Blocking endothelial adhesion molecules: a potential therapeutic strategy to combat atherogenesis.
OBJECTIVE
This review provides a concise update of the involvement of endothelial adhesion molecules in atherogenesis, an overview of current advances in the development of adhesion molecule blocking agents, as well as an insight into the potential of these molecules in cardiovascular therapy.


RESULTS
As endothelial adhesion molecules are deemed to play an important role in the development and progression of atherosclerotic lesions, they are interesting targets for therapeutic intervention in this process. In particular, P-selectin and vascular cell adhesion molecule 1 are widely considered to hold promise in this regard. Current research efforts centre on the design of agents that directly block the interaction of the receptor with its ligand (e.g. soluble P-selectin glycoprotein ligand 1, blocking antibodies, EWVD-based peptides) or that interfere with their synthesis (e.g. antisense oligonucleotides) or their regulatory control by nuclear factor kappa B or peroxisome proliferator-activated receptor gamma. Furthermore, adhesion molecules have been exploited as a target for the specific delivery of drug carriers (e.g. biodegradable particles with entrapped dexamethasone) or therapeutic compounds (e.g. dexamethasone) to the plaque. All approaches have been shown to be effective in blocking adhesion molecule function in in-vitro studies and in-vivo models for inflammation or atherosclerosis.


CONCLUSIONS
Although the field has achieved considerable progress in recent years, leading to the development of a number of interesting leads, final proof of their efficacy in cardiovascular therapy is eagerly awaited.
Lutters
Bianca C H
BC
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Leeuwenburgh
Michiel A
MA
Appeldoorn
Chantal C M
CC
Molenaar
Tom J M
TJ
Van Berkel
Theo J C
TJ
Biessen
Erik A L
EA
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology* / Q000628:therapy*; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D019087:Selectins
D007136:Immunoglobulins; D016023:Integrins; D019087:Selectins