Limits...
HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

Borja MS, Zhao L, Hammerson B, Tang C, Yang R, Carson N, Fernando G, Liu X, Budamagunta MS, Genest J, Shearer GC, Duclos F, Oda MN - PLoS ONE (2013)

Bottom Line: Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport.In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange.Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: Children's Hospital Oakland Research Institute, Oakland, California, United States of America.

ABSTRACT
High density lipoprotein (HDL) cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.

Show MeSH

Related in: MedlinePlus

Progression of atherosclerosis is associated with reduced HAE in rabbits.[A] HDL-ApoA-I exchange, normalized to HDL-C in rabbits fed normal rabbit chow, then switched to a high fat, high cholesterol diet (0.3% cholesterol, 4.7% coconut oil). Blood was collected at 2 months and 3 months following onset of the diet. HDL was isolated by ultracentrifugation from plasma and HAE was normalized to HDL-C concentration. P<0.0001, one-way ANOVA. [B] Atherosclerotic plaque area, as measured by histology analysis in the aortic arch. [C] Relationship between the change in HAE over months 2 and 3 on the high fat diet and the size of atherosclerotic plaque in the aortic arch. Correlation was determined by linear regression analysis using Pearson's correlation coefficient. [D] Total serum efflux capacity from J774 macrophage cells in rabbits on chow diet and after 3 months on the high fat, high cholesterol diet (P = 0.003). Statistical significance was determined by two-tailed Student's t-test.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3756009&req=5

pone-0071541-g004: Progression of atherosclerosis is associated with reduced HAE in rabbits.[A] HDL-ApoA-I exchange, normalized to HDL-C in rabbits fed normal rabbit chow, then switched to a high fat, high cholesterol diet (0.3% cholesterol, 4.7% coconut oil). Blood was collected at 2 months and 3 months following onset of the diet. HDL was isolated by ultracentrifugation from plasma and HAE was normalized to HDL-C concentration. P<0.0001, one-way ANOVA. [B] Atherosclerotic plaque area, as measured by histology analysis in the aortic arch. [C] Relationship between the change in HAE over months 2 and 3 on the high fat diet and the size of atherosclerotic plaque in the aortic arch. Correlation was determined by linear regression analysis using Pearson's correlation coefficient. [D] Total serum efflux capacity from J774 macrophage cells in rabbits on chow diet and after 3 months on the high fat, high cholesterol diet (P = 0.003). Statistical significance was determined by two-tailed Student's t-test.

Mentions: HAE of purified HDL was assessed by EPR and normalized to HDL-C to control for differences in HDL induced by diet modification. Significant impairment of HAE was observed after 2 months on the high fat, high cholesterol diet with additional loss of exchange - by 3 months (Figure 4A, P<0.0001, one-way ANOVA). Histology analysis of rabbit aortas revealed that the majority of plaque burden was in the aortic arch with significant variable lesional levels from animal to animal (Figure 4B). The degree of change in HAE between months 2 and 3 on diet correlated inversely with plaque burden in this region (Figure 4C, Pearson's r = −0.76; P = 0.03).


HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

Borja MS, Zhao L, Hammerson B, Tang C, Yang R, Carson N, Fernando G, Liu X, Budamagunta MS, Genest J, Shearer GC, Duclos F, Oda MN - PLoS ONE (2013)

Progression of atherosclerosis is associated with reduced HAE in rabbits.[A] HDL-ApoA-I exchange, normalized to HDL-C in rabbits fed normal rabbit chow, then switched to a high fat, high cholesterol diet (0.3% cholesterol, 4.7% coconut oil). Blood was collected at 2 months and 3 months following onset of the diet. HDL was isolated by ultracentrifugation from plasma and HAE was normalized to HDL-C concentration. P<0.0001, one-way ANOVA. [B] Atherosclerotic plaque area, as measured by histology analysis in the aortic arch. [C] Relationship between the change in HAE over months 2 and 3 on the high fat diet and the size of atherosclerotic plaque in the aortic arch. Correlation was determined by linear regression analysis using Pearson's correlation coefficient. [D] Total serum efflux capacity from J774 macrophage cells in rabbits on chow diet and after 3 months on the high fat, high cholesterol diet (P = 0.003). Statistical significance was determined by two-tailed Student's t-test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756009&req=5

pone-0071541-g004: Progression of atherosclerosis is associated with reduced HAE in rabbits.[A] HDL-ApoA-I exchange, normalized to HDL-C in rabbits fed normal rabbit chow, then switched to a high fat, high cholesterol diet (0.3% cholesterol, 4.7% coconut oil). Blood was collected at 2 months and 3 months following onset of the diet. HDL was isolated by ultracentrifugation from plasma and HAE was normalized to HDL-C concentration. P<0.0001, one-way ANOVA. [B] Atherosclerotic plaque area, as measured by histology analysis in the aortic arch. [C] Relationship between the change in HAE over months 2 and 3 on the high fat diet and the size of atherosclerotic plaque in the aortic arch. Correlation was determined by linear regression analysis using Pearson's correlation coefficient. [D] Total serum efflux capacity from J774 macrophage cells in rabbits on chow diet and after 3 months on the high fat, high cholesterol diet (P = 0.003). Statistical significance was determined by two-tailed Student's t-test.
Mentions: HAE of purified HDL was assessed by EPR and normalized to HDL-C to control for differences in HDL induced by diet modification. Significant impairment of HAE was observed after 2 months on the high fat, high cholesterol diet with additional loss of exchange - by 3 months (Figure 4A, P<0.0001, one-way ANOVA). Histology analysis of rabbit aortas revealed that the majority of plaque burden was in the aortic arch with significant variable lesional levels from animal to animal (Figure 4B). The degree of change in HAE between months 2 and 3 on diet correlated inversely with plaque burden in this region (Figure 4C, Pearson's r = −0.76; P = 0.03).

Bottom Line: Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport.In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange.Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: Children's Hospital Oakland Research Institute, Oakland, California, United States of America.

ABSTRACT
High density lipoprotein (HDL) cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.

Show MeSH
Related in: MedlinePlus