TRL, IDL, and LDL Apolipoprotein B-100 and HDL Apolipoprotein A-I Kinetics as a Function of Age and Menopausal Status

Matthan, Nirupa R; Jalbert, Susan M; Lamon‐Fava, Stefania; Dolnikowski, Gregory G.; Welty, Francine K.; Barrett, P. Hugh R.; Schaefer, Ernst J.; Lichtenstein, Alice H.

doi:10.1161/01.atv.0000172629.12846.b8

Cited by 37 publications

(32 citation statements)

References 54 publications

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“…However, this age difference is not likely to affect our results because it has been shown that apoA-I kinetic is independent of age. 34 Moreover in our study, data from the univariate and multivariate analyses clearly show that apoA-I FCR is not influenced by age. Our study shows that adiponectin is significantly and negatively associated with apoA-I FCR and that this association is independent of other factors usually associated with apoA-I FCR (sex, abdominal obesity, plasma triglycerides, HDL triglycerides, insulin sensitivity).…”

Section: Discussionsupporting

confidence: 60%

Adiponectin Is an Important Determinant of ApoA-I Catabolism

Vergès

Petit

Duvillard

et al. 2006

ATVB

125

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Objective-Plasma concentration of adiponectin is positively correlated with high-density lipoprotein (HDL) cholesterol level. However, the role of adiponectin on HDL metabolism remains unknown. This prompted us to perform an in vivo kinetic study of apoA-I, the main apolipoprotein of HDL, using stable isotopes, in 22 subjects with a wide range of plasma adiponectin, including 11 patients with metabolic syndrome (8 with type 2 diabetes, 3 without type 2 diabetes) and 11 normal individuals. Methods and Results-In the 22 studied subjects, plasma adiponectin levels ranged from 2.57 to 14.44 g/mL and apoA-I fractional catabolic rate (FCR) values ranged from 0.142 to 0.340 day Ϫ1 . A strong negative correlation was found between adiponectin and apoA-I FCR (rϭϪ0.66, PϽ0.001) in the whole studied population and, to a similar extent, in patients with metabolic syndrome (rϭϪ0.73, Pϭ0.010) and normal subjects (rϭϪ0.68, Pϭ0.020), separately. In multivariable analysis, apoA-I FCR was associated negatively with adiponectin (Pϭ0.005) and positively with HDL triglycerides/cholesterol ratio (Pϭ0.006), but not with age, sex, body mass index (BMI), waist circumference, plasma triglycerides, HDL cholesterol, fasting glycemia, and QUICKI. Both adiponectin and HDL triglycerides/cholesterol ratio explained 62% of the variance of apoA-I FCR and adiponectin on its own explained 43%. Conclusions-Our kinetic study shows a strong negative correlation between adiponectin and apoA-I FCR, which can explain the positive link between HDL cholesterol and adiponectin. This association is independent of obesity, insulin resistance, and the content of triglycerides within HDL particles. These data suggest that adiponectin may have a direct role on HDL catabolism. Key Words: adiponectin Ⅲ apoA-I Ⅲ HDL cholesterol Ⅲ insulin-resistance Ⅲ kinetic A diponectin is a peptide predominantly synthesized in the adipose tissue that plays an important role in carbohydrate and lipid metabolism and vascular biology. 1,2 It has been suggested to be a link between obesity, insulin resistance, and cardiovascular disease. Plasma adiponectin levels are reduced in individuals with abdominal obesity, metabolic syndrome, and/or type 2 diabetes. 1,3-5 Adiponectin concentration has been found negatively correlated with abdominal obesity and insulin resistance in humans 6,7 and has been shown to predict the development of type 2 diabetes. 8,9 Furthermore, several studies indicate that plasma adiponectin levels are significantly decreased in patients with coronary heart disease 10,11 and high plasma adiponectin predict a lower risk of future myocardial infarction in nondiabetic 12 and diabetic individuals. 13 However, the link between adiponectin and cardiovascular disease could be partly mediated by its effects on lipids, because several studies indicate that the inverse association between adiponectin and coronary disease is importantly attenuated or no more significant after adjustment for lipids, particularly high-density lipoprotein (HDL) cholesterol. 12,13 Adiponectin ...

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Section: Discussionsupporting

confidence: 60%

Adiponectin Is an Important Determinant of ApoA-I Catabolism

Vergès

Petit

Duvillard

et al. 2006

ATVB

125

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“…However, we do not think that this difference significantly modifies our results and conclusions. Indeed, HDL apoA-I kinetic does not seem to be modified by age according to data from the literature (47).…”

Section: Discussionmentioning

confidence: 86%

“…This absence of association between LDL changes and HDL-apoA-I production rate has been found in several kinetic studies. For instance, decrease in plasma LDL-cholesterol with atorvastatin is not associated with modification of apoA-I PR (29) Furthermore, the increase in plasma LDL-cholesterol level, observed after menopause or with saturated fat diet, is not coupled with any changes in apoA-I PR (46,47). Our results do not totally exclude that decrease in plasma LDLcholesterol level induced by rosuvastatin may have played a role in the increase in apoA-I PR, but this effect, if existing, is likely to be minor.…”

