A Study On The Impact Of Altitude Hypoxia On The Concentration Of NADPH Oxidase And CaMK â…¡ In Hypertension And Heart Failure Patients And Genetic Polymorphism

Objective:To explore the relationship between hypertension and heart failure diseases and thelevels of NADPH oxidase,CaMKII and gene polymorphism. In order to understand themolecular mechanism,and provide a new strategy for the treatment of heart failure,Method:To Select345patients with essential hypertension(EH), all the patients were dividedinto A group and B group depending on the residence. Group A, who were permanentlyresided for at least10years at an altitude of2260-3000m,were enrolled totally211patients with EH, divided into EH(130cases) and EH-HF(81cases) according to heartfailure complication;130EH, including EH1(40cases), EH2(46cases) and EH3(44cases)according to different blood pressure levels;81EH-HF, including EH-HF1(37cases)EH-HF2(36cases) and EH-HF3(8cases); Group B, who were permanent residence atan altitude>3000m at least10years, were enrolled totally74patients with EH and60patients with EH-HF which were divided into EH-HF1(28cases)，EH-HF2(26cases) andEH-HF3(6cases). Healthy individuals living for at least10years in the altitude of2260-3000m were enrolled90cases and at an altitude>3000m were enrolled71cases ascontrol group in the same period respectively; EH-HF was divided into the EH-HF1,EH-HF2, EH-HF3three subgroups according to NYHA classification. The NADPHoxidase、CaMKII concentration were measured by Enzyme-linked immunosorbent assay(ELISA). NADPH oxidase gene polymorphism was determined by PCR-RFLP technologyand gene sequencing technology.Results:1. Serum conventrations of NADPH oxidase and CaMKII in hypertension:1.1NADPH oxidase levels of patients with hypertension were significantly higher thanthe normal controls, and increased with blood pressure grade. Compared with EH3(Altitude2260-3000m), NADPH oxidase levels in EH3(Altitude>3000m) weresignificantly higher；1.2Compared with Control group、EH1、EH2，Serum CaMKII concentrations in EH3were significantly increased，CaMKII levels in EH3(Altitude>3000m) were significantlyhigher than EH3(Altitude2260-3000m)；2Serum concentrations of NADPH oxidase and CaMKII in hypertension and heartfailure:2.1Compared with control group and EH3, NADPH oxidase levels in EH3-HF wassignificantly increased in an altitude of2260-3000m, and Compared with control group,Serum CaMKII concentration in EH3-HF were also significantly increased. But both ofthem no correlation with the degree of heart failure classification.2.2Compared with control group, the levels of NADPH oxidase and CaMKII inEH3-HF were significantly higher in an altitude>3000m, and both of them were increasedwith heart failure classification, but not significantly.2.3The levels of NADPH oxidase and CaMKII in EH3-HF in different altitudes werenot significantly different.3Determination of gene polymorphism3.1CYBAC242T genotype frequencies in every group were in line with theHardy-Weinberg genetic equilibrium;3.2Compared with the control group (64.4%,73.2%), CC (79.5%,91.9%) inEH in the two altitudes were higher (P <0.05). the constitute of CC in EH-HF(91.4%) in altitude of2260-3000m increased as Compared with the control group(64.4%)and EH (79.5%). the constitute of CC in EH-HF (93.3%) in altitude of above3000mincreased as Compared with the control group.(73.2%). So the distribution frequency ofCC in EH and EH-HF groups were significantly higher.3.3According to logistic analysis:in altitude2260-3000m,CCgenotype wereassociated with EH(OR=2.133,P<0.05)and EH-HF(OR=5.664,P<0.05);in anAltitude>3000m,CC genotype correlated with EH(OR=3.014,P<0.05),andEH-HF(OR=5.115,P<.05),and C gene associated with both of EH andEH-HF(OR=2.703,4.480,P<0.05),therefore we think CC or C genes were susceptibilitygenes of EH and EH-HF.3.4NADPH oxidase levels in CC genotype were higher than CT(P<0.05) and TT(p>0.05), CaMKII levels of CC genotype were higher than CT(P>0.05) andTT(p<0.05).Conclusions1. The levels of NADPH oxidase and CaMKII were significantly changed inhypertension at high altitude, they may have a considerable impact on the produce anddevelopment of hypertension, and were seriously associated with the levels of bloodpressure.2.Serum levels of NADPH oxidase and CaMKII in hypertension with heart failurewere significantly increasing than pure hypertension patients and normals, it suggested thetwo factors participated in emerging and progress of hypertension with heart failure.3.Patients possessing CC of gene C242T CYBA had higher serum concentration ofNADPH oxidase and CaMKII than other two genes(CT/TT), demonstrating CC wasindependent risk factors to suffer hypertension and heart failure.