Q J Med 2002; 95: 707-708
© 2002 Association of Physicians
Correspondence |
Reducing cholesterol and atherosclerosis: the importance of cellular adhesion molecules?
Department of General Practice & Primary Care, St George's Hospital Medical School, London
Sir,
We agree with the statement in the recent Editorial1 that even modest changes in LDL-cholesterol, using various lipid-lowering regimens, have significant effects on the incidence of clinical coronary events. We also agree that the improvement of cardiovascular end points is not fully explained by the reduction in LDL-cholesterol levels, and that statins may have other useful mechanisms of actions. Although it is mentioned that these include inflammatory responses and effects on plaque stability, there is no direct reference to the increasing evidence that suggests that statins have effects on the cellular adhesion molecule pathway. Cellular adhesion molecules may play an important role in the development of cardiovascular disease. However, the inconsistency of the results in some instances may be due to small sample sizes, differences in sample storage, selection, gender and/or ethnic group of participants.2
In a recent study, we looked at large numbers of male and female individuals from different ethnic backgrounds taken from a population study.3 There were significant gender differences in all of the adhesion molecules measured apart from Vascular Cellular Adhesion Molecule-1 (sVCAM-1). Furthermore, people of first-generation Black African origin living in England have significantly lower levels of Intracellular Cell Adhesion Molecule-1 (sICAM-1), sVCAM-1 and sP-selectin, but not sE-selectin, than Whites living in the same area.3 Moreover, associations with known risk factors are adhesion-molecule-specific. These factors clearly need to be taken into account in future studies along with sample size and patient selection, and results from one population cannot be readily extrapolated to other groups.2
The importance of serum lipids on the cellular adhesion molecule pathway is becoming increasingly apparent. Individuals with hypertriglyceridemia have higher levels of the sICAM-1 and sVCAM-1.4 HDL-cholesterol inhibits cytokine-induced expression of endothelial cell adhesion molecules. The oxidation of LDL can up-regulate the expression of adhesion molecules either directly, or indirectly, by amplifying the release of cytokines and oxidation of LDL enhances its uptake by monocytes.5–7 Moreover, in our study there were strong associations between serum lipids and adhesion molecule levels.3
Statins inhibit the synthesis of cholesterol, reduce cardiovascular morbidity and mortality and modulate several inflammatory mechanisms involved in the atherosclerotic processes.7 Atorvastatin treatment leads to a decrease in E-selectin levels8 and sP-Selectin, sICAM-1 and sE-Selectin levels are reduced following fluvastatin treatment.9 However, studies with pravastatin indicate that although it may not reduce adhesion molecule levels,10 it may be important in determining plaque stability rather than formation, as it increases the collagen content and decreases lipid content, inflammation, metalloproteinases and cell death in human carotid plaques.11 Thus different statins may have different actions.
Ethnic differences in serum lipid levels may influence the cellular adhesion pathways and provide a potential mechanism for the ethnic difference in CHD risk. Increased understanding of the underlying mechanisms and how their modification may vary in different individuals, particularly those of different ethnic origins, and how they may vary according to the drug used is therefore required to improve treatment regimens.
References
1. Hornung RS. Reducing cholesterol and atherosclerosis. Q J Med2002; 95:339–41.
2. Cappuccio FP, Miller MA. Soluble adhesion molecules and coronary heart disease. Lancet2002; 359:526–7.[Medline]
3. Miller MA, Sagnella GA, Kerry SM, Strazzullo P, Cappuccio FP. Ethnic differences in circulating soluble adhesion molecules. The Wandsworth Heart & Stroke Study 2002; submitted for publication.
4. Lupattelli G, Lombardini R, Schillaci G, et al. Flow-mediated vasoactivity and circulating adhesion molecules in hypertriglyceridemia: association with small, dense LDL cholesterol particles. Am Heart J2000; 140:521–6.[Web of Science][Medline]
5. Nofer JR, Kehrel B, Fobker M, Levkau B, Assmann G, Eckardstein A. HDL and arteriosclerosis: beyond reverse cholesterol transport. Atherosclersis2002; 161:1–16.
6. Blann AD, Lip GYP. Cell adhesion molecules in cardiovascular disease: what can soluble levels tell us? Heart1999; 81:101–2.
7. Case CC, Ballantyne CM. Statins and inflammatory markers. Curr Atheroscler Rep2002; 4:42–7.[Medline]
8. Hackman A, Abe Y, Insull W Jr, Pownall H, Smith L, Dunn K, Gotto AM Jr, Ballantyne CM. Levels of soluble cell adhesion molecules in patients with dyslipidemia. Circulation1996; 93:1334–8.
9. Van Haelst PL, Van Doormaal JJ, May JF, Gans ROB, Crijns HJGM, Cohen Tervaert JW. Secondary prevention with fluvastatin decreases levels of adhesion molecules, neopterin and C-reative protein. Eur J Int Med2001; 12:503–9.
10. Rauch U, Osende JI, Chesebro JH, Fuster V, Vorchheimer DA, Harris K, Harris P, Sandler DA, Fallon JT, Jayaraman S, Badimon JJ. Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins. Atherosclerosis2000; 153:181–9.[Web of Science][Medline]
11. Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation2001; 103:926–33.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||