Letter Regarding Article by Ferriera et al, “Postprandial Hypertriglyceridemia Increases Circulating Levels of Endothelial Cell Microparticles”
To the Editor:
We read with great interest the article by Ferriera et al1 reporting a significant elevation of circulating endothelial microparticles (EMPs) strictly correlated with postmeal increase in serum triglycerides in healthy normolipidemic subjects after a single high-fat meal. The results of the study add to the long list of previous research demonstrating impairment of endothelial functions after a single high-fat meal in otherwise healthy subjects. Some aspects of this work deserve further comment.
The authors’ statement about the calculated source of energy from fat (19%) in the high-fat meal is obviously wrong. Fifty grams of fat gives much more than 19% of energy if related to the total amount of the 900 energy units of the meal; a high-fat meal must contain at least 50% of energy from fat.
The authors do not address in full the issue of whether the release of EMP represents a cause or a consequence of endothelial dysfunction. In this context, we have shown that a single high-fat meal in healthy subjects produced endothelial activation as demonstrated by increased concentrations of soluble forms of the adhesion molecules ICAM-1 and VCAM-1.2 As the expression of numerous adhesion molecules is upregulated by proinflammatory cytokines,3 the parallel increase in circulating levels of tumor necrosis factor-α and interleukin-6 seen after a high-fat meal in our subjects may have induced endothelial activation. We have also shown a relationship between changes in serum triglycerides and changes in tumor necrosis factor-α (r=0.39, P<0.01) and VCAM-1 (r=0.25, P<0.05).
The authors do not disclose the mechanism whereby postprandial hypertriglyceridemia leads to increased levels of EMPs. In our study, pretreatment with antioxidant vitamin supplements normalized endothelial activation after the high-fat meal, suggesting that an oxidative mechanism mediated the effect of the high-fat meal on cytokine and adhesion molecule levels. This hypothesis was strengthened by the observation that another structurally unrelated antioxidant (eg, glutathione) prevents the increased ICAM-1 levels seen after postprandial hyperglycemia in humans.4 Thus, it would be interesting to know whether the increase in EMP levels after the high-fat meal is prevented by antioxidants.
Ferreira AC, Peter AA, Mendez AJ, Jimenez JJ, Mauro LM, Chirinos JA, Ghany R, Virani S, Garcia S, Horstman LL, Purow J, Jy W, Ahn YS, de Marchena E. Postprandial hypertriglyceridemia increases circulating levels of endothelial cell microparticles. Circulation. 2004; 110: 3599–3603.
De Caterina R, Liao JK, Libby P. Fatty acid modulation of endothelial activation. Am J Clin Nutr. 2000; 71: 213S–223S.
Ceriello A, Bortolotti N, Motz E, Crescentini A, Lizzio S, Russo A, Tonutti L, Toboga C. Meal-generated oxidative stress in type-2 diabetic patients. Diabetes Care. 1998; 21: 1529–1534.
We read with interest the comments of Guigliano and colleagues concerning our recent publication on postprandial elevation of endothelial microparticles (EMPs) after a high-fat meal.1 We apologize for our factual error about the percentage of energy units from fat in the protocol, which should read 45%.
They questioned whether the elevated EMPs represent a cause or consequence of the endothelial dysfunction. Our studies indicate that EMPs arise from endothelial cells (ECs) in response to activation or apoptosis.2 Thus, they are a result and not a cause of the endothelial dysfunction; however, cell-derived microparticles in the plasma of patients with acute coronary syndrome were shown to impair EC function.3 It remains to be seen whether postprandial EMPs are also toxic to ECs.
Guigliano et al have suggested that postprandial EC dysfunction may be mediated by cytokines, such as tumor necrosis factor-α or interleukin-6. We did not measure cytokines in our study, therefore, we cannot confirm their findings.4
EMPs are released from disturbed ECs and carry markers of the parent EC; they may also reflect the status of the EC. They are emerging as a promising marker of EC disturbances.2 Giugliano et al draw attention to their work showing a postprandial rise in soluble EC markers ICAM-1 and VCAM-1. We did not discuss the extensive literature on soluble markers of EC dysfunction in our article, but we recently reviewed them along with EMPs.2 These 2 forms arise by different mechanisms: EMPs rise by vesiculation and soluble markers by proteolysis. It is important to distinguish them because their sensitivity, specificity, and biological function may differ. So far, no systematic comparison between these 2 types of markers has been reported. We have found that “soluble” markers VCAM and ICAM are at least in part EMP bound.2
In summary, the observations of Giugliano et al are complementary to ours. The challenges facing EMP studies are (1) delineation of natural functions of EMPs, now believed to play a role as diffusible biomessengers carrying various signaling molecules that participate in atherosclerosis, thrombosis, and inflammation; and (2) clarification of which methodology, EMPs or soluble markers, is superior. It is likely that some combination of methods may provide maximum information on EC disturbances in health and disease.
The authors receive research support from the Wallace H. Coulter Foundation and funds from Mary Beth Weiss, Jane and Charles Bosco, and gifts from Frank Smather.
Ferreira AC, Peter AA, Mendez AJ, Jimenez JJ, Mauro LM, Chirinos JA, Ghany R, Virani S, Garcia S, Horstman LL, Purow J, Jy W, Ahn YS, de Marchena E. Postprandial hypertriglyceridema increases circulating levels of endothelial cell microparticles. Circulation. 2004; 110: 3599–3603.
Boulanger CM, Scoazec A, Ebrahimian T, Henry P, Mathieu E, Tedgui A, Mallat Z. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation. 2001; 104: 2649–2652.