The Relationship Between The Serum HDL Component ApoCⅢ And Coronary Heart Disease And Its HDL Proinflammatory Response And The Effect Of Statin Therapy On It

Part Ⅰ. The association of HDL-apoCIII with coronary heart disease and the effect of statin treatment on it BackgroundAs an important carrier of reverse cholesterol transfer (RCT), high density lipoprotein (HDL) is considered as a protective factor of cardiovascular system. Many epidemiological and clinical studies had found that CHD has a reverse association with the HDL cholesterol (HDL-c) level, and has a positive relationship with low density lipoprotein cholesterol (LDL-c). As a kind of effective lipid-lowing drug, statins can protect cardiovascular by lowing atherogenic lipids and anti-inflammation response.Following the development of CHD researching, it is found that not all the CHD patients had high level of LDL-c and or low level of HDL-c. And the function of HDL was also associated with its component and the pathophysiologic state of organism, and CHD also had association with the change of components of HDLs, not only with the level of plasma HDL simply. For example, HDLs of patients with CHD or end-stage kidney disease had pro-inflammatory or pro-apoptotic effect. Recent study found that, the apolipoprotein CIII (apoCIII) content in HDL (HDL-apoCIII) was higher in CHD patients, and it can predict CHD better. However, because of the widely use of statin drugs, it is still unclear about the relationship between HDL-apoCIII and CHD and the effect of statin treatment on it.Objectives1. To establish the relationship between HDL-apoCIII and CHD.2. To study the effect of statin treatment on HDL-apoCIII and its association with CHD and lipids in plasma.MethodsWe enrolled 120 CHD patients and 80 non-CHD patients according to angiographic examination. All the CHD patients received statin treatment, and were followed after three month treatment. The patients’information and blood sample were collected, the HDL samples of all the patients and followed CHD patients were isolated from plasma by an ultracentrifugation method, and the apoCⅢ concentrations of all the blood and HDL samples were tested. The association of HDL-apoCⅢ with CHD and the effect of statin treatment on it were analyzed by statistic methods.Results1. In the study we found that, CHD patient had a significantly higher HDL-apoCⅢ than non-CHD patients (25.05±12.98μg/mgHDL vs 21.00±11.33 μg/mgHDL,p<0.05). After adjusting the effect of other variables, HDL-apoCIII was still a significant independent risk factor of CHD (p<0.05).2. Although statin reduced the atherogenic lipids and increased HDL-c in CHD patients, it also significantly increased HDL-apoCⅢ (24.26±14.80 μg/mgHDL vs 29.35± 16.46 μg/mgHDL, p<0.05) at the same time.3. HDL 组分 apoCⅢ had a significant association with TG level in non-CHD patients (R=0.62, p<0.05), and this relationship was weaker in CHD patients (R=0.24, p<0.05), and disappeared in the CHD patients after statin treatment (R=0.11,p>0.05). The association between HDL-apoCⅢ and plasma apoCⅢ was not affected by disease state or statin treatment, it was still significant in non-CHD (R=0.35,p<0.05), CHD (R=0.31, p<0.05) patients, or the CHD patients after statin treatment (R=0.35,p<0.05).4. As a part of the theory of lipids transfer, we did not find a significant association between HDL-apoCⅢ and HDL-c or LDL-c in this study.Conclusions1. CHD patients have a significant higher HDL-apoCⅢ than non-CHD patients, andHDL-apoCⅢ is a good CHD predictor.2. Although statin decreased atherogenic lipids and increased HDL-c in CHD patients, it also increased HDL-apoCⅢ at the same time.Part Ⅱ. The effect of apoCⅢ on the pro-inflammatory response of HDL of coronary heart disease patients and the effect of statin treatment on itBackgroundMany studies have found that high density lipoprotein (HDL) is not only an important carrier of reverse cholesterol transfer (RCT), it also has anti-inflammatory and anti-oxidant effect, and play an important role in protecting cardiovascular system. Studies have confirmed HDL