Advanced oxidation protein products aggravate cardiac remodeling via cardiomyocyte apoptosis in chronic kidney disease

Weijing Feng, Kun Zhang, Yu Liu, Jie Chen, Qingqing Cai, Wanbing He, Yinyin Zhang, Mong-Heng Wang, Jingfeng Wang, Hui Huang

Research output: Contribution to journalArticle

  • 1 Citations

Abstract

Advanced oxidation protein products (AOPPs) are independent risk factor for various cardiovascular diseases. Cardiomyocyte apoptosis has been implicated as an important mechanism in cardiac remodeling in chronic kidney disease (CKD). However, whether AOPPs affect cardiomyocyte apoptosis and subsequent cardiac remodeling in CKD is still not very clear. Here, we assessed the role of AOPPs in cardiomyocyte apoptosis in CKD. H9C2 rat cardiomyoblast cells were exposed to AOPPs. Apoptotic cells were determined by TUNEL assay. The expression of apoptotic markers (cleaved caspase-3 and Bax), JNK signaling, and endoplasmic reticulum stress were explored. Serum AOPPs were measured in male Sprague-Dawley rats that underwent sham surgery and 5/6 nephrectomy, respectively. In vitro, our findings showed that AOPPs activated JNK signaling and endoplasmic reticulum stress and significantly aggravated H9C2 rat cardiomyoblast cells apoptosis. These effects were partially ameliorated by apocynin with inhibition of oxidative stress. In vivo, serum levels of AOPPs were progressively elevated with the increasing time course in CKD rats compared with sham-operated rats (P < 0.05). Serum AOPP levels were positively associated with cardiomyocyte apoptosis (R2 = 0.76, P < 0.01). In conclusion, AOPPs aggravate cardiomyocyte apoptosis in vitro, and these effects are partially prevented by apocynin via suppressing JNK signaling and endoplasmic reticulum stress with oxidative stress inhibition. In vivo, AOPPs are increased in the CKD model and may contribute to the cardiac pathogenesis, but at this point it is unclear if that is true. These results suggest that pharmacological approaches to attenuate AOPP-aggravated cardiomyocyte apoptosis may be beneficial to improve cardiac remodeling in CKD. NEW & NOTEWORTHY Here, we present new evidence to show that advanced oxidation protein products aggravate cardiomyocyte apoptosis and subsequent cardiac remodeling via upregulations of JNK signaling and endoplasmic reticulum stress in chronic kidney disease. Such processes are mainly prevented by apocynin via oxidative stress inhibition.

LanguageEnglish (US)
PagesH475-H483
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume314
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Advanced Oxidation Protein Products
Chronic Renal Insufficiency
Cardiac Myocytes
Apoptosis
Endoplasmic Reticulum Stress
Oxidative Stress
Serum
In Situ Nick-End Labeling
Nephrectomy
Caspase 3

Keywords

  • Advanced oxidation protein products
  • Cardiac remodeling
  • Cardiomyocyte apoptosis
  • Chronic kidney disease

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Advanced oxidation protein products aggravate cardiac remodeling via cardiomyocyte apoptosis in chronic kidney disease. / Feng, Weijing; Zhang, Kun; Liu, Yu; Chen, Jie; Cai, Qingqing; He, Wanbing; Zhang, Yinyin; Wang, Mong-Heng; Wang, Jingfeng; Huang, Hui.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 314, No. 3, 01.03.2018, p. H475-H483.

