Journal of Clinical Pharmacy and Therapeutics

Volume 28, Issue 5 pp. 419-424

Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia

S. Marchesi MD,

S. Marchesi MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

G. Lupattelli MD,

G. Lupattelli MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

R. Lombardini BSc,

R. Lombardini BSc

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

A. R. Roscini MD,

A. R. Roscini MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

D. Siepi BSc,

D. Siepi BSc

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

G. Vaudo MD,

G. Vaudo MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

M. Pirro MD,

M. Pirro MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

H. Sinzinger MD,

H. Sinzinger MD

Department of Nuclear Medicine, University of Vienna, Austria

Search for more papers by this author

G. Schillaci MD,

G. Schillaci MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

E. Mannarino MD,

E. Mannarino MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

S. Marchesi MD,

S. Marchesi MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

G. Lupattelli MD,

G. Lupattelli MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

R. Lombardini BSc,

R. Lombardini BSc

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

A. R. Roscini MD,

A. R. Roscini MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

D. Siepi BSc,

D. Siepi BSc

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

G. Vaudo MD,

G. Vaudo MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

M. Pirro MD,

M. Pirro MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

H. Sinzinger MD,

H. Sinzinger MD

Department of Nuclear Medicine, University of Vienna, Austria

Search for more papers by this author

G. Schillaci MD,

G. Schillaci MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

E. Mannarino MD,

E. Mannarino MD

Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy

Search for more papers by this author

First published: 17 October 2003

https://doi.org/10.1046/j.0269-4727.2003.00512.x

Citations: 40

Simona Marchesi MD, Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Via Brunacci Brunamonti 51, 06122 Perugia, Italy. Tel.: +3907 557 83209; fax: +3907 557 36737; e-mail: [email protected]

Share a link

Email
Wechat
Bluesky

Summary

Background: Fasting and post-prandial hypertriglyceridemia have been associated with endothelial dysfunction.

Objective: To investigate the effects of a 3-month treatment with fenofibrate (200 mg daily) on endothelial reactivity and inflammatory state in hypertriglyceridemic patients at fast and after an oral fat load.

Methods: Brachial flow-mediated vasodilation (FMV) and the circulating levels of intercellular adhesion molecule (ICAM) and vascular cellular adhesion molecule (VCAM) were determined in 10 hypertriglyceridemic patients.

Results: Before treatment, post-prandial phase was characterized by an increase in triglycerides (3·7 ± 1 mmol/L at baseline vs. 4·2 ± 1, 6·5 ± 1, 6·6 ± 2, and 5·3 ± 2 mmol/L after 2, 4, 6, and 8 h), a decrease in FMV (4·3 ± 2% at baseline vs. 2·8 ± 1, 2·2 ± 1, and 1·3 ± 1% after 2, 4, and 6 h), and an increase in ICAM and VCAM. After fenofibrate there was a significant reduction in fasting triglycerides (3·7 ± 1·3 vs. 2·1 ± 0·8 mmol/L), ICAM (480 ± 113 vs. 269 ± 65 ng/mL) and VCAM (1821 ± 570 vs. 1104 ± 376 ng/mL), and an increase in FMV (4·3 ± 2 vs. 7·1 ± 2%). Post-prandially triglycerides increased (2·1 ± 1 at baseline vs. 2·4 ± 2 and 3·6 ± 1 mmol/L after 4 and 6 h), FMV decreased (7·1 ± 2 at baseline vs. 5·8 ± 2, 5·5 ± 2, 5·9 ± 2, 6·4 ± 2% after 2, 4, 6, and 8 h), and there was an increase of ICAM and VCAM. Before therapy post-prandial changes in FMV had an inverse correlation with the changes in triglycerides (r = −0·34; P < 0·05) and ICAM (r = −0·66; P < 0·001).

Conclusions: The transient endothelial dysfunction observed in hypertriglyceridemic subjects during post-prandial lipemia is mediated by post-prandial triglyceride increase and by the activation of inflammatory response. The anti-inflammatory activity of fenofibrate may represent an additional mechanism of its favorable action on the endothelial function during fasting and the post-prandial phase.

