Plasma Levels Of Peroxynitrite, Adiponectin And Tumor Necrosis Factor α In Patients With Hyperlipemia During The Different Stages

BackgroundHyperlipidemia is the condition of abnormally elevated levels of any or alllipids and/or lipoproteins in the blood. Hyperlipidemia, especiallyhypercholesterolemia is regarded as a modifiable risk factor for cardiovasculardisease due to their influence on vascular endothelium. Oxidative stress is one ofthe mechanisms that cause vascular endothelial dysfunction. Peroxynitrite(ONOO~-) is prepared by the reaction of nitric oxide with superoxide. Because ofits oxidizing and nitrating properties, peroxynitrite can damage a wide array ofmolecules in cells including DNA and proteins, which cause oxidative stress andtissue damage in the vascular endothelium. Adiponectin is an adipocyte-derived cytokine, which is abundantly presentin the circulation. Evidence suggests that adiponectin has anti-atherogenicproperties by improving endothelial function and having anti-inflammatoryeffects in the vascular wall. After post-translational modifications, adiponectin issecreted into the circulation in three different multimers:a low molecularweight(LMW) form, a middle molecular weight(MMW) form and a highmolecular weight (HMW) form but the biological importance of each one ofthese isoforms is still unclear. Tumor necrosis factor alpha(TNF-α) is anotheradipocyte-derived cytokine, which promote adhesion molecule expression andrecruitment and activation of inflammatory cells. Moreover, TNF-α is cruciallyinvolved in the pathogenesis and progression of atherosclerosis through the effecton lipid metabolism.Our previous studies found that inflammatory cytokine TNF-α andendothelium injury factor ONOO~-were both elevated in hyperlipidemia rats,which were depressed by adiponectin. Then, what would happen in the humanbeings? Did these factors play an important role in the progress of atherosclerosisespecially in the patients with hyperlipemia and coronary heart diseases?However, it is not clear now how plasma levels of ONOO~-, adiponectin andTNF-α change in patients with hyperlipemia.AimsThe aims of the current study were aim to investigate the change andcorrelation of plasma levels of ONOO~-, total adiponectin, three subtypes ofadiponectin and TNF-α in patients with different level of hyperlipemia, in exploring the vascular endothelial damage and adiponectin regulation, provided anew basis for the prevention and treatment of atherosclerotic cardiovasculardisease.MethodsThe study population consisted of male patients admitted to the Departmentof Geriatrics in Xijing Hospital, the Fourth Military Medical University of China,within the period from January2010to December2010. In this study,50malepatients with borderline high LDL-C level and50patients with CHD andhypercholesterolemia, and40normal controls were included. Patients withborderline Subjects and controls were matched for gender, and body mass index(BMI). Plasma levels of nitrotyrosine(NT), APN and TNF-α were detected byELISA respectively.Results1. There was no significant difference between HL group, HCHD group, andCON group in age, body mass index, blood pressure, blood glucose,triglycerides, high density lipoprotein and glycosylated hemoglobin. Theplasma level of LDL-C in the HL group was significantly higher than that incontrol subjects. The plasma level of LDL-C and total cholesterol in theHCHD group were both significantly higher than those in the HL group..2. Compared to the control group, plasma NT concentration was higher in theHL group and was further increased in the HCHD group. The level of TNF-α was decreased in the HL group while increased in the HCHD group comparedwith the control group.3. Compare with the control group， the plasma level of total APN wassignificantly increased in the HL group while decreased in the HCHD group.Moreover, the plasma levels of HMW and MMW were increased in HL group,but they were decreased in HCHD group, however, the plasma level of LMWis decreased in both HL and HCHD group.4. In the HL group, LDL-C was correlated positively with total APN(r=0.793，P<0.01), HMW(r=0.815， P<0.01), MMW(r=0.668， P<0.01) andNT(r=0.909， P<0.05). TNF-α was correlated negatively with totalAPN(r=-0.539，P<0.01), HMW(r=-0.674，P<0.01), MMW(r=-0.526，P<0.01),however, it was correlated positively with LMW(r=-0.526，P<0.01).5. In the HCHD group, LDL-C had no correlated with any type of APN(P>0.05),and TNF-α also had no correlated with any type of APN(P>0.05).Conclusion1. For the first time, we found that in patients with dyslipidemia to a lesserextent in the LDL-C edged level, NT (ONOO~-markers) in the plasma levelswere significantly increased, suggesting that patients may appear toendothelial oxidative/nitrification stress injury, accompanied by increasingcompensatory secretion of adiponectin, while suppressing the generation ofinflammatory factor TNF-α in this process.2. In the more severe hypercholesterolemia patients with coronary heart disease, the plasma NT (ONOO~-markers) and TNF-α levels were significantlyincreased, but adiponectin levels were significantly decreased, this suggestingthat adiponectin secretion reduced, and oxidation/nitration damage andinflammatory response is further increased, leading to coronaryatherosclerosis injury.3. In the three different molecular weight forms of plasma total adiponectin,HMW and MMW may play a major role of vascular protection.