Investigation On Correlation Between The Imbalance Of Redox Status And Carotid Artery Atherosclerosis,Coronary Narrowing And The Potential Remedying Value By Correcting The Imbalance Of Redox Status

Objective The oxidative stress has been admitted to be deeply involved in the initiation and development of atherosclerosis, which is recognized as a very important mechanism for pathogenesis of atherosclerosis. Some researches in multi-centers with big quantity of samples, however, didn't show expectant results by the remedy of anti-oxidative medicines, the explanation for it is still plausible and ambiguous by now. But our view is that the redox status of our body is a dynamic process, without care of the underlying deviation of redox status, a "fixed routine dosage" of anti-oxidative vitamins may not fit all the situation, and cause the results deviated from the expectation. So to identify that whether a deviation of redox status is really in a patient suffering from atherosclerosis and the degree of deviation, and then to investigate the potential correlation between the deviation of redox status and the pathogenesis of atherosclerosis, so that to set up a remedy for atherosclerosis against oxidative stress-induced injury based on correction of the deviation of redox status may be more reasonable.But to distinquish the atherosclerotic locus in artery intima from the surrounding soft tissues and to detect the actual injurious state of atherosclerosis is quite difficultly in clinical investigation, especially in coronary artery, which is in a fast and non-stop beating state, and this has been a essential technical obstacle impeding the study for correlation between the deviation of redox status and the pathogenesis of atherosclerosis. The examinations with ECG and ECT myocardial perfusion developing just show the injury results by atherosclerosis, cannot reflect the actual state of atherosclerosis sensitivily. Recently the carotid intima-media thickness(CIMT) by high frequency ultrasonic examination is considered quite accurate for measurement of the actual state of atherosclerosis, and is a good and non-invasive method for monitoring the atherosclerosis. But the carotid IMT is not the coronary IMT, whether the CIMT is a good index for coronary atherosclerosis? regarding the monitoring CIMT for reflecting the coronary IMT, some researche's have reported positive results, but the simultaneous study of CIMT, coronary arteriography and redox status has not been reported.The primary treatment for atherosclerosis is lipid-reducing remedy up to now. Beside lipid-reducing effect, the Xuezhikang however, possesses additional effects of redox status modulation and endothelial protection, whether can it produce better anti-atherosclerotic effects compared to drug with equal validity but mere lipid-reducing effect? To clarify it may help for proving the intrinsic correlation between the deviation of redox status and the pathogenesis of atherosclerosis.So, 376 hospitalized patients in cardiovascular section were enrolled in this prospecting study, including: The deviation of reduced form glutathione/oxidized form glutathione (GSH/GSSG) redox status and CIMT; The coronary narrowing and the CIMT,the deviation of GSH/GSSG redox status; The correlation between the clinical amelioration of coronary heart disease(CHD) and the modulation of GSH/GSSG redox status and endothelial protection besides the lipid-reducing effects granted by Xuezhikang.Methods 167 hospitalized patients were examined with high frequency ultrasonography on carotid artery, and then divided into three groups according to their carotid intima-media thickness, 79 patients fell into plaque-forming group(A), 52 cases was carotid artery intima-thickning group(B),and 36 cases was group (C) with normal CIMT. All patients had their plasma glutathione (reduced form GSH and oxidized form GSSG), nicotinamide adenine dinucleotide phosphate (reduced form NADPH and oxidized form NADP~+), oxidized low density lipoprotein (oxLDL) and malondialdehyde (MDA) been measured. The GSH/GSSG and NADPH/NADP~+ redox potential were calculated according to Nernst equation, and the correlations of two redox potentials with the CIMT and oxLDL was analyzed.97 hospitalized patients were examined with coronary arteriography, and then divided into three groups according to their coronary narrowing degree, 42 cases with coronary narrowing over 50% in