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Heart failure (HF) has been proposed as a potential indication of renal denervation (RDN). However, the mechanisms enabling RDN to attenuate HF are not well understood, especially the central effects of RDN. The aim of this study was to decipher the mode of operation of RDN in the treatment of HF using a canine model of right ventricular rapid pacing-induced HF. Accordingly, 24 Chinese Kunming dogs were randomly grouped to receive sham procedure (sham-operated group), bilateral RDN (RDN group), rapid pacing to induce HF (HF-control group), and bilateral RDN plus rapid pacing (RDN + HF group). Echocardiography, plasma brain natriuretic peptide (BNP), and norepinephrine (NE) concentrations of randomized dogs were measured at baseline and 4 weeks after interventions, followed by histological and molecular analyses. Twenty dogs completed the research successfully and were enrolled for data analyses. Results showed that the average optical density of renal efferent and afferent nerves were significantly lower in the RDN and RDN + HF groups than in the sham-operated group, with a significant reduction of renal NE concentration. Rapid pacing in the RDN + HF and HF-control groups, compared with the sham-operated group, induced a significant increase in left ventricular end-diastolic volume and decrease in left ventricular ejection fraction and correspondingly resulted in cardiac fibrosis and dysfunction. Cardiac fibrosis evaluated by Masson’s trichrome staining and the expression of transforming growth factor-β1 (TGF-β1) were significantly higher in the HF-control group than in the sham-operated group, which were remarkably attenuated by the application of the RDN technique in the RDN + HF group. In terms of central renin–angiotensin system (RAS), the expression of angiotensin II (AngII)/angiotensin-converting enzyme (ACE)/AngII type 1 receptor (AT1R) in the hypothalamus of dogs in the HF-control group, compared with the sham-operated group, was upregulated and that of the angiotensin-(1-7) [Ang-(1-7)]/ACE2 was downregulated. Furthermore, both of them were significantly attenuated by the RDN therapy in the RDN + HF group. In conclusion, the RDN technique could damage renal nerves and suppress the cardiac remodeling procedure in canine with HF while concomitantly attenuating the overactivity of central RAS in the hypothalamus.

Rubber trees (Hevea brasiliensis) were successfully introduced to south China in the 1950s on a large-scale; however, due to the climate, are prone to cold injury during the winter season. Increased cold tolerance is therefore an important goal, yet the mechanism underlying rubber tree responses to cold stress remains unclear. This study carried out functional characterization of HbICE1 (Inducer of CBF Expression 1) from H. brasiliensis. A nucleic protein with typical features of ICEs, HbICE1 was able to bind to MYC recognition sites and had strong transactivation activity. HbICE1 was constitutively expressed in all tested tissues, with highest levels in the bark, and was up-regulated when subjected to various stresses including cold, dehydration, salinity and wounding. When overexpressed in Arabidopsis, 35S::HbICE1 plants showed enhanced cold resistance with increased proline content, reduced malondialdehyde (MDA) metabolism and electrolyte leakage, and decreased reactive oxygen species (ROS) accumulation. Expression of the cold responsive genes (COR15A, COR47, RD29A, and KIN1) was also significantly promoted in 35S::HbICE1 compared to wild-type plants under cold stress. Differentially expressed genes (DEGs) analysis showed that cold treatment changed genes expression profiles involved in many biological processes and phytohormones perception and transduction. Ethylene, JA, ABA, as well as ICE-CBF signaling pathways might work synergistically to cope with cold tolerance in rubber tree. Taken together, these findings suggest that HbICE1 is a member of the ICE gene family and a positive regulator of cold tolerance in H. brasiliensis.