Abstract: PUB418
Renal ACE 2, Inflammation, and Oxidative Stress Cross-Talk in Diet-Induced, Salt-Sensitive Hypertension in Mice with Obesity
Session Information
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Cai, Jiahui, Yanshan University, Qinhuangdao, Hebei, China
- Sun, Feifei, Yanshan University, Qinhuangdao, Hebei, China
- Zhao, Shasha, Yanshan University, Qinhuangdao, Hebei, China
- Sun, Yunbo, Yanshan University, Qinhuangdao, Hebei, China
- Pan, Qiaoyun, Yanshan University, Qinhuangdao, Hebei, China
- Yang, Feng, Yanshan University, Qinhuangdao, Hebei, China
- Tan, Runyan, Yanshan University, Qinhuangdao, Hebei, China
- Wang, Danshu, Yanshan University, Qinhuangdao, Hebei, China
- Pierre, Sandrine V., Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, West Virginia, United States
- Yan, Yanling, Yanshan University, Qinhuangdao, Hebei, China
Background
Obesity-induced salt-sensitive hypertension (ssHTN) is associated with inflammation and oxidative stress. Angiotensin Converting Enzyme type 2 (ACE2) is crucial in regulating blood pressure. This study aims to identify how renal ACE2, inflammation, and oxidative stress orchestrate to modulate blood pressure.
Methods
High-fat (HF)- induced obese C57BL/6J (B6) male mice were established as a model of ssHTN. Western blot was performed to monitor the effects of oxidative stress, inflammation, and Na/K-ATPase signaling pathway activation on ACE2 expression in the kidney. The related mechanisms affecting ACE2 expression were further verified in vitro.
Results
In the kidney of B6 mice, high salt (HS) stimulated signal transducer and activator of transcription 3 (Stat3), Extracellular Signal-Regulated Kinase 1/2 (Erk1/2) phosphorylation levels, and ACE2 expression. In our model of ssHTN caused by obesity, HF up-regulated phosphorylation of Stat3 and Erk1/2, as well as Heme Oxygenase-1 (HO-1) expression, but downregulated ACE2 expression compared with normal diet mice. These findings suggested that obese-mediated ssHTN was accompanied by inflammation and oxidative stress. The short-term activation of p-Stat3 and p-Erk1/2 by HS triggered a "defense response," contributing to significant upregulation of ACE2, which has the endogenous function of negative regulation of the renin-angiotensin system (RAS). However, persistent signaling activation caused by HF would disrupt the "defense response," leading to a dysfunctional ACE2 expression, which might ultimately contribute to the development of ssHTN. In vitro studies evidenced that Co(III) Protoporphyrin IX chloride (CoPP)-induced HO-1 attenuated IL-6-mediated p-Stat3 and p-Erk1/2 in porcine proximal tubular LLC-PK1 cells, suggesting the role of HO-1 in modulating the balance of "defense response.”
Conclusion
Our studies reveal a novel association between ACE2 expression in the kidney and the activation of p-Erk1/2 and p-Stat3, which not only provides a theoretical basis for the role of ACE2 targets in ssHTN but also offers promising avenues for its clinical treatment.
Funding
- NIDDK Support