Abstract
The aim of the present study was to investigate the role of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) in determining the size distribution of high density lipoproteins (HDL) in human plasma. Whereas both purified CETP and PLTP preparations were able to promote the size redistribution of isolated HDL3, CETP favored the emergence of small HDL, while PLTP induced the formation of both small and large conversion products. When the total plasma lipoprotein fractions isolated from nine distinct subjects were incubated for 24 h at 37 degrees C with either purified PLTP or purified CETP, significant alterations in the relative proportions of the five distinct plasma HDL subpopulations, i.e., HDL2b (9.71-12.90 nm), HDL2a (8.77-9.71 nm), HDL3a (8.17-8.77 nm), HDL3b (7.76-8.17 nm), and HDL3c (7.21-7. 76 nm) were also observed. PLTP induced a significant increase in the relative abundance of HDL2b (8.66 +/- 2.34% versus 7.87 +/- 1. 83% in controls; p < 0.01) and a significant decrease in the relative abundance of HDL3a (32.76 +/- 3.42% versus 37.87 +/- 2.62% in controls; p < 0.05). In contrast, CETP significantly reduced the relative proportion of HDL2a (33.03 +/- 2.53% versus 37.56 +/- 6.43% in controls; p < 0.01) but significantly increased the relative proportion of both HDL3b (21.36 +/- 6.97% versus 15.58 +/- 7.75% in controls; p < 0.01) and HDL3c (3.21 +/- 4.84% versus 1.13 +/- 0.56% in controls; p < 0.05). Finally, in order to assess further the physiological relevance of in vitro observations, CETP activity, PLTP activity, and HDL size distribution were determined in plasmas from 33 alcoholic patients entering a cessation program. Alcohol withdrawal was associated with (i) a significant increase in plasma CETP activity (173.5 +/- 70.5%/h/ml before versus 223.2 +/- 69. 3%/h/ml after alcohol withdrawal, p = 0.0007), (ii) a significant reduction in plasma PLTP activity (473.9 +/- 203.7%/h/ml before versus 312.7 +/- 148.4%/h/ml after alcohol withdrawal, p = 0.0001), and (iii) a significant shift of large HDL2b and HDL2a toward small HDL3b and HDL3c. On the one hand, changes in plasma CETP activity correlated negatively with changes in the proportion of HDL2a (r = -0.597, p = 0.0002) and positively with changes in the proportion of HDL3b (r = 0.457, p = 0.0075). On the other hand, changes in plasma PLTP activity correlated positively with changes in the proportion of HDL2b (r = 0.482, p = 0.0045) and negatively with changes in the proportion of HDL3a (r = -0.418, p = 0.0154). Taken together, data of the present study revealed that plasma PLTP and CETP can exert opposite effects on the size distribution of plasma HDL. PLTP can promote the formation of HDL2b particles at the expense of HDL3a, while CETP can promote the formation of HDL3b particles at the expense of HDL2a.
Highlights
§ To whom correspondence should be addressed: Laboratoire Central de Biochimie Medicale, Hopital du Bocage, 21034 Dijon, France
Isolated HDL3 were incubated for 24 h at 37 °C in the presence or absence of either cholesteryl ester transfer protein (CETP) or phospholipid transfer protein (PLTP), which were partially purified from total human plasma as described under “Materials and Methods.”
While the relative abundance of HDL3a and HDL3b was reduced in the presence of either CETP or PLTP, some differences were observed between the two conversion processes
Summary
§ To whom correspondence should be addressed: Laboratoire Central de Biochimie Medicale, Hopital du Bocage, 21034 Dijon, France. The presence of coronary artery disease was more strongly associated with abnormalities in HDL particle size distribution than with low HDL cholesterol levels [2]. These observations raised a considerable interest in identifying the factors that can induce alterations in the relative proportions of plasma HDL2b, HDL2a, HDL3a, HDL3b, and HDL3c subfractions in vivo. Complementary studies demonstrated that PLTP can act as an HDL conversion factor in the absence of other lipoprotein fractions by promoting the formation of large and small HDL subfractions from an initial population of HDL with intermediate size (14 –16). It appears that both CETP and PLTP can promote the size redistribution of HDL particles, and might account in vivo for the heterogeneity in the size and composition of the plasma HDL fraction
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