Abstract
Inflammation is a common cause of cardiac arrhythmia. Angiotensin II (Ang II) is a major contributing factor in the pathogenesis of cardiac inflammation; however, its underlying molecular mechanism remains unclear. Here, we explored the effect of Ang II on inflammatory mechanisms and oxidative stress using HL-1 atrial myocytes. We showed that Ang II activated c-Jun N-terminal kinase (JNK) phosphorylation and other inflammatory markers, such as transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Ang II decreased oxygen consumption rate, which resulted in reactive oxygen species (ROS) generation and inhibition of ROS blocked Ang II-mediated JNK phosphorylation and TGF-β1 induction. Ang II induced the expression of its specific receptor, AT1R. Ang II-induced intracellular calcium production associated with Ang II-mediated signalling pathways. In addition, the generated ROS and calcium stimulated AMPK phosphorylation. Inhibiting AMPK blocked Ang II-mediated JNK and TGF-β signalling pathways. Ang II concentration, along with TGF-β1 and tumor necrosis factor-α levels, was slightly increased in plasma of patients with atrial fibrillation. Taken together, these results suggest that Ang II induces inflammation mechanisms through an AMPK-related signalling pathway. Our results provide new molecular targets for the development of therapeutics for inflammation-related conditions, such as atrial fibrillation.
| Original language | English |
|---|---|
| Article number | 10328 |
| Journal | Scientific Reports |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2017 Dec 1 |
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Angiotensin II affects inflammation mechanisms via AMPK-related signalling pathways in HL-1 atrial myocytes. / Kim, Nami; Jung, Youngae; Nam, Miso; Sun Kang, Mi; Lee, Min Kyung; Cho, Youngjin; Choi, Eue Keun; Hwang, Geum Sook; Kim, Hyeon Soo.
In: Scientific Reports, Vol. 7, No. 1, 10328, 01.12.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Angiotensin II affects inflammation mechanisms via AMPK-related signalling pathways in HL-1 atrial myocytes
AU - Kim, Nami
AU - Jung, Youngae
AU - Nam, Miso
AU - Sun Kang, Mi
AU - Lee, Min Kyung
AU - Cho, Youngjin
AU - Choi, Eue Keun
AU - Hwang, Geum Sook
AU - Kim, Hyeon Soo
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Inflammation is a common cause of cardiac arrhythmia. Angiotensin II (Ang II) is a major contributing factor in the pathogenesis of cardiac inflammation; however, its underlying molecular mechanism remains unclear. Here, we explored the effect of Ang II on inflammatory mechanisms and oxidative stress using HL-1 atrial myocytes. We showed that Ang II activated c-Jun N-terminal kinase (JNK) phosphorylation and other inflammatory markers, such as transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Ang II decreased oxygen consumption rate, which resulted in reactive oxygen species (ROS) generation and inhibition of ROS blocked Ang II-mediated JNK phosphorylation and TGF-β1 induction. Ang II induced the expression of its specific receptor, AT1R. Ang II-induced intracellular calcium production associated with Ang II-mediated signalling pathways. In addition, the generated ROS and calcium stimulated AMPK phosphorylation. Inhibiting AMPK blocked Ang II-mediated JNK and TGF-β signalling pathways. Ang II concentration, along with TGF-β1 and tumor necrosis factor-α levels, was slightly increased in plasma of patients with atrial fibrillation. Taken together, these results suggest that Ang II induces inflammation mechanisms through an AMPK-related signalling pathway. Our results provide new molecular targets for the development of therapeutics for inflammation-related conditions, such as atrial fibrillation.
AB - Inflammation is a common cause of cardiac arrhythmia. Angiotensin II (Ang II) is a major contributing factor in the pathogenesis of cardiac inflammation; however, its underlying molecular mechanism remains unclear. Here, we explored the effect of Ang II on inflammatory mechanisms and oxidative stress using HL-1 atrial myocytes. We showed that Ang II activated c-Jun N-terminal kinase (JNK) phosphorylation and other inflammatory markers, such as transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Ang II decreased oxygen consumption rate, which resulted in reactive oxygen species (ROS) generation and inhibition of ROS blocked Ang II-mediated JNK phosphorylation and TGF-β1 induction. Ang II induced the expression of its specific receptor, AT1R. Ang II-induced intracellular calcium production associated with Ang II-mediated signalling pathways. In addition, the generated ROS and calcium stimulated AMPK phosphorylation. Inhibiting AMPK blocked Ang II-mediated JNK and TGF-β signalling pathways. Ang II concentration, along with TGF-β1 and tumor necrosis factor-α levels, was slightly increased in plasma of patients with atrial fibrillation. Taken together, these results suggest that Ang II induces inflammation mechanisms through an AMPK-related signalling pathway. Our results provide new molecular targets for the development of therapeutics for inflammation-related conditions, such as atrial fibrillation.
UR - http://www.scopus.com/inward/record.url?scp=85028816615&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028816615&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-09675-3
DO - 10.1038/s41598-017-09675-3
M3 - Article
C2 - 28871102
AN - SCOPUS:85028816615
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 10328
ER -