Enyong Su1,2, Linwei Zhao1,2, Xiaohang Yang1, Binbin Zhu1,2, Yahui Liu2, Wen Zhao3, Xianpei Wang1,2, Datun Qi1,2, Lijie Zhu1,2, Chuanyu Gao4,5. 1. Department of Cardiology, Zhengzhou University People's Hospital, No.7 Weiwu road, Jinshui District, Zhengzhou, 450003, Henan, China. 2. Department of Cardiology, Huazhong Fuwai Hospital, Zhengzhou, 451464, Henan, China. 3. Zhengzhou University School of Pharmaceutical Sciences, Zhengzhou, 450001, Henan, China. 4. Department of Cardiology, Zhengzhou University People's Hospital, No.7 Weiwu road, Jinshui District, Zhengzhou, 450003, Henan, China. gaocy6208@126.com. 5. Department of Cardiology, Huazhong Fuwai Hospital, Zhengzhou, 451464, Henan, China. gaocy6208@126.com.
Abstract
BACKGROUND: Renal denervation (RDN) targeting the sympathetic nerves in the renal arterial adventitia as a treatment of resistant hypertension can cause endothelial injury and vascular wall injury. This study aims to evaluate the risk of atherosclerosis induced by RDN in renal arteries. METHODS: A total of 15 minipigs were randomly assigned to 3 groups: (1) control group, (2) sham group, and (3) RDN group (n = 5 per group). All pigs were fed a high-fat diet (HFD) for 6 months after appropriate treatment. The degree of intimal thickening of renal artery and the conversion of endothelin 1 (ET-1) receptors were evaluated by histological staining. Western blot was used to assess the expression of nitric oxide (NO) synthesis signaling pathway, ET-1 and its receptors, NADPH oxidase 2 (NOX2) and 4-hydroxynonenal (4-HNE) proteins, and the activation of NF-kappa B (NF-κB). RESULTS: The histological staining results suggested that compared to the sham treatment, RDN led to significant intimal thickening and significantly promoted the production of endothelin B receptor (ETBR) in vascular smooth muscle cells (VSMCs). Western blotting analysis indicated that RDN significantly suppressed the expression of AMPK/Akt/eNOS signaling pathway proteins, and decreased the production of NO, and increased the expression of endothelin system proteins including endothelin-1 (ET-1), endothelin converting enzyme 1 (ECE1), endothelin A receptor (ETAR) and ETBR; and upregulated the expression of NOX2 and 4-HNE proteins and enhanced the activation of NF-kappa B (NF-κB) when compared with the sham treatment (all p < 0.05). There were no significant differences between the control and sham groups (all p > 0.05). CONCLUSIONS: RDN aggravated endothelial endocrine dysfunction and intimal thickening, and increased the risk of atherosclerosis in renal arteries of HFD-fed pigs.
BACKGROUND: Renal denervation (RDN) targeting the sympathetic nerves in the renal arterial adventitia as a treatment of resistant hypertension can cause endothelial injury and vascular wall injury. This study aims to evaluate the risk of atherosclerosis induced by RDN in renal arteries. METHODS: A total of 15 minipigs were randomly assigned to 3 groups: (1) control group, (2) sham group, and (3) RDN group (n = 5 per group). All pigs were fed a high-fat diet (HFD) for 6 months after appropriate treatment. The degree of intimal thickening of renal artery and the conversion of endothelin 1 (ET-1) receptors were evaluated by histological staining. Western blot was used to assess the expression of nitric oxide (NO) synthesis signaling pathway, ET-1 and its receptors, NADPH oxidase 2 (NOX2) and 4-hydroxynonenal (4-HNE) proteins, and the activation of NF-kappa B (NF-κB). RESULTS: The histological staining results suggested that compared to the sham treatment, RDN led to significant intimal thickening and significantly promoted the production of endothelin B receptor (ETBR) in vascular smooth muscle cells (VSMCs). Western blotting analysis indicated that RDN significantly suppressed the expression of AMPK/Akt/eNOS signaling pathway proteins, and decreased the production of NO, and increased the expression of endothelin system proteins including endothelin-1 (ET-1), endothelin converting enzyme 1 (ECE1), endothelin A receptor (ETAR) and ETBR; and upregulated the expression of NOX2 and 4-HNE proteins and enhanced the activation of NF-kappa B (NF-κB) when compared with the sham treatment (all p < 0.05). There were no significant differences between the control and sham groups (all p > 0.05). CONCLUSIONS: RDN aggravated endothelial endocrine dysfunction and intimal thickening, and increased the risk of atherosclerosis in renal arteries of HFD-fed pigs.
Authors: Amal F Dawood; Amro Maarouf; Norah M Alzamil; Maha A Momenah; Ayed A Shati; Nervana M Bayoumy; Samaa S Kamar; Mohamed A Haidara; Asmaa M ShamsEldeen; Hanaa Z Yassin; Peter W Hewett; Bahjat Al-Ani Journal: Biomedicines Date: 2022-07-08