has negative relationships with atherosclerosis (AS) and coronary heart disease (CHD), the increase of HDL level can reduce the risk of CHD.In recent years it is found that a further increase of HDL in CHD patients cannot get more heart benefit, and the function of HDL was also associated with its components and the pathophysiologic state of organism. HDLs of patients with CHD or end-stage kidney disease showed a pro-inflammatory effect on vascular cells and the increased apoCⅢ in HDL of CHD patients showed a pro-apoptotic effect on endothelial cell (EC). As a pro-inflammatory apolipoprotein, it’s still unclear if increased apoCⅢ in HDL of CHD patients also has similar effect on inflammation response. Although statin can protect cardiovascular system by lowing atherogenic lipids and its anti-inflammatory effect, it still unclear if the biological function of HDL in CHD patients could be improved after statin treatment.Objectives1. To study the time and dose independence of the pro-inflammatory response of apoCⅢ.2. To study the effect of apoCⅢ on the pro-inflammatory response of HDL of CHD patients.3. To study the effect of statin treatment on the pro-inflammatory response of HDL of CHD patients.MethodsIn this part of the study, we treated human umbilical endothelial cell (HUVEC) by apoCⅢ to evaluate the pro-inflammatory effect of apoCⅢ. We treated HUVEC by isolated HDL, and explored the effect of apoCⅢ on the inflammatory response of HDL of CHD patients by using apoCⅢ antibody neutralized the effect of apoCIII in HDL. We also compared the inflammatory response of HDL of CHD patients before and after statin treatment to evaluate the effect of statin treatment on the inflammatory response of HDL of CHD patients, and evaluated the effect of apoCIII on the inflammatory response of HDL of CHD patient after statin treatment.The secretion or expression of interleukin-6 (IL-6), monocyte chemotactic protein (MCP-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) were used to evaluate the pro-inflammatory response.Results1. ApoCⅢ promote the inflammation response in a time and dose dependent manner. Following the increase of time and concentration of apoCⅢ acted, the expression of IL-6, MCP-1, ICAM-1 and VCAM-1 were increased accordingly.2. ApoCⅢ play an important role in the inflammatory response of HDL of CHD patients. Compared with control group, the secretion or expression of MCP-1, VCAM-1 and ICAM-1 were significantly increased by HDLs isolated from CHD patients, and reduced significantly after neutralizing the effect of apoCⅢ in HDL by apoCⅢ antibody.3. Statin treatment could increase HDL-c level, but it had no obvious effect on the pro-inflammatory effect of HDL of CHD patients, and apoCⅢ still play an important role in the inflammatory response of HDL of CHD patients after statin treatment.Conclusions1. The pro-inflammatory effect of apoCⅢ had a time and dose dependence.2. ApoCⅢ play an important role on the pro-inflammatory response of HDL of CHD patients.3. Statin treatment couldnot improve the pro-inflammatory effect of HDL significantly, apoCⅢ still plays an important role in the pro-inflammatory response of HDL in CHD patients after statin treatment.Conclusions of the study(1) HDL-apoCⅢ has a positive relationship with CHD, and it’s a good CHD predictor;(2) Although statin treatment can increase HDL-c level in CHD patients, it also increased HDL-apoCⅢ;(3) ApoCⅢ is a kind of apolipoprotein with pro-inflammatory effect, and it can promote inflammatory response in time and dose dependent manner;(4) ApoCⅢ play an important role in the pro-inflammatory response of HDL of CHD patients. Although statin has strong anti-inflammation effect, it could not improve the pro-inflammatory effect of the HDL of CHD patients, and apoCⅢ was still an important factor in the process of inflammatory response of HDL of CHD patients.(5) This study confirmed the associations of HDL-apoCⅢ with the biological function of HDL and CHD, and indicated a new target and point for evaluating the biological function of HDL and the effect of statin treatment.