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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | H475-H483 |
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 314 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2018 |
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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, 03.2018, p. H475-H483.Research output: Contribution to journal › Article
}
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
Y1 - 2018/3
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
C2 - 29101185
AN - SCOPUS:85043774005
VL - 314
SP - H475-H483
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 3
ER -