any main branch of coronary artery fell into group with coronary heart disease(A); 32 cases with coronary narrowing between 0%-50% in any main branch of coronary artery fell into group with preclinical coronary heart disease(B); and 23 cases without coronary narrowing fell into control group(C). The simultaneous tests for CIMT, GSH/GSSG, GSH/GSSG potential were performed. Then the accounting records based on respective coronary arteriography and CIMT were analyzed for correlations between the CIMT and coronary narrowing and GSH/GSSG redox status.112 hospitalized patients with CHD were randomly divided into two groups, who were treated by Xuezhikang (56 cases) or Cholestyramine (56 cases) for 8 weeks respectively. The total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG), nitric oxide (NO), endothelin-1 (ET-1), GSH and GSSG were measured before and after treatment, the GSH/GSSG redox potential was calculated according to Nernst equation. The clinic and ECG amelioration were recorded and analyzed for correlation with the GSH/GSSG redox status.Results Along with the thickening of carotid artery intima (from Group C to Group A), GSH, GSH/GSSG gradually reduced and GSSG, GSH/GSSG redox potential gradually inc+reased (more positive) (P<0.05), and the NADPH and NADPH/NADP redox status also showed similar but milder changes. The products of oxidative stress-oxLDL and MDA also increased significantly along with the thickening of artery intima (P<0.05). The analysis for relationship between GSH/GSSG redox potential and oxLDL showed significant and positive correlations(P<0.05), and the redox status shifted to oxidizing direction along with the carotid intima thickening and plaque-forming. In the investigation for CIMT and coronary arteriography, the correlation of coronary narrowing with CIMT,plaque-records,plaque-forming incidence in group A is higher than in group B, and group B is higher than group C, their correlations are still high positive. Because the CIMT is a non-invasive measurement, so the strong correlation of coronary narrowing and CIMT may provide a convenient and accurate way for early diagnosis,treatment and prognosis of coronary heart disease. Along with the C→B→A groups, the GSH/GSSG redox status also shifted to oxidizing direction, which further proved that the GSH/GSSG redox status was a sensitive and reliable parameter for oxidative stress in atherosclerosis.The 8 weeks treatment with xuezhikang or cholestyramine produced similar decrease of TC, LDL-C in both groups, but the xuezhikang showed amelioration for deviation of GSH/GSSG redox status and endothelial functios. The GSH,GSH/GSSG ratio increased significantly (P<0.01), GSSG and GSH/GSSG redox potential decreased significantly in xuezhikang group (P <0.05), ET-1 decreased (P <0.05), and NO and NO/ET-1 ratio increased significantly (P <0.01). Total efficacy rates in relieving angina symptom and improving ECG parameters in xuezhikang group were 92.7% and 76.4%, compared with the cholestyramine group of 77.4% and 58.5% respetively (P<0.05). The above results further indicated that the deviation of GSH/GSSG redox status may be deeply involved in the pathogenesis of atherosclerosis and coronary heart disease, and the lipid-reducing drugs with complementary effects for modulating GSH/GSSG redox status and endothelial function may be potent benificial for anti-atherosclerosis.Conclusion The deviation of GSH/GSSG redox status to oxidization was highly correlated with carotid intima thickening,plaque-forming and coronary narrowing. The high frequency ultrasonography can clearly illustrate the carotid atherosclerotic locus, and accurately prodict the coronary atherosclerotic injuries, the carotid plaque records and coronary narrowing records are strong correlated with each other (r=0.723, p<0.01), which suggested a valuable signifecance of CEVIT in CHD screenig, early diagnosis,treatment, and prognostic judgement. The lipid-reducing drug of xuezhikang demonstrated better clinical effects for CHD than cholestyramine, which showed similar lipid-reducing effect, but without complementary effects for modulating GSH/GSSG redox status and endothelial function. All the above results may indicate a deep implication of deviation of GSH/GSSG redox status in the pathogenesis of atherosclerosis and CHD, and the remedy for modulating GSH/GSSG redox status could be a good alteration for treating atherosclerosis and CHD.