Research output: Contribution to journalArticle

Feng, Weijing ; Zhang, Kun ; Liu, Yu ; Chen, Jie ; Cai, Qingqing ; He, Wanbing ; Zhang, Yinyin ; Wang, Mong-Heng ; Wang, Jingfeng ; Huang, Hui. / Advanced oxidation protein products aggravate cardiac remodeling via cardiomyocyte apoptosis in chronic kidney disease. In: American Journal of Physiology - Heart and Circulatory Physiology. 2018 ; Vol. 314, No. 3. pp. H475-H483.
@article{26f4c3c99dcb414e89b5c9878b04561a,
title = "Advanced oxidation protein products aggravate cardiac remodeling via cardiomyocyte apoptosis in chronic kidney disease",
abstract = "Advanced oxidation protein products (AOPPs) are independent risk factor for various cardiovascular diseases. Cardiomyocyte apoptosis has been implicated as an important mechanism in cardiac remodeling in chronic kidney disease (CKD). However, whether AOPPs affect cardiomyocyte apoptosis and subsequent cardiac remodeling in CKD is still not very clear. Here, we assessed the role of AOPPs in cardiomyocyte apoptosis in CKD. H9C2 rat cardiomyoblast cells were exposed to AOPPs. Apoptotic cells were determined by TUNEL assay. The expression of apoptotic markers (cleaved caspase-3 and Bax), JNK signaling, and endoplasmic reticulum stress were explored. Serum AOPPs were measured in male Sprague-Dawley rats that underwent sham surgery and 5/6 nephrectomy, respectively. In vitro, our findings showed that AOPPs activated JNK signaling and endoplasmic reticulum stress and significantly aggravated H9C2 rat cardiomyoblast cells apoptosis. These effects were partially ameliorated by apocynin with inhibition of oxidative stress. In vivo, serum levels of AOPPs were progressively elevated with the increasing time course in CKD rats compared with sham-operated rats (P < 0.05). Serum AOPP levels were positively associated with cardiomyocyte apoptosis (R2 = 0.76, P < 0.01). In conclusion, AOPPs aggravate cardiomyocyte apoptosis in vitro, and these effects are partially prevented by apocynin via suppressing JNK signaling and endoplasmic reticulum stress with oxidative stress inhibition. In vivo, AOPPs are increased in the CKD model and may contribute to the cardiac pathogenesis, but at this point it is unclear if that is true. These results suggest that pharmacological approaches to attenuate AOPP-aggravated cardiomyocyte apoptosis may be beneficial to improve cardiac remodeling in CKD. NEW & NOTEWORTHY Here, we present new evidence to show that advanced oxidation protein products aggravate cardiomyocyte apoptosis and subsequent cardiac remodeling via upregulations of JNK signaling and endoplasmic reticulum stress in chronic kidney disease. Such processes are mainly prevented by apocynin via oxidative stress inhibition.",
keywords = "Advanced oxidation protein products, Cardiac remodeling, Cardiomyocyte apoptosis, Chronic kidney disease",
author = "Weijing Feng and Kun Zhang and Yu Liu and Jie Chen and Qingqing Cai and Wanbing He and Yinyin Zhang and Mong-Heng Wang and Jingfeng Wang and Hui Huang",
year = "2018",
month = "3",
day = "1",
doi = "10.1152/ajpheart.00628.2016",
language = "English (US)",
volume = "314",
pages = "H475--H483",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Advanced oxidation protein products aggravate cardiac remodeling via cardiomyocyte apoptosis in chronic kidney disease

