Other inducers of macrophage apoptosis have been investigated such as propamidine [96] and locally administered inhibitors such as cycloheximide for atherosclerosis treatment [95]. 4.3. Cardiovascular Disease The

role of monocytes/ macrophages #Selleckchem ROCK inhibitor randurls[1|1|,|CHEM1|]# in the development of atherosclerosis is undisputed [97, 98]. Following endothelial cell damage, monocytes are recruited to the site via the release of chemokines. Following extravasation to the intima, recruited and resident macrophages play a critical role in the Inhibitors,research,lifescience,medical development of the atherosclerotic plaque via the scavenging of oxidised LDL and the ultimate differentiation into foam cells which form the atheroscelotic plaque core. The glycoprotein CD36 is central to this process. CD36 is a member of the scavenger receptor class B which is expressed on macrophages/monocytes, platelets, and endothelial cells. Its importance in atherosclerosis has clearly been established through studies in the ApoE-deficient mice, Inhibitors,research,lifescience,medical demonstrating that inactivation of CD36 results in substantially reduced lesion size. Therefore targeting of CD36-expressing macrophages in atherosclerotic lesions using a ligand, for example, the growth peptide Hexarelin, can be envisaged

to have a dual effect—the delivery of therapeutic agents to the Inhibitors,research,lifescience,medical lesion and the neutralisation of LDL uptake. Hexarelin, a member of the hexapeptide growth Inhibitors,research,lifescience,medical hormone-releasing peptides (GHRPs), binds to CD36 receptors [99]. Investigations into liposome targeting to atherosclerotic lesions have looked at their potential for delivery of contrast agents for diagnostic imaging [100, 101] and anti-inflammatory drugs for therapy development. For instance, Chono and colleagues have investigated liposomal delivery to macrophages as a therapeutic approach to atherosclerosis in several studies [22, 40, 102] using anionic liposomes consisting of egg yolk phosphotidylcholine (PC), cholesterol, Inhibitors,research,lifescience,medical and DCP at a molar ratio 7:2:1 and sized to 70, 200 and 500nm. In vitro uptake by macrophages and foam cells was improved with increasing particle size [22, 40,

102]; however, in vivo, optimal aortic delivery in atherogenic mice was achieved using 200nm liposomes. In addition, various studies have shown significant antiatherosclerotic effects and in vivo by liposomal delivery of dexamethasone, cyclopentenone prostaglandins, and serum amyloid A (SAA) peptide fragments [22, 30, 103]. 4.4. Cerebral Ischemia and Stroke The role of the innate immune system and infiltrating macrophages and resident microglia in cerebral ischemia is currently an area of intense investigation. Inflammation, be it sterile or infection-induced, plays an important part in cerebral ischemic injury. Interestingly CD36 is upregulated in a number of inflammatory and pathological conditions, such as cerebral ischemia and stroke.