Sarah Chua, Peihsun Sung, Yunglung Chen, Hanyan Chai, Chufeng Liu, Cheukkwan Sun, Hsuehwen Chang, Yenyi ZhenAbstract:Antioxidant peptide SS-31 is a class of cell-permeable small peptides, which selectively resides on the inner mitochondrial membrane and possesses intrinsic mitochondrial protective capacities. In this study we investigated the therapeutic effects of antioxidant peptide SS-31 on transverse Aortic Constriction (TAC)-induced pulmonary arterial hypertension (PAH) in a murine model. Adult male mice were divided into 3 groups: sham-operated mice, TAC mice, and TAC+SS-31 mice that underwent TAC surgery and received SS-31 (2 mg/d, ip) for 60 d. The right ventricular systolic blood pressure (RVSBP) was measured on d 60 prior to sacrificing the mice; then their right heart and lung tissues were collected for histological and biochemical examinations. Lung injury scores were defined by the increased crowded area and decreased number of alveolar sacs. TAC mice showed significantly higher RVSBP compared with sham-operated mice, the elevation was substantially suppressed in TAC+SS-31 mice. The same pattern of changes was found in pulmonary levels of oxidative stress proteins (NOX-1/NOX-2/oxidized proteins), cytosolic cytochrome c, biomarkers related to inflammation (MMP-9/TNF-α/iNOS), calcium overload index (TRPC1, 2, 4, 6), apoptosis (mitochondrial BAX, cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxic (HIF-1α), DNA damage (γ-H2AX) and endothelial function (eNOS/ET-1R), as well as in lung injury score, number of muscularized vessels in lungs, number of TRPC1+ and HIF-1α+ cells in pulmonary artery, and number of γ-H2AX+ and Ki-67+ cells in lung parenchyma. An opposite pattern of changes was observed in pulmonary anti-fibrotic markers (Smad1/5, BMP-2), number of small vessels, and number of alveolar sacs. In contrast, the levels of antioxidant proteins (HO-1/NQO-1/GR/GPx) in lung parenchyma were progressively and significantly increased from sham-operated mice, TAC mice to TAC+SS-31 mice. Antioxidant peptide SS-31 administration effectively attenuates TAC-induced PAH in mice.
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exendin 4 therapy still offered an additional benefit on reducing transverse Aortic Constriction induced cardiac hypertrophy caused myocardial damage in dpp 4 deficient rats
2016Co-Authors: Shengying Chung, Sarah Chua, Yunglung Chen, Jiunnjye Sheu, Yiling Chen, Chufeng Liu, Yenyi Zhen, Teinhung Huang, Mengwei Chang, Honkan YipAbstract:Inhibition of dipeptidyl peptidase-IV (DPP-4) enzyme activity has been revealed to protect myocardium from ischemia-reperfusion through enhancing the endogenous glucagon-like peptide-1 (GLP-1) level. However, whether exogenous supply of exendin-4, an analogue of GLP-1, would still offer benefit for protecting myocardial damage from trans-Aortic Constriction (TAC)-induced hypertrophic cardiomyopathy in preexistence of DPP-4 deficiency (DPP-4(D)) remained unclear. Male-adult (DPP-4(D)) rats (n = 32) were randomized into group 1 [sham control (SC)], group 2 (DPP-4(D) + TAC), group 3 [DPP-4(D) + TAC + exendin-4 10 µg/day], and group 4 [DPP-4(D) + TAC + exendin-4 10 µg + exendin-9-39 10 µg/day]. The rats were sacrificed by day 60 after last echocardiographic examination. By day 60 after TAC, left ventricular ejection fraction (LVEF) (%) was highest in group 1 and lowest in group 2, and significantly lower in group 4 than that in group 3 (all p < 0.001). The protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), inflammatory (MMP-9, TNF-α, NF-κB), apoptotic (Bax, cleaved caspase 3 and PARP), fibrotic (TGF-β, Smad3), heart failure (BNP, β-MHC), DNA damaged (γ-H2AX) and ischemic stress (p-P38, p-Akt, p53, ATM) biomarkers showed an opposite pattern of LVEF among the four groups (all p < 0.03). Fibrotic area (by Masson's trichrome, Sirius red), and cellular expressions of DNA-damaged markers (Ki-67+, γ-H2AX+, CD90+/53BP1+) displayed an identical pattern, whereas cellular expressions of angiogenesis (CD31+, α-SMA+) and sarcomere length exhibited an opposite pattern compared to that of oxidative stress among the four groups (all p < 0.001). Take altogether, Exendin-4 effectively suppressed TAC-induced pathological cardiac hypertrophy in DPP-4(D) rat.
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abstract 9851 benefit of antioxidant peptide ss 31 treatment in attenuating transverse Aortic Constriction induced pulmonary arterial hypertension in mice
2015Co-Authors: Shengying Chung, Sarah Chua, Tzuhsien Tsai, Peihsun Sung, Yunglung Chen, Steve Leu, Jiunnjye Sheu, Honkan YipAbstract:Introduction: We investigated the effect of mitochondria-targeted antioxidant peptide SS-31 on transthoracic Aortic Constriction (TAC)-induced pulmonary arterial hypertension (PAH) in mice. Methods...