References

1 Austin MA, Hokanson JE, Edwards KL (1998) Hypertriglyceridemia as a cardiovascular risk factor. American Journal of Cardiology, 81, 7B–12B.
10.1016/S0002-9149(98)00031-9
CAS PubMed Web of Science® Google Scholar
2 Karpe F, Bard JM, Steiner G, Carlson LA, Fruchart JC, Hamsten A (1993) HDLs and alimentary lipemia. Studies in men with previous myocardial infarction at a young age. Arteriosclerosis and Thrombosis, 13, 11–22.
10.1161/01.ATV.13.1.11
CAS PubMed Web of Science® Google Scholar
3 Lupattelli G, Lombardini R, Schillaci G, Ciuffetti G, Marchesi S, Siepi D, Mannarino E (2000) Flow-mediated vasoactivity and circulating adhesion molecules in hypertriglyceridemia: association with small, dense LDL cholesterol particles. American Heart Journal, 140, 521–526.
10.1067/mhj.2000.108508
CAS PubMed Web of Science® Google Scholar
4 Lewis TV, Dart AM, Chin-Dusting JP (1999) Endothelium-dependent relaxation by acetylcholine is impaired in hypertriglyceridemic humans with normal levels of plasma LDL cholesterol. Journal of the American College of Cardiology, 33, 805–812
10.1016/S0735-1097(98)00667-6
CAS PubMed Web of Science® Google Scholar
5 Vogel RA, Corretti MC, Plotnick GD (1997) Effect of a single high-fat meal on endothelial function in healthy subjects. American Journal of Cardiology, 79, 350–354.
10.1016/S0002-9149(96)00760-6
PubMed Web of Science® Google Scholar
6 Marchesi S, Lupattelli G, Schillaci G, Pirro M, Siepi D, Roscini AR, Pasqualini L, Mannarino E (2000) Impaired flow-mediated vasoactivity during post-prandial phase in young healthy men. Atherosclerosis, 153, 397–402.
10.1016/S0021-9150(00)00415-9
CAS PubMed Web of Science® Google Scholar
7 De Caterina R, Basta G, Lazzerini G, Dell'Omo G, Petrucci R, Morale M, Carmassi F, Pedrinelli R (1997) Soluble vascular cell adhesion molecule-1 as a biohumoral correlate of atherosclerosis. Arteriosclerosis, Thrombosis and Vascular Biology, 17, 2646–2654.
10.1161/01.ATV.17.11.2646
CAS PubMed Web of Science® Google Scholar
8 Nappo F, Esposito K, Cioffi M, Giugliano G, Molinari AM, Paolisso G, Marfella R, Giugliano D (2002) Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals. Journal of the American College of Cardiology, 39, 1145–1150.
10.1016/S0735-1097(02)01741-2
CAS PubMed Web of Science® Google Scholar
9 Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC (1998) Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation, 98, 2088–2093.
10.1161/01.CIR.98.19.2088
CAS PubMed Web of Science® Google Scholar
10 Evans M, Anderson RA, Graham J et al. (2000) Ciprofibrate therapy improves endothelial function and reduces postprandial lipemia and oxidative stress in type 2 diabetes mellitus. Circulation, 101, 1773–1779.
10.1161/01.CIR.101.15.1773
CAS PubMed Web of Science® Google Scholar
11 Patsch JR, Miesenbock G, Hopferwieser T, Muhlberger V, Knapp E, Dunn JK, Gotto AM Jr, Patsch W (1992) Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb, 12, 1336–1345.
10.1161/01.ATV.12.11.1336
PubMed Web of Science® Google Scholar
12 Corretti MC, Anderson TJ, Benjamin EJ et al. (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. Journal of the American College of Cardiology, 39, 257–265.
10.1016/S0735-1097(01)01746-6
PubMed Web of Science® Google Scholar
13 Doi H, Kugiyama K, Ohgushi M et al. (1999) Membrane active lipids in remnant lipoproteins cause impairment of endothelium-dependent vasorelaxation. Arteriosclerosis, Thrombosis and Vascular Biology, 19, 1918–1924.
