肺动脉高压（PH）是心血管系统疾病中的癌症，主要死于右心衰。交感神经激活致能量代谢障碍，从而活化G蛋白偶联受体激酶（Grk2）、抑制肝脏激酶B1（LKB1）活性是右心衰发生的主要机制。但Grk2和LKB1在肺动脉重构中的作用机制及其相互关系尚未见报道。我们发明的肺动脉去神经术（PADN）能抑制肺动脉重构和右心衰，但存在如下问题：肺动脉交感神经变异程度大、环形头端的PADN导管不能适于大多数极度扩大的肺动脉、缺乏预测PADN疗效的可靠指标、PADN有效的分子生物学机制不明;申请人预实验发现Grk2和LKB1在肺动脉平滑肌细胞中相互连接、 去甲肾上腺素显著激活Grk2并抑制LKB1,PADN术后左右心室纵向应变率显著增加。为此，我们拟运用算法研究、动物实验、3D磁定位标测肺动脉交感神经、改良导管设计、临床多中心随机研究、右心室功能分析和激光共振能量转移等分子生物学技术，研究肺动脉交感神经标测、优化PADN导管设计、探索PADN术有效性的机制、建立预测PADN疗效的指标体系、寻找针对Grk2-LKB1新靶点的新型药物、实现PADN术转化应用，为PH的治疗提供技术新药物

Pulmonary arterial hypertension (PH) is an incurable disease, featured by gressively increased pulmonary arterial pressure and pulmonary vessel resistance, leading to premature death induced by right ventricular failure. Overactivation of pulmonary arterial sympathetic nerves results in abnormal metabolism of energy, which activates G-protein coupling receptor kinase 2 (Grk2) with subsequent β-adrenergic receptor (β-AR) downregulation and dissentilization, inhibition of liver kinase B 1(LKB1), and right ventricular failure. However, the role of Grk2 and LKB1 in the progression of pulmonary arterial remodeling remains understudied. Pulmonary artery denervation (PADN), a novel technique innovated by our team, is reported to improve hemodynamic, to inhibit cellular synthesis and proliferation and subsequently to inhibit pulmonary artery remodeling, with resultant improvement of right ventricular function in patients with different etiologies of PH via activation of eNOS, inhibition of Akt-mTOR and p38/JNK signal pathways. Unfortunately, there are several key issues to be studied: wide discrimination in distribution of pulmonary arterial sympathetic nerves, 1st generation PADN catheter with distal circular ring not suitable for patients with severe enlarged pulmonary artery, and a lack of predicting system for ventricular function before and after PADN procedure. We found that Grk2 connected with LKB1 by co-IP technique in smooth muscle cells of pulmonary artery, PADN treatment significantly improve right ventricular longitudinal strain. Accordingly, our hypothesis is that PADN deserves its cardio-pulmonary protective effects by modulating PKA-Grk2-LKB1 signal pathway. In order to speed the translational research about PADN, the present study aims to achieve precise mapping of pulmonary arterial sympathetics and modify PADN, to analyse the safety and efficacy of PADN procedure, to create a comprehensive predictive and stratifying system based on echocardiography-derived parameters, and to identify the mechanisms correlated with PADN treatment using calculating modification, animal study, 3D magnetic mapping, optimal engineering design, measurement of right ventricular longitudinal peak systolic strain, multi-center/randomized clinical study, and molecular biological techniques. The achivement of the current study will provided a cluster of data showing the effect of PADN on patients with PH, and to identify the potential target of treating PH