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Lipid lowering and imaging protease activation in atherosclerosis.

ABSTRACT: Lipid lowering is a mainstay of modern therapeutic approach to atherosclerosis. We sought to evaluate matrix metalloproteinase (MMP)-targeted microSPECT imaging for tracking of the effect of lipid-lowering interventions on plaque biology in atherosclerotic mice in vivo.ApoE(-/-) mice fed on a high fat diet (HFD) for 2 months were randomly assigned to continuation of HFD, HFD plus simvastatin, HFD plus fenofibrate and high fat withdrawal (HFW). The animals underwent serial microSPECT/CT imaging using RP805, a (99m)Tc-labeled MMP-targeted tracer at 1 and 4 weeks after randomization. All three interventions reduced total blood cholesterol by 4 weeks. In animals on HFD, aortic arch RP805 uptake significantly increased from 1 week to 4 weeks. Tracer uptake in fenofibrate and HFW groups was significantly lower than uptake in the HFD group at 4 weeks. Similarly, CD 68 gene expression, reflecting plaque inflammation, was significantly lower in fenofibrate and HFW groups compared to HFD group. MMP tracer uptake significantly correlated with aortic CD68, but not VE-cadherin or smooth muscle ?-actin expression.MMP tracer uptake paralleled the effect of lipid-lowering interventions on plaque inflammation in atherosclerotic mice. MMP-targeted imaging may be used to track the effect of therapeutic interventions in atherosclerosis.

SUBMITTER: Razavian M

PROVIDER: S-EPMC3991560 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Lipid lowering and imaging protease activation in atherosclerosis.

Razavian Mahmoud M Nie Lei L Challa Azariyas A Zhang Jiasheng J Golestani Reza R Jung Jae-Joon JJ Robinson Simon S Sadeghi Mehran M MM

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 20131225 2

<h4>Background</h4>Lipid lowering is a mainstay of modern therapeutic approach to atherosclerosis. We sought to evaluate matrix metalloproteinase (MMP)-targeted microSPECT imaging for tracking of the effect of lipid-lowering interventions on plaque biology in atherosclerotic mice in vivo.<h4>Methods and results</h4>ApoE(-/-) mice fed on a high fat diet (HFD) for 2 months were randomly assigned to continuation of HFD, HFD plus simvastatin, HFD plus fenofibrate and high fat withdrawal (HFW). The a ...[more]

PMID: 24368425

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Project description:Atherosclerotic cardiovascular disease risk (ASCVD) is an ongoing epidemic, and lipid abnormalities are its primordial cause. Most individuals suffering a first ASCVD event are previously asymptomatic and often do not receive preventative therapies. The cornerstone of primary prevention has been the identification of individuals at risk through risk calculators based on clinical and laboratory traditional risk factors plus risk enhancers. However, it is well accepted that a clinical risk calculator misclassifies a significant proportion of individuals leading to the prescription of a lipid-lowering medication with very little yield or a missed opportunity for lipid-lowering agents with a potentially preventable event. The development of coronary artery calcium scoring (CAC) and CT coronary angiography (CCTA) provide complementary tools to directly visualize coronary plaque and other risk-modifying imaging components that can potentially provide individualized lipid management. Understanding patient selection for CAC or potentially CCTA and the risk implications of the different parameters provided, such as CAC score, coronary stenosis, plaque characteristics and burden, epicardial adipose tissue, and pericoronary adipose tissue, have grown more complex as technologies evolve. These parameters directly affect the shared decision with patients to start or withhold lipid-lowering therapies, to adjust statin intensity or LDL cholesterol goals. Emerging lipid lowering studies with non-invasive imaging as a guide to patient selection and treatment efficacy, plus the evolution of lipid lowering therapies from statins to a diverse armament of newer high-cost agents have pushed these two fields forward with a complex interaction. This review will discuss existing risk estimators, and non-invasive imaging techniques for subclinical coronary atherosclerosis, traditionally studied using CAC and more recently CCTA with qualitative and quantitative measurements. We will also explore the current data, gaps of knowledge and future directions on the use of these techniques in the risk-stratification and guidance of lipid management.

Dataset Information

Lipid lowering and imaging protease activation in atherosclerosis.

Publications

Lipid lowering and imaging protease activation in atherosclerosis.

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