Targeting Elastase for Molecular Imaging of Early Atherosclerotic Lesions

Abstract

This study provides evidence that elastase-targeted imaging can be used for in vivo detection of early atherosclerosis. This imaging approach may harbor potential in the clinical setting for earlier diagnosis and treatment of atherosclerosis.

Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis

“…Our findings are consistent with observations reported in various previous preclinical37, 38 and clinical7, 33, 34, 35, 36 studies that suggest an important role for NE in atherogenesis; however, these observations are disputed in another study. Soehnlein et al40 reported that mice lacking both NE and proteinase 3 displayed reduced atherosclerotic lesion size at early but not at advanced stages of lesion development, whereas lack of NE alone did not affect lesion formation.…”

“…Studies have also reported that elevated levels of plasma NE were observed in patients with various cardiovascular diseases,33, 34, 35, 36 and NE mRNA and protein were both detectable within human atherosclerotic plaques 7. More recent studies have reported increased plasma NE activity during atherosclerosis development37 and a reduction of atherosclerotic lesion in NE/proteinase 3 double knockout mice 38. Accordingly, NE has been suggested as a therapeutic target in atherosclerosis39 and could be used as a specific target for molecular imaging of early atherosclerotic lesions37; however, to date there has been no direct evidence indicating a causal role for NE in cardiovascular diseases.…”

“…More recent studies have reported increased plasma NE activity during atherosclerosis development37 and a reduction of atherosclerotic lesion in NE/proteinase 3 double knockout mice 38. Accordingly, NE has been suggested as a therapeutic target in atherosclerosis39 and could be used as a specific target for molecular imaging of early atherosclerotic lesions37; however, to date there has been no direct evidence indicating a causal role for NE in cardiovascular diseases. In the current study, we documented such a role for NE in atherosclerotic lesion formation.…”

120 Genetic and pharmacologic inhibition of the neutrophil elastase inhibits experimental atherosclerosis

“…7 More recent studies have reported increased plasma NE activity during atherosclerosis development 37 and a reduction of atherosclerotic lesion in NE/ proteinase 3 double knockout mice. 38 Accordingly, NE has been suggested as a therapeutic target in atherosclerosis 39 and could be used as a specific target for molecular imaging of early atherosclerotic lesions 37 ; however, to date there has been no direct evidence indicating a causal role for NE in cardiovascular diseases. In the current study, we documented such a role for NE in atherosclerotic lesion formation.…”

Paradigms in Fluorescence Molecular Imaging: Maximizing Measurement of Biological Changes in Disease, Therapeutic Efficacy, and Toxicology/Safety

“…Some publications in fluorescence inflammation imaging particularly stand out for their use of non-invasive fluorescence MI in challenging animal models and for their significant corroborating biology validation. For example, researchers have made extensive progress in using fluorescence tomography for detecting very early, non-invasive detection of cardiovascular disease by measuring macrophage protease activity, nanoparticle uptake, and/or integrin expression [38][39][40][41][42]. Pulmonary inflammation also presents challenges for non-invasive MI, due to imaging depth, heart interference, and complications of fluorescence imaging of air-filled tissue.…”