LIPOPROTEIN REMNANTS AND ENDOTHELIAL DYSFUNCTION IN THE POSTPRANDIAL PHASE

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LIPOPROTEIN REMNANTS AND ENDOTHELIAL DYSFUNCTION IN THE POSTPRANDIAL PHASE

ABSTRACT

The objective of this work was to study whether changes in remnantlipoprotein(RLP)plasmalevelsduringthepostprandial phase relate to alterations of the endothelial function.

Fasted patients (15 moderately dyslipidemic men) were given an oral fat load (OFL), and blood samples were collected before the OFL ingestion (T0) and 2, 4, 6, and 8 h (T2, T4, T6, T8) thereafter. Endothelial function, determined as flowmediated dilatation (FMD) of the brachial artery, was assessed at the same time points.

Triglyceridemia peaked between T4 (5.48 0.64 mmol/liter) andT6(5.340.89mmol/liter)anddecreasedat8h(4.360.87 mmol/liter) after the OFL. FMD decreased significantly 6 h after the OFL consumption (from 16.03 1.32% to 11.53

THEROSCLEROSIS IS AN inflammatory disease involving the presence of both intra- and extracellular lipid deposits in arteries. More than 20 yr ago, Zilversmith (1) hypothesized that processes that occur during the postprandial phase are proatherogenic. Several clinical and experimental data suggest, in fact, that elevated postprandial lipemia is related to the presence of coronary artery disease (CAD) (2) and is an independent risk factor for coronary atherosclerosis (3). The role of the endothelium in the pathogenesis of cardiovascular diseases is well recognized (4). A close correlation exists between the presence of cardiovascular risk factors and a decrease of the endothelial vasodilator function (5). Endothelial function is reduced in patients with CAD (6, 7) or myocardial ischemia (8, 9). Furthermore, endothelial dysfunction predicts the recurrence of cardiovascular events (4, 10, 11) and progression of atherosclerotic disease (10).

The control of the main risk factors improves endothelial function. In fact, total cholesterol fasting levels (12, 13) are inversely related to the endothelial function; this condition is rapidly improved upon cholesterol reduction as best illustrated by the dramatic changes occurring after low-density lipoprotein (LDL) apheresis in familial hypercholesterolemia patients (14).

The endothelial function is transiently reduced in normo-

Abbreviations: Apo, Apolipoprotein; AUC, area under the curve; CAD, coronary artery disease; C-RLP, cholesterol remnant lipoprotein; FMD, flow-mediated dilation; LDL, low-density lipoprotein; OFL, oral fat load; RLP, remnant lipoprotein plasma; TG, triglyceride(s).

JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community.

1.42%, P < 0.01). Cholesterol in RLPs increased steadily up to 6 h and decreased at 8 h (T0 0.53 0.10, T6 0.81 0.11, T8 0.73 0.13 mmol/liter). Fasting levels of triglycerides and cholesterol-RLPs (C-RLPs) correlated significantly with FMD at baseline. The decrease in endothelial function at 6 h also significantly correlated with the area under the curve of triglycerides (R 0.53, P 0.04). Postprandial C-RLPs (area under the curve), however, showed the best correlation with the decrease of FMD (R 0.63, P 0.012). The correlation persisted in a multivariate analysis.

We concluded that C-RLPs contribute significantly to the endothelial dysfunction occurring during the postprandial lipemia. (J Clin Endocrinol Metab 89: 2946–2950, 2004)

cholesterolemic and hypercholesterolemic subjects during postprandial lipemia (15–18). The lipoprotein fraction(s) that may be involved in determining such an effect are unknown. Fasting remnant lipoprotein (RLP) plasma levels correlate directly with the endothelial dysfunction in peripheral (19) and coronary arteries (20), and changes in the postprandial phase correlate with the fasting endothelial function (21). Furthermore, RLP levels are strongly associated with angiographically verified progression of focal coronary atherosclerosis (22), and their lowering with gemfibrozil prevents vein graft stenosis (22). In addition, RLP levels are significantly increased after a fat loading (23).

This burden of evidence prompted us to investigate whether changes in RLP levels during the postprandial phase affect endothelial function.

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