10.1161/01.ATV.19.8.1918
CAS PubMed Web of Science® Google Scholar
14 Drexler H, Zeiher AM, Wollschlager H, Meinertz T, Just H, Bonzel T (1989) Flow-dependent coronary artery dilatation in humans. Circulation, 80, 466–474.
10.1161/01.CIR.80.3.466
CAS PubMed Web of Science® Google Scholar
15 Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 288, 373–376.
10.1038/288373a0
CAS PubMed Web of Science® Google Scholar
16 Plotnick GD, Corretti MC, Vogel RA (1997) Effect of antioxidant vitamins on the transient impairment of endothelium-dependent brachial artery vasoactivity following a single high-fat meal. JAMA, 278, 1682–1686.
10.1001/jama.1997.03550200058032
CAS PubMed Web of Science® Google Scholar
17 Jonkers IJ, Mohrschladt MF, Westendorp RG, van der Laarse A, Smelt AH (2002) Severe hypertriglyceridemia with insulin resistance is associated with systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial. American Journal of Medicine, 112, 275–280.
10.1016/S0002-9343(01)01123-8
CAS PubMed Web of Science® Google Scholar
18 Doi H, Kugiyama K, Oka H, Sugiyama S, Ogata N, Koide SI, Nakamura SI, Yasue H (2000) Remnant lipoproteins induce proatherothrombogenic molecules in endothelial cells through a redox-sensitive mechanism. Circulation, 102, 670–676.
10.1161/01.CIR.102.6.670
CAS PubMed Web of Science® Google Scholar
19 Jang Y, Lincoff AM, Plow EF, Topol EJ (1994) Cell adhesion molecules in coronary artery disease. Journal of the American College of Cardiology, 24, 1591–1601.
10.1016/0735-1097(94)90162-7
CAS PubMed Web of Science® Google Scholar
20 Wallen NH, Held C, Rehnqvist N, Hjemdahl P (1999) Elevated serum intercellular adhesion molecule-1 and vascular adhesion molecule-1 among patients with stable angina pectoris who suffer cardiovascular death or non-fatal myocardial infarction. European Heart Journal, 20, 1039–1043.
10.1053/euhj.1999.1451
CAS PubMed Web of Science® Google Scholar
21 Simpson HS, Williamson CM, Olivecrona T et al. (1990) Postprandial lipemia, fenofibrate and coronary artery disease. Atherosclerosis, 85, 193–202.
10.1016/0021-9150(90)90111-U
CAS PubMed Web of Science® Google Scholar
22 Bae JH, Bassenge E, Lee HJ, Park KR, Park CG, Park KY, Lee MS, Schwemmer M (2001) Impact of postprandial hypertriglyceridemia on vascular responses in patients with coronary artery disease: effects of ACE inhibitors and fibrates. Atherosclerosis, 158, 165–171.
10.1016/S0021-9150(01)00408-7
CAS PubMed Web of Science® Google Scholar
23 Calabresi L, Gomaraschi M, Villa B, Omoboni L, Dmitrieff C, Franceschini G (2002) Elevated soluble cellular adhesion molecules in subjects with low HDL-cholesterol. Arteriosclerosis, Thrombosis and Vascular Biology, 22, 656–661.
10.1161/hq0402.105901
CAS PubMed Web of Science® Google Scholar
24 Neve BP, Fruchart JC, Staels B (2000) Role of the peroxisome proliferator-activated receptors (PPAR) in atherosclerosis. Biochemical Pharmacology, 60, 1245–1250.
10.1016/S0006-2952(00)00430-5
CAS PubMed Web of Science® Google Scholar
25 Delerive P, De Bosscher K, Besnard S et al. (1999) Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. Journal of Biological Chemistry 274, 32048–32054.
10.1074/jbc.274.45.32048
CAS PubMed Web of Science® Google Scholar

Citing Literature

All articles

Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia

Summary

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia

Summary

References

Citing Literature

References

Related

Information