Studies investigating RAGE expression in mouse models of atherosclerosis have used tissue extracts for protein analysis and quantitative immunohistochemistry [[4],[5]].
Surprisingly, in vivo studies performed in murine models of atherosclerosis suggested that CXCL16/SR-PSOX is atheroprotective, while its receptor CXCR6 is harmful.
After the encouraging results with the mouse models of atherosclerosis, we investigated whether 111In-DOTA-belatacept accumulates in human atherosclerotic plaques and whether the accumulation correlates with characteristics of plaque vulnerability.
Our work indicates that CX3CL1 and GM-CSF may represent putative biomarkers of inflammation associated with atherosclerosis, such as C-reactive protein, but are mechanistically tied to atherosclerosis based on the well established findings in animal models of atherosclerosis.
In both mouse models of atherosclerosis, LDL isolated from the plasma of mice on the n-6 polyunsaturated diet was rendered slightly more susceptible to oxidation in vitro, as indicated by a shorter lag period for diene formation.
Specifically, it discusses problems in translating findings from the most broadly used murine models of atherosclerosis into clinically feasible therapies and strategies potentially improving the results of clinical trials.
Studies of macrophage polarization in vitro and in mostly mouse models of atherosclerosis have led to a simplified view that M1 macrophages are facilitating the formation of the necrotic core and plaque destabilization, whereas M2 macrophages have anti-atherogenic properties mediating plaque stability [22].
Taken together, these results, the mechanistic findings in animal models of atherosclerosis, and our correlative findings between LDL cholesterol and CX3CL1 levels in humans, suggest that CX3CL1 may represent a biomarker of the inflammatory component of atherosclerosis and potentially define subjects at increased risk for atherosclerotic disease events.
We developed a radiolabeled monoclonal antibody fragment targeting a unique peptide sequence on the extracellular domain of the RAGE receptor and have shown in mouse models of atherosclerosis (apoE null) uptake on in vivo nuclear scans located in the sites of the atheroma in the aortic root and proximal aorta [[6],[7]].
Precise quantification of atherosclerotic plaque in preclinical models of atherosclerosis requires the volumetric assessment of the lesion(s) while maintaining in situ architecture.
In experimental models of atherosclerosis in mice, atorvastatin activates Smad signaling and increased collagen deposition in the atheroma plaques [12], [13].
