The Influence Of High Glucose On HUVECs Prorenin Expression And The Preliminary Mechanism

Background:Renin-angiotensin system(RAS) resulted in atherosclerosis(AS) through oxidantstress, the elevation of blood pressure, inflammation and endothelial dysfunction, evenmore, it has close correlation with hypertension, diabetes mellitus, heart failure, chronicrenal disease, cerebrovascular disorder. People detected that, the local RAS exerts onmultiple organs, such as pancreas, heart, kidney, vascular system, adipose tissue andnervous tissue. RAS also has the haemodynamic effect, including mediate cell growth,differentiation, proliferation and apoptosis, also mediate the generation of ROS, tissueinflammation reaction and hormone secretion. Recent years, scholars conclude thatthere exists the renin, prorenin and (pro)renin receptor in RAS, renin synthesis Angindependently of the circulatory RAS, which may happens in the kidney. RAS maygenerate the biological effect independent of AngII, which prompt that the ARB andACEI may have limitations under the hyper-glucose. The prorenin is synthesised in thekidney, the plasma concentration is10fold higher than renin. The renin binding to the(pro)renin-receptor resulted in the conformational change of renin, has the enzymaticactivity. The increasing of the blood glucose enhanced the activation of RAS obviously,which induced the endothelial dysfunction and inflammation. The incompatible RASmay be the one of the regulatory mechanism which results in the endothelialdysfunction of the diabetics, which may result in the large vessels and capillarycomplication of diabetes mellitus. The prorenin level in blood plasma the diabeticsaccompany with capillary complication is higher than normal, which maybe the partialresult of the RAS unbalance. Abundant clinical research demonstrated that, local orintegrated RAS unbalance play a significant role in diabetic chronicity complication,thus mediating RAS is an important path to prevent and cure the diabetic complication. Endotheliocyte plays a significant role in controlling the atherosclerosis pathogenesisand vascular tone, and endothelial dysfunction is one of the earliest pathological changeof the hyperlipermia, diabetes, smoking and hypertension, and these are important riskfactors which lead to the coronary artery disease. Therefore, the precisely mechanism ofthe high glucose causes the endothelial dysfunction is not clear yet. The endothelialfunctional disorder is the main initiating factor of diabetes complicating the largevessels and capillary diseases. While the organism is stimulated by the causative agent,endotheliocyte will trigger the crucial inflammation component, including hypertonicity,leukocytosis, and inflammation cell activity up-regulation, which are all the pathologicmechanism of the blood vessel functional disorder.The preceding stage of the studies has demonstrated that the mRNA of theprorenin in HUVECs increased under the hyperglycemia condition, andconcentration-dependent and time-dependent. However, the mechanisms in thehyperglycemia action the expression of the prorenin is needed to be further investigated.Purpose:Culture the HUVECs in vitro to study the change of the mRNA of renin andprorenin under the hyperglycemia condition. Furthermore, to study after the blockade ofthe AT1R and AT2R, if the expression of prorenin through the conventionalAngII-dependent pathway under the hyperglycemia condition. Thereby, we can discussthe mechanism of the correlation of diabetes mellitus and atherosclerosis.Method:1. Culture the cell strain of HUVECs in vitro.2. Stimulate HUVECs with glucose in different concentration, to detect thechange of expression of mRNA in prorenin.3. Stimulate HUVECs with hyper-glucose in different time, to detect the changeof expression of mRNA in prorenin.4. Block the AT1R and AT2R with Olmesartan and PD123319respectively, toobserve the change of prorenin and the possible mechanism.Result:1. The glucose of different concentration acted on the HUVECs result in obviouschanges of mRNA of prorenin, which is concentration-dependent.2. The hyper-glucose acting on the HUVECs increased the expression of mRNAof prorenin, which is time-dependent.3. High glucose stimulates prorenin expression to increase and when AngII receptor AT1R and AT2R are blocked, prorenin expression descends, which indicatesthat high glucose stimulates endothelium prorenin expression increase may beaccomplished through the activiation of AT1R and AT2R, but the precisely mechanismneeds to be researched further.