微气泡
血压
医学
嘌呤能受体
基因传递
转染
内科学
受体
流式细胞术
颈动脉体
内分泌学
男科
免疫学
基因
化学
超声波
颈动脉
生物化学
放射科
作者
Qian Xue,Ruiyu Wang,Liang Wang,Bo Xiong,Lingjiao Li,Jun Qian,Lan Hao,Zhigang Wang,Dichuan Liu,Changming Deng,Shunkang Rong,Yuanqing Yao,Yonghong Jiang,Que Zhu,Jing Huang
标识
DOI:10.1016/j.trsl.2020.06.005
摘要
The purinergic P2X3 receptor in the carotid body (CB) is considered a new target for treating hypertension, although approaches for targeted regulating P2X3 receptor expression are lacking. Here, we explored the feasibility of targeted P2X3 receptor down-regulation in CBs by localized low-intensity focused ultrasound (LIFU)-mediated gene delivery to reduce the blood pressure. Thirty-two Kunming canines were randomly assigned to the treatment group (n = 14), negative control group (n = 10), LIFU + cationic microbubbles group (n = 4), and LIFU-only group (n = 4). Plasmid-loaded cationic microbubbles were injected and bilateral CBs were irradiated with a LIFU-based transducer. Flow cytometry showed that 33.15% of transfected cells expressed the green fluorescent protein reporter gene. T7 endonuclease I assays showed an insertion-deletion rate of 8.30%. The P2X3 receptor mRNA- and protein-expression levels in CBs decreased by 56.31% and 45.10%, respectively, in the treatment group. Mean systolic (152.5 ± 3.0 vs 138.0 ± 2.9 mm Hg, P = 0.003) and diastolic (97.8 ± 1.5 vs 87.2 ± 2.3 mm Hg, P= 0.002) blood pressures reduced on day 14 in the treatment group, compared with the baseline values, whereas no effects were observed with LIFU treatment or cationic microbubbles injection alone. Canines treated with this strategy exhibited no local or systemic adverse events. Thus, LIFU-mediated gene delivery to CBs successfully modulated CB function and reduced blood pressure in a canine model, suggesting a new possibility for treating hypertension and further clinical translation.
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