Key result
High-fat diet withdrawal reduces early MMP activation, correlating with reduced neointima after vascular injury.
Why the study?
Early noninvasive imaging methods to monitor matrix metalloproteinase activation for vascular remodeling progression and response to dietary modification were not established or validated.
Does withdrawal from a high-fat diet reduce MMP activation and vascular remodeling in ApoE-/- mice with carotid artery injury?
Does withdrawal from a high-fat diet reduce MMP activation and vascular remodeling in ApoE-/- mice with carotid artery injury?
Noninvasive imaging of MMP activation can track the amelioration of vascular remodeling following dietary modification in injured arteries.
May enable noninvasive MMP monitoring of vascular remodeling in mice; leaves open human translation and clinical adoption.
OBJECTIVE: To establish and validate early noninvasive imaging of matrix metalloproteinase (MMP) activation for monitoring the progression of vascular remodeling and response to dietary modification. METHODS AND RESULTS: Apolipoprotein E(-/-) mice that were fed a high-fat diet underwent left common carotid artery wire injury. One week after surgery, a group of animals were withdrawn from the high-fat diet. The other group of animals continued that diet throughout the study. Micro single-photon emission computed tomographic (microSPECT)/CT imaging with RP805 (a (99m)Tc-labeled tracer targeting activated MMPs) was repeatedly performed at 2 and 4 weeks after surgery. Histological analysis at 4 weeks showed significant left carotid neointima formation, monocyte/macrophage infiltration, and upregulation of several MMPs, which were ameliorated by withdrawal from the high-fat diet. In vivo microSPECT/CT images visualized significant RP805 uptake, reflecting MMP activation, in the injured carotid arteries. MMP activation was reduced as early as 1 week after withdrawal from the high-fat diet and significantly correlated with neointimal area at 4 weeks after surgery. CONCLUSIONS: MMP activation predicts the progression of vascular remodeling and can track the effect of dietary modification after vascular injury.
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Tavakoli et al. (2010) studied Vascular remodeling. Withdrawal from high-fat diet vs. Continued high-fat diet was evaluated on MMP activation (RP805 uptake) and neointima formation. Withdrawal from a high-fat diet reduced MMP activation as early as 1 week, which significantly correlated with neointimal area at 4 weeks after vascular injury.
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