Developing a Strategy for Interventional Molecular Imaging of Oxidized Low-Density Lipoprotein in Atherosclerosis

Abstract

The identification of vulnerable coronary artery atherosclerotic plaques offers the prospect of either localized or systematic therapeutic targeting in order to prevent myocardial infarction. Molecular imaging of atherosclerosis adds to morphological imaging by focusing on the immunobiology hidden in and behind the endothelium and therefore may be able to improve the identification of prospective culprit lesions. Our focus has been on identifying arterial accumulation of oxidized low-density lipoprotein (oxLDL) by exploiting advances in knowledge of vascular pathobiology. Here, we reflect on our work developing near-infrared fluorescence imaging of oxLDL using LO1, a monoclonal autoantibody generated in our laboratory. We detail progress to date and discuss our vision on taking the work through the early translational pipeline toward a multitargeted approach in imaging rupture-prone atherosclerotic plaques. Ultimately, molecular imaging of coronary arteries should be able to assess the regional risk that is specific to a lesion, which can then be used in concert with global risk factors to personalize the therapeutic strategy for patients in a way that goes beyond generalized population-based therapies.

Vertebral artery hypoplasia as an independent risk factor of posterior circulation atherosclerosis and ischemic stroke

“…Atherosclerotic plaques were also located in areas where shear stress was less or more than normal, such as branches of the arteries, lateral wall of the bifurcations, and vascular curvatures. [ 19 – 21 ]…”

“…Physiological ESS values were demonstrated to be atheroprotective, and low or high values were atherogenic studies. Atherosclerotic plaques were also located in areas where shear stress was less or more than normal, such as branches of the arteries, lateral wall of the bifurcations, and vascular curvatures [19–21] …”

“…Atherosclerotic plaques were also located in areas where shear stress was less or more than normal, such as branches of the arteries, lateral wall of the bifurcations, and vascular curvatures. [19][20][21] The basilar artery originates from the confluence of the 2 vertebral arteries. Contrary to several systemic arteries, which have a tree-like branching pattern, the basilar artery is the only large artery in which 2 arterial flows unite.…”

Coronary Magnetic Resonance Angiography in Chronic Coronary Syndromes

“…It is also possible to directly target specific components of the atherosclerotic plaque (99)(100)(101). Various MR specific contrast agents are currently in development which can target molecular components that are involved in atherosclerotic plaque initiation, progression, instability and plaque rupture, such as elastin (102), tropoelastin, collagen (103,104), fibrin (105), and matrix metalloproteinases (106).…”