AU - Feng, Weijing

AU - Zhang, Kun

AU - Liu, Yu

AU - Chen, Jie

AU - Cai, Qingqing

AU - He, Wanbing

AU - Zhang, Yinyin

AU - Wang, Mong-Heng

AU - Wang, Jingfeng

AU - Huang, Hui

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Advanced oxidation protein products (AOPPs) are independent risk factor for various cardiovascular diseases. Cardiomyocyte apoptosis has been implicated as an important mechanism in cardiac remodeling in chronic kidney disease (CKD). However, whether AOPPs affect cardiomyocyte apoptosis and subsequent cardiac remodeling in CKD is still not very clear. Here, we assessed the role of AOPPs in cardiomyocyte apoptosis in CKD. H9C2 rat cardiomyoblast cells were exposed to AOPPs. Apoptotic cells were determined by TUNEL assay. The expression of apoptotic markers (cleaved caspase-3 and Bax), JNK signaling, and endoplasmic reticulum stress were explored. Serum AOPPs were measured in male Sprague-Dawley rats that underwent sham surgery and 5/6 nephrectomy, respectively. In vitro, our findings showed that AOPPs activated JNK signaling and endoplasmic reticulum stress and significantly aggravated H9C2 rat cardiomyoblast cells apoptosis. These effects were partially ameliorated by apocynin with inhibition of oxidative stress. In vivo, serum levels of AOPPs were progressively elevated with the increasing time course in CKD rats compared with sham-operated rats (P < 0.05). Serum AOPP levels were positively associated with cardiomyocyte apoptosis (R2 = 0.76, P < 0.01). In conclusion, AOPPs aggravate cardiomyocyte apoptosis in vitro, and these effects are partially prevented by apocynin via suppressing JNK signaling and endoplasmic reticulum stress with oxidative stress inhibition. In vivo, AOPPs are increased in the CKD model and may contribute to the cardiac pathogenesis, but at this point it is unclear if that is true. These results suggest that pharmacological approaches to attenuate AOPP-aggravated cardiomyocyte apoptosis may be beneficial to improve cardiac remodeling in CKD. NEW & NOTEWORTHY Here, we present new evidence to show that advanced oxidation protein products aggravate cardiomyocyte apoptosis and subsequent cardiac remodeling via upregulations of JNK signaling and endoplasmic reticulum stress in chronic kidney disease. Such processes are mainly prevented by apocynin via oxidative stress inhibition.

AB - Advanced oxidation protein products (AOPPs) are independent risk factor for various cardiovascular diseases. Cardiomyocyte apoptosis has been implicated as an important mechanism in cardiac remodeling in chronic kidney disease (CKD). However, whether AOPPs affect cardiomyocyte apoptosis and subsequent cardiac remodeling in CKD is still not very clear. Here, we assessed the role of AOPPs in cardiomyocyte apoptosis in CKD. H9C2 rat cardiomyoblast cells were exposed to AOPPs. Apoptotic cells were determined by TUNEL assay. The expression of apoptotic markers (cleaved caspase-3 and Bax), JNK signaling, and endoplasmic reticulum stress were explored. Serum AOPPs were measured in male Sprague-Dawley rats that underwent sham surgery and 5/6 nephrectomy, respectively. In vitro, our findings showed that AOPPs activated JNK signaling and endoplasmic reticulum stress and significantly aggravated H9C2 rat cardiomyoblast cells apoptosis. These effects were partially ameliorated by apocynin with inhibition of oxidative stress. In vivo, serum levels of AOPPs were progressively elevated with the increasing time course in CKD rats compared with sham-operated rats (P < 0.05). Serum AOPP levels were positively associated with cardiomyocyte apoptosis (R2 = 0.76, P < 0.01). In conclusion, AOPPs aggravate cardiomyocyte apoptosis in vitro, and these effects are partially prevented by apocynin via suppressing JNK signaling and endoplasmic reticulum stress with oxidative stress inhibition. In vivo, AOPPs are increased in the CKD model and may contribute to the cardiac pathogenesis, but at this point it is unclear if that is true. These results suggest that pharmacological approaches to attenuate AOPP-aggravated cardiomyocyte apoptosis may be beneficial to improve cardiac remodeling in CKD. NEW & NOTEWORTHY Here, we present new evidence to show that advanced oxidation protein products aggravate cardiomyocyte apoptosis and subsequent cardiac remodeling via upregulations of JNK signaling and endoplasmic reticulum stress in chronic kidney disease. Such processes are mainly prevented by apocynin via oxidative stress inhibition.

KW - Advanced oxidation protein products

KW - Cardiac remodeling

KW - Cardiomyocyte apoptosis

KW - Chronic kidney disease

UR - http://www.scopus.com/inward/record.url?scp=85043774005&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043774005&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00628.2016

DO - 10.1152/ajpheart.00628.2016

M3 - Article

VL - 314

SP - H475-H483

JO - American Journal of Physiology - Heart and Circulatory Physiology

T2 - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 3

ER -