Extracorporeal shock wave treatment attenuated left ventricular dysfunction and remodeling in mini-pig with cardiorenal syndrome

Jiunn Jye Sheu; Hani E.E. Ali; Ben Chung Cheng; Hsin Ju Chiang; Pei Hsun Sung; Kuan Hung Chen; Chih Chao Yang; Yen Ta Chen; John Y. Chiang; Pao Yuan Lin; Sarah Chua; Han Tan Chai; Sheng Ying Chung; Cheuk Kwan Sun; Hon Kan Yip

doi:10.18632/oncotarget.18287

Extracorporeal shock wave treatment attenuated left ventricular dysfunction and remodeling in mini-pig with cardiorenal syndrome

Jiunn Jye Sheu
, Hani E.E. Ali
, Ben Chung Cheng
, Hsin Ju Chiang
, Pei Hsun Sung
, Kuan Hung Chen
, Chih Chao Yang
, Yen Ta Chen
, John Y. Chiang
, Pao Yuan Lin
, Sarah Chua
, Han Tan Chai
, Sheng Ying Chung
, Cheuk Kwan Sun
, Hon Kan Yip^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Journal Article › peer-review

13 Scopus citations

Abstract

This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomlydivided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0.1 mJ/m²/equally to 4-ischemic regions by day-90 after LAD constriction], and group 5 (LV-ischemia-CKD + ECSW). By day-180 after CKD induction, echocardiography showed that LV ejection fraction (LVEF) was highest in group 1, lowest in group 3, significantly lower in group 2 than that in groups 4 and 5, and significantly lower in group 5 than that in group 4, whereas LV-end systolic and diastolic dimensions displayed an opposite pattern (all p < 0.001). Protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax), fibrotic (TGF-β/Smad3), pressure/volume-overload (BNP/β-MHC), endothelial (CD31/vWF) and mitochondrial-integrity (PGC-1/mitochondrial-cytochrome-C) biomarkers exhibited a pattern identical to that of LVEF, whereas angiogenesis factors (VEGF/CXCR4/SDF-1α) showed significant progressive increase among all groups (all p < 0.0001). Microscopic findings of CD31+cells/vWF+cells/small-vessel density/sarcomerelength showed an identical pattern, whereas collagen-deposition area/fibrotic area/apoptotic nuclei expressed an opposite pattern compared to that of LVEF among all groups (all p < 0.0001). In conclusion, CKD aggravated ischemia-induced LV dysfunction and remodeling and molecular-cellular perturbations that were reversed by ECSW treatment.

Original language	English
Pages (from-to)	54747-54763
Number of pages	17
Journal	Oncotarget
Volume	8
Issue number	33
DOIs	https://doi.org/10.18632/oncotarget.18287
State	Published - 2017

Bibliographical note

Publisher Copyright:
© Sheu et al.

Keywords

Angiogenesis
Cardiorenal syndrome
Extracorporeal shock wave
LV remodeling
Myocardial ischemia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.18287

Cite this

Sheu, J. J., Ali, H. E. E., Cheng, B. C., Chiang, H. J., Sung, P. H., Chen, K. H., Yang, C. C., Chen, Y. T., Chiang, J. Y., Lin, P. Y., Chua, S., Chai, H. T., Chung, S. Y., Sun, C. K., & Yip, H. K. (2017). Extracorporeal shock wave treatment attenuated left ventricular dysfunction and remodeling in mini-pig with cardiorenal syndrome. Oncotarget, 8(33), 54747-54763. https://doi.org/10.18632/oncotarget.18287

@article{1d05306765d549ccb50be1efae29be25,

title = "Extracorporeal shock wave treatment attenuated left ventricular dysfunction and remodeling in mini-pig with cardiorenal syndrome",

abstract = "This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomlydivided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0.1 mJ/m2/equally to 4-ischemic regions by day-90 after LAD constriction], and group 5 (LV-ischemia-CKD + ECSW). By day-180 after CKD induction, echocardiography showed that LV ejection fraction (LVEF) was highest in group 1, lowest in group 3, significantly lower in group 2 than that in groups 4 and 5, and significantly lower in group 5 than that in group 4, whereas LV-end systolic and diastolic dimensions displayed an opposite pattern (all p < 0.001). Protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax), fibrotic (TGF-β/Smad3), pressure/volume-overload (BNP/β-MHC), endothelial (CD31/vWF) and mitochondrial-integrity (PGC-1/mitochondrial-cytochrome-C) biomarkers exhibited a pattern identical to that of LVEF, whereas angiogenesis factors (VEGF/CXCR4/SDF-1α) showed significant progressive increase among all groups (all p < 0.0001). Microscopic findings of CD31+cells/vWF+cells/small-vessel density/sarcomerelength showed an identical pattern, whereas collagen-deposition area/fibrotic area/apoptotic nuclei expressed an opposite pattern compared to that of LVEF among all groups (all p < 0.0001). In conclusion, CKD aggravated ischemia-induced LV dysfunction and remodeling and molecular-cellular perturbations that were reversed by ECSW treatment.",

keywords = "Angiogenesis, Cardiorenal syndrome, Extracorporeal shock wave, LV remodeling, Myocardial ischemia",

