Feasibility Study Of MicroRNA-126 Gene Knockdown As A Novel Therapeutic Target In Primary Hypertension

ObjectiveTo observe the micro RNA-126 expression level in hypertension by mi RCURY LNA? micro RNA Arrays;Explore micro RNA-126 as a novel therapeutic target in primary hypertension.MethodsOur preliminary investigation enrolled the serum samples from 4 healthy individuals and 6 patients with essential hypertension who were comparable in age,gender,and weight,and indicated that mi R-126 expression increased in hypertension patients by mi RCURY LNA? micro RNA Arrays.The lentiviral vector containing human immunodeficiency virus 1(HIV-1),the mi R-126 gene knock down viral vector(lentimi R-126-KD),and control lentiviral vector(lenti-scramble-mi R)were constructed.Spontaneously hypertensive rats(SHR)were randomly divided into 4 groups,of which received high dose(1*108,n = 5),low dose(1*107,n = 6),scramble-mi R(5*107,n = 6),and PBS(n = 6).Lentiviral vectors were injected into the tail vein.The data on the systolic blood pressure,diastolic pressure,mean arterial pressure,and heart rate was collected weekly.After 8 weeks of virus administration,the distribution of lentiviral vectors in different tissue was observed by fluorescence microscopy.Picric acid Sirius red and HE staining were used to observe the target organ damage,ELISA kit was used to determine the serum nitric oxide(NO)content.ResultsThe lentivirus vector was constructed successfully.8 weeks after the lentiviral vector injection,green fluorescent protein(GFP)was observed in different tissue in each group.The blood pressure and heart rate did not alter significantly after lentiviral vector injection(P>0.05).Any significant differences in the heart-to-body weight ratio among the four groups were not observed of((P>0.05).Picric acid Sirius red and HE staining revealed that there was no significant difference in morphology among the four groups.A significant difference in the serum NO level among the four groups was not revealed(P>0.05).ConclusionThe hypertensive patients demonstraded significantly higher 3'-UTR of mi R-126(1.410±0.369 vs.0.838±0.274,P=0.03)and 5'-UTR of mi R-126(1.799±0.490 vs.0.997±0.437,P=0.03)expression levels compared with the healthy controls.The micro RNA-126 gene knockdown lentiviral vector was constructed successfully.Any significant antihypertensive effect was not observed by knocking down micro RNA-126 for the treatment of primary hypertension.The target organs were not protected significantly after the treatment.The increased level of micro RNA-126 expression in hypertensive patients may be due to a compensatory mechanism.