Effect Of Renal Denervation On The Expression Profile Of Circular RNA In The Serum Of Patients With Resistant Hypertension

Objective: RDN provides a new treatment option for patients with resistant hypertension(RH)who have failed drug treatment.Although studies have shown that reduced sympathetic nerve activity in patients after RDN is the main cause of blood pressure decline.However,the epigenetic regulators are involved in the treatment mechanism of RDN is still beyond our knowledge.Recently,circ RNAs have emerged as critical epigenetic regulators in various pathophysiological processes.Methods: In this study,inpatients with RH were recruited,between March 2019 to March 2020,from the First Affiliated Hospital of Fujian Medical University(Fujian,China).The serum samples of patients with RH were collected before and 48 h after RDN.We explored the mechanism underlying RDN with high-throughput integration of circular RNA(circ RNA)data.Results: Through the expression of circ RNA,we discovered a total of 338 circ RNAs to be differentially before and atfer RDN.Of these,170 were upregulated and 168 downregulated after RDN(fold ≥1.2 and P < 0.05).Among them,5 changed significantly(fold ≥1.5 and P < 0.05).We used Real-time quantitative PCR to detect these 5 circ RNA before and after RDN in patients with RH to verify our results.We found that hsa＿circ RNA＿000367 were upregulated and hsa＿circ RNA＿405119downregulated after RDN(P < 0.05)and predicted their downstream mi RNA-m RNA network and analyzed their putative function via circ RNA-mi RNA-m RNA pathway.their functional annotation may be related to nerve injury and hypertension by using Gene Ontology/Kyoto Encyclopedia of Genes and Genomes(GO/KEGG)analysis.The most highly enriched biological process,cellular component and molecular function for predicting target gens from hsa＿circ RNA＿000367 were positive regulation of telomerase RNA localization to Cajal body,ATP hydrolysis coupled transmembrane transport,peptidase activity;The most significantly enriched pathways of these predicting target gens from hsa＿circ RNA＿000367 were protein digestion and absorption,phagosome.The most highly enriched biological process,cellular component and molecular function for predicting target gens from hsa＿circ RNA＿405119 were acute inflammatory response(includes positive regulation of tumor necrosis factor secretion and humoral immune response),protein secretion,protein binding.The most significantly enriched pathways of these predicting target gens from hsa＿circ RNA＿405119 were complement and coagulation cascades,regulation of actin cytoskeleton,focal adhesion.The intersection between the predicted target gene and sympathetic nerve related genes is CORO1 A,FN1,GCG,TMSB15 A,TPH1,ALOX5 AP,MAGEL2 and VIM.Conclusions: The mechanism underlying RDN may be closely related to upregulate hsa＿circ RNA＿000367 or downregulated hsa＿circ RNA＿405119 involved regulate multiple pathways and multiple cellular and molecular biological processes.It and can potentially be used as treatment effect biomarkers in RDN.