author = "Sheu, \{Jiunn Jye\} and Ali, \{Hani E.E.\} and Cheng, \{Ben Chung\} and Chiang, \{Hsin Ju\} and Sung, \{Pei Hsun\} and Chen, \{Kuan Hung\} and Yang, \{Chih Chao\} and Chen, \{Yen Ta\} and Chiang, \{John Y.\} and Lin, \{Pao Yuan\} and Sarah Chua and Chai, \{Han Tan\} and Chung, \{Sheng Ying\} and Sun, \{Cheuk Kwan\} and Yip, \{Hon Kan\}",

note = "Publisher Copyright: {\textcopyright} Sheu et al.",

year = "2017",

doi = "10.18632/oncotarget.18287",

language = "英语",

volume = "8",

pages = "54747--54763",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals LLC",

number = "33",

}

Sheu, JJ, Ali, HEE, Cheng, BC, Chiang, HJ, Sung, PH, Chen, KH, Yang, CC, Chen, YT, Chiang, JY, Lin, PY, Chua, S, Chai, HT, Chung, SY, Sun, CK & Yip, HK 2017, 'Extracorporeal shock wave treatment attenuated left ventricular dysfunction and remodeling in mini-pig with cardiorenal syndrome', Oncotarget, vol. 8, no. 33, pp. 54747-54763. https://doi.org/10.18632/oncotarget.18287

TY - JOUR

T1 - Extracorporeal shock wave treatment attenuated left ventricular dysfunction and remodeling in mini-pig with cardiorenal syndrome

AU - Sheu, Jiunn Jye

AU - Ali, Hani E.E.

AU - Cheng, Ben Chung

AU - Chiang, Hsin Ju

AU - Sung, Pei Hsun

AU - Chen, Kuan Hung

AU - Yang, Chih Chao

AU - Chen, Yen Ta

AU - Chiang, John Y.

AU - Lin, Pao Yuan

AU - Chua, Sarah

AU - Chai, Han Tan

AU - Chung, Sheng Ying

AU - Sun, Cheuk Kwan

AU - Yip, Hon Kan

PY - 2017

Y1 - 2017

N2 - This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomlydivided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0.1 mJ/m2/equally to 4-ischemic regions by day-90 after LAD constriction], and group 5 (LV-ischemia-CKD + ECSW). By day-180 after CKD induction, echocardiography showed that LV ejection fraction (LVEF) was highest in group 1, lowest in group 3, significantly lower in group 2 than that in groups 4 and 5, and significantly lower in group 5 than that in group 4, whereas LV-end systolic and diastolic dimensions displayed an opposite pattern (all p < 0.001). Protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax), fibrotic (TGF-β/Smad3), pressure/volume-overload (BNP/β-MHC), endothelial (CD31/vWF) and mitochondrial-integrity (PGC-1/mitochondrial-cytochrome-C) biomarkers exhibited a pattern identical to that of LVEF, whereas angiogenesis factors (VEGF/CXCR4/SDF-1α) showed significant progressive increase among all groups (all p < 0.0001). Microscopic findings of CD31+cells/vWF+cells/small-vessel density/sarcomerelength showed an identical pattern, whereas collagen-deposition area/fibrotic area/apoptotic nuclei expressed an opposite pattern compared to that of LVEF among all groups (all p < 0.0001). In conclusion, CKD aggravated ischemia-induced LV dysfunction and remodeling and molecular-cellular perturbations that were reversed by ECSW treatment.

AB - This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomlydivided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0.1 mJ/m2/equally to 4-ischemic regions by day-90 after LAD constriction], and group 5 (LV-ischemia-CKD + ECSW). By day-180 after CKD induction, echocardiography showed that LV ejection fraction (LVEF) was highest in group 1, lowest in group 3, significantly lower in group 2 than that in groups 4 and 5, and significantly lower in group 5 than that in group 4, whereas LV-end systolic and diastolic dimensions displayed an opposite pattern (all p < 0.001). Protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax), fibrotic (TGF-β/Smad3), pressure/volume-overload (BNP/β-MHC), endothelial (CD31/vWF) and mitochondrial-integrity (PGC-1/mitochondrial-cytochrome-C) biomarkers exhibited a pattern identical to that of LVEF, whereas angiogenesis factors (VEGF/CXCR4/SDF-1α) showed significant progressive increase among all groups (all p < 0.0001). Microscopic findings of CD31+cells/vWF+cells/small-vessel density/sarcomerelength showed an identical pattern, whereas collagen-deposition area/fibrotic area/apoptotic nuclei expressed an opposite pattern compared to that of LVEF among all groups (all p < 0.0001). In conclusion, CKD aggravated ischemia-induced LV dysfunction and remodeling and molecular-cellular perturbations that were reversed by ECSW treatment.

KW - Angiogenesis

KW - Cardiorenal syndrome

KW - Extracorporeal shock wave

KW - LV remodeling

KW - Myocardial ischemia

UR - https://www.scopus.com/pages/publications/85029124118

U2 - 10.18632/oncotarget.18287

DO - 10.18632/oncotarget.18287

M3 - 文章

C2 - 28903379

AN - SCOPUS:85029124118

SN - 1949-2553

VL - 8

SP - 54747

EP - 54763

JO - Oncotarget

JF - Oncotarget

IS - 33

ER -

Extracorporeal shock wave treatment attenuated left ventricular dysfunction and remodeling in mini-pig with cardiorenal syndrome

Abstract

Bibliographical note

Keywords

UN SDGs

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