Section: Discussionmentioning

confidence: 99%

Rosuvastatin 20 mg restores normal HDL-apoA-I kinetics in type 2 diabetes

Vergès

Florentin

Baillot-Rudoni

et al. 2009

Journal of Lipid Research

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Catabolism of HDL particles is accelerated in type 2 diabetes, leading to a reduction in plasma residence time, which may be detrimental. Rosuvastatin is the most powerful statin to reduce LDL-cholesterol, but its effects on HDL metabolism in type 2 diabetes remain unknown. We performed a randomized double-blind cross-over trial of 6-week treatment period with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes. An in vivo kinetic study of HDL-apolipoprotein A-I (apoA-I) with 13 C leucine was performed at the end of each treatment period. Moreover, a similar kinetic study was carried out in eight nondiabetic normolipidemic controls. Rosuvastatin significantly reduced plasma LDL-cholesterol (251%), triglycerides (TGs) (238%), and HDL-TG (223%). HDL-apoA-I fractional catabolic rate (FCR) was decreased by rosuvastatin (0.25 6 0.06 vs. 0.32 6 0.07 pool/day, P 5 0.011), leading to an increase in plasma HDL-apoA-I residence time (4.21 6 1.02 vs. 3.30 6 0.73 day, P 5 0.011). Treatment with rosuvastatin was associated with a concomitant reduction of HDL-apoA-I production rate. The decrease in HDL-apoA-I FCR, induced by rosuvastatin, was correlated with the reduction of plasma TGs and HDL-TG. HDL apoA-I FCR and production rate values in diabetic patients on rosuvastatin were not different from those found in controls. Rosuvastatin is responsible for a 22% reduction of HDL-apoA-I FCR and restores to normal the increased HDL turnover observed in type 2 diabetes. These kinetic modifications may have beneficial effects by increasing HDL plasma residence time. Cardiovascular disease is the major cause of morbidity and mortality in patients with type 2 diabetes, and cardiovascular disease risk is 2-to 4-fold increased over nondiabetic subjects (1-4). Abnormalities of lipid metabolism, observed in type 2 diabetes, are one of the major factors contributing to vascular risk (5, 6). Diabetic dyslipidemia includes increased plasma triglycerides (TGs), decreased HDL-cholesterol levels, and qualitative lipoprotein abnormalities, such as TG enrichment of LDL and HDL particles (7, 8). Low HDL-cholesterol level, in patients with type 2 diabetes, has been shown to be due to increased catabolism of HDL lipoproteins by in vivo kinetic studies using radioisotopes (9) or stable isotopes (10). This increased catabolism of HDL particles leads automatically to significantly decrease their plasma residence time. The cardiovascular protective role of HDL is thought to be mainly due to its role in reverse cholesterol transport (11) and potentially to the antioxidative, anti-inflammatory, antithrombotic, and endothelium-dependent vasorelaxant effects of HDL particles (12). The increased catabolism of HDL lipoproteins is likely to reduce the cardioprotective effects of HDLs in patients with type 2 diabetes.Rosuvastatin is a statin that has been shown to reduce LDL-cholesterol more than the other statins at an equivalent dose (13). In addition, rosuvastatin significantly decreases plasma TG level with larger effect than prav...

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“…An age-related reduction in triglyceride levels has also been observed in male rabbits [16]. In contrast, in humans, aging is accompanied by increased levels of triglycerides, total cholesterol and non-HDL and decreased levels of HDL [17, 18]. Although there is no adequate evidence to explain the difference in changes of plasma lipid levels with age between humans and mice, the difference in the estrus cycle between these species may be an explanation.…”

Section: Discussionmentioning

confidence: 99%

Effect of Aging on Fatty Streak Formation in a Diet-Induced Mouse Model of Atherosclerosis

Li¹,

Gilbert²,

Matsumoto³

et al. 2007

J Vasc Res

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Age is considered to be a major risk factor for atherosclerosis, but it is unclear whether age has a direct effect on susceptibility to atherosclerosis. Wild-type mice develop fatty streak lesions in the aortic root only when fed a cholate-containing high fat/cholesterol diet. To investigate the influence of age on fatty streak formation, young (10 weeks) and old (53 weeks) female C57BL/6 mice were fed an atherogenic diet containing 15% fat, 1.25% cholesterol and 0.5% sodium cholate for 12 weeks. Atherosclerotic lesions at the aortic root were measured after cryosections were stained with oil red O. Results showed that old mice developed a comparable size of aortic lesions with young counterparts (5,600 ± 2,480 vs. 6,457 ± 1,537 µm²/section; p = 0.77), although old mice had significantly higher plasma cholesterol levels than young mice on the atherogenic diet (p < 0.05). Plasma levels of soluble vascular cell adhesion molecule 1 were significantly higher in old mice than in young mice on both chow and Western diets (p < 0.005). These data indicate that age has no direct effect on atherosclerosis susceptibility although it is accompanied by elevations in plasma cholesterol and vascular cell adhesion molecule 1 levels in C57BL/6 mice. Thus, increased cardiovascular events with age are probably related to a progressive increase in plaque size rather than to an increase in atherosclerosis susceptibility.

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TRL, IDL, and LDL Apolipoprotein B-100 and HDL Apolipoprotein A-I Kinetics as a Function of Age and Menopausal Status

Cited by 37 publications

References 54 publications

Adiponectin Is an Important Determinant of ApoA-I Catabolism

Adiponectin Is an Important Determinant of ApoA-I Catabolism

Rosuvastatin 20 mg restores normal HDL-apoA-I kinetics in type 2 diabetes

Effect of Aging on Fatty Streak Formation in a Diet-Induced Mouse Model of Atherosclerosis

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