Smoking On HDL Function

BACKGROUND AND OBJECTIVE:High density lipoprotein(HDL) promotes reverse cholesterol transport(RCT), and inhibits the oxidation of LDL and chemotaxis, thus plays important roles in many antiatherogenic pathways. The concentration of cholesterol carried on HDL particles (HDL-C) has been the main metric for the HDL levels in the blood. The inverse relationship between HDL-C levels and the risk of coronary heart disease (CHD) is well documented, so people made raising HDL-C levels as a target of the antiatherogenic treatment. But recently, we found that the HDL had two faces:HDL from healthy people is most often antiinflammatory, however, when systemic inflammation is present, HDL can become compromised or even proinflammatory. We now realize that HDL qualities are as important as, or more important than, the quantity.Cigarette smoking is a well-known risk factor for the development of cardiovascular disease. It’s associated with the elevated total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) levels, and decreased HDL levels. But the relationship between smoking and functional properties of lipoproteins is still unknown yet. Our study is to find out whether the HDL function changes during the acute phase and chronic phase of smoking, if so, how does it happened?METHODS:1. We involved8non-smokers and12chronic smokers, serum and plasma were collected from these healthy age-matched subjects, and divided the blood samples into3groups:non-smokers, once smokers, and chronic smokers;2. HDL was isolated by ultracentrifugation, from serum of both healthy non-smokers’ and chronic smokers’ samples;3. The concentration of Serum Amyloid Protein A (S AA) on the HDL was measured by ELISA method;4. Oxidative levels and oxidative affectabilities of LDL and HDL was evaluated by detecting the optical density(OD,234nm) and calculating the OD at baseline and the time at the max oxidative velocity;5. Anti-oxidative fuction was evaluated by detecting the OD (234nm) and calculating the lag time(Tlag) of oxidation of the LDL incubated with HDL samples, with oxidative stress provided by Cu2+;6. The serum PON-1activity was measured by fluorometric method; 7. The effect of LDL on the chemotaxis of THP-1cells was assessed by the Transwell cell chambers;8. The effect of HDL on the chemotaxis of THP-1cells was assessed by the Transwell cell chambers.RESULTS:1. The ages(37±7.6y v.s.36±7.1y, p=0.87) and BMIs(22.9±0.76v.s.22.8±0.48, p=0.67) of the subjects were matched;2. During the acute phase of smoking, the systolic blood pressure (120.6±10.5mmHg v.s.106.9±12.5mmHg, p<0.01), the pulse pressure(42.5±6.0mmHg v.s.31.9±4.6mmHg, p<0.01), the heart rate (84±4bpm v.s.68±6bpm, p<0.01), and the ALT level increased significantly (28.98±12.04U/L v.s.26.49±12.61U/L, p<0.01), and diastolic blood pressure (DBP), AST and GLU had the tendency to increase. During the chronic phase, pulsepressure (PP) increased significantly(38.3±7.8mmHg v.s.31.9±4.6mmHg, p=0.02),the levels of TBil (10.27±3.70umol/Lv.s.14.13±4.24umol/L, p=0.04) and Dbil (3.39±1.06umol/Lv.s.4.70±1.51umol/L, p=0.03) decreased significantly;3. During the acute phase of smoking, the concentration of SAA on HDL increased ignificantly (15.66±7.8ng/μg v.s.10.10±4.8ng/μg, p=0.0067). During the chronic phase, the concentration of SAA on HDL was significantly lower than in the actute phase (7.75±2.1ng/μg v.s.15.66±7.8ng/μg, p=0.0034);4. During the chronic phase, the OD of LDL at baseline was elevated significantly (0.28±0.06v.s.0.21±0.03, p=0.01);5. During the chronic phase, the time of LDL at the max oxidative velocity decreased significantly (40.5±9.3min v.s.53.8±12.5min, p=0.016);6. During the acute phase of smoking, the Tlag of HDL+LDLpool showed the tendency to decrease (87.3±5.8min v.s.91.6±7.7min, p=0.093), During the chronic phase, the Tlag of HDL+LDLpool increased significantly (98.3±5.3min v.s.91.63±7.7min, p=0.032);7. During the acute phase of smoking, the time of HDL+LDLpool at the max oxidative velocity showed the tendency to decrease (131.3±7.4min v.s.126.3±6.4min, p=0.10), during the chronic phase, the time increased significantly (139.2±7.9min v.s.131.3±7.4min, p=0.038);8. During the acute phase and chronic phase of smoking, the serum PON-1activity did not changed significantly; 9. During the chronic phase of smoking, the THP-1chemotaxis incubated with LDL showed the tendency to increase (69±13/visual field (VF) v.s.58±13/VF, p=0.07);10. During the acute phase of smoking, the the THP-1chemotaxis incubated with HDL+LDLpool showed the tendency to increase (21±6/VF v.s.16±4/VF, p=0.09).CONCLUSIONS:1. During the acute phase of smoking, the blood pressure, the pulse pressure, the heart rate and the levels of ALT, AST, glucose, and SAA on HDL increased, demonstrated the systemic response to an acute stress and inflammatory state.2. During the acute phase of smoking, the antioxidative and anti-chemotaxis function properties of HDL were damaged, which maybe due to the significantly elevated concentration of SAA on HDL.3. During the chronic phase of smoking, the levels of antioxidants(TBil and DBil) were low, the oxidation of LDL was severe, indicated the body suffered from a heavy oxidative and inflammatory. stress. And this harzard will accumulate along time.4. During the chronic phase, the antioxidative ability of HDL increased in auto compensation of the chronic oxidative stress, and the increased oxidative affectabilities of HDL may contribute to this. But it cannot completely eliminate the effect of the chronic oxidative stress.5. During the chronic phase, the pro-chemotaxis ability of LDL increased, this maybe due to the elevated pro-inflammation property of LDL.