Atherosclerotic lesions targeted

In view of the detailed published information available on the presence, functional characteristics, and localization of scavenger receptor populations in atherosclerotic lesions (cf. above) as well as the known structural similarity between modified LDL and LCM (cf. Sections 12.1, 14.2.2-14.2.2(ii)), LCM-directed drug delivery to atherosclerotic lesions may offer a means for targeted drug-delivery therapy of atherosclerosis. 

Febbraio, M., Podrez, E., Smith, J., Hajjar, D., Hazen, S., Hoff, H., Sharma, K., and Silverstein. R. (2000) Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest 105, 1049-1056. 

The application of antibodies in cardiovascular targeting in vivo originated with the experimental demonstration of the feasibility of using radiolabeled antimyosin antibody for diagnosis of acute myocardial infarction in 1976. Since then, the use of antibodies in the cardiovascular system has encompassed imaging of myocarditis,heart transplant rejection, dilated cardiomyopathy, alcohol induced cardiomyopathy,adriamycin cardiotoxicity, various other cardiomyopathies, vascular clots, atherosclerotic lesions,and even certain cancers such as soft tissue sarcomas.f Yet the best characterized and studied antibody for cardiovascular diagnostic targeting is monoclonal antimyosin Fab for its exquisite specificity... 

Targeting Atherosclerotic Lesions with Radiolabeled Antibodies... 

Atherosclerosis is another intravascular pathological disorder that appears to be amenable to targeting with monoclonal antibodies. It was initially thought that atherosclerotic lesions possessed no unique compounds that could serve as specific targets. These lesions are... 

The recruitment of blood-borne cells to evolving atherosclerotic lesions appears to be specific for monocytes and requires the inducement of specific adhesion molecules on both the endothelial cell surface and the recruited monocytes. The adhesion process appears to be a multistep phenomenon. In the initial stages E- or P-selectin expressed by stimulated endothelial cells binds to carbohydrates borne by surface molecules on monocytes. Expression of P-selectin on vascular endothelial cells slows white blood cells and causes them to roll along the endothelial surface. Other cell adhesion molecules, including ICAM-1 and vascular cell adhesion molecule 1, then latch onto and stop the white blood cells completely, prior to their migration out of the blood vessel and into the target tissue. 

Park Y, Hong HY et al (2008) A new atherosclerotic lesion probe based on hydrophobically modified chitosan nanoparticles functionalized by the atherosclerotic plaque targeted peptides. J Control Release 128 217-223... 

Bursill et al. (2004) used adenoviral-mediated gene transfer to express a soluble broad spectrum CC-chemokine inhibitor, 35K, and they examined its efficacy in mediating atherosclerotic lesion formation. In mice expressing the soluble 35K inhibitor, atherosclerotic lesion size was reduced by 55%, and this was accompanied by an 85% decrease in macrophage recruitment. This report confirmed the involvement of CC chemokines in the initiation and progression of lesion development and demonstrated that broad-spectrum CC-chemokine inhibition is a rational therapeutic target. 

Laffitte BA, Joseph SB, Chen M, et al. The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions. Mol Cell Biol 2003 23 2182-2191. 

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