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Carotid artery atherosclerosis: effect of intensive lipid therapy on the vasa vasorum--evaluation by using dynamic contrast-enhanced MR imaging.

ABSTRACT: To investigate whether short-term, intensive lipid therapy leads to changes in microvascular characteristics, as measured by using dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging.Institutional review board approval and informed consent were obtained for this HIPAA-compatible study. Subjects with established coronary artery disease or carotid artery stenosis of 15% or greater determined by using ultrasonography and with levels of apolipoprotein B of 120 mg/dL (1.2 g/L) or greater were enrolled in an ongoing study (clinical trial NCT00715273). All received intensive lipid therapy to achieve targeted high- and low-density lipoprotein cholesterol levels and underwent serial serum monitoring including high-sensitivity C-reactive protein (HsCRP) level measurements. Carotid artery MR imaging examinations including morphologic and DCE MR images were obtained at baseline and 1 year after treatment. In subjects with advanced lesions (>2 mm thick), MR image analysis was performed, including measurement of lipid-rich necrotic core size and kinetic modeling of DCE MR images to assess changes in the transfer constant (K(trans)). The differences in K(trans) between baseline and 1-year follow-up were compared by using the Wilcoxon signed rank test, and associations were assessed by using the Spearman rank correlation coefficient.Twenty-eight subjects with interpretable DCE MR imaging results at both baseline and 1-year follow-up were included. After 1 year of treatment, a significant reduction was found in mean K(trans) (0.085 min(-1) ± 0.037 [standard deviation] to 0.067 min(-1) ± 0.028, P = .02). Reduction in K(trans) was not significantly correlated with observed reductions in lipid-rich necrotic core size or reductions in HsCRP level.These findings suggest that DCE MR imaging may be a useful imaging method for the assessment of the therapeutic response of the vasa vasorum in patients with atherosclerotic plaque.

SUBMITTER: Dong L

PROVIDER: S-EPMC3121009 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Carotid artery atherosclerosis: effect of intensive lipid therapy on the vasa vasorum--evaluation by using dynamic contrast-enhanced MR imaging.

Dong Li L Kerwin Williams S WS Chen Huijun H Chu Baocheng B Underhill Hunter R HR Neradilek Moni Blazej MB Hatsukami Thomas S TS Yuan Chun C Zhao Xue-Qiao XQ

Radiology 20110414 1

<h4>Purpose</h4>To investigate whether short-term, intensive lipid therapy leads to changes in microvascular characteristics, as measured by using dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging.<h4>Materials and methods</h4>Institutional review board approval and informed consent were obtained for this HIPAA-compatible study. Subjects with established coronary artery disease or carotid artery stenosis of 15% or greater determined by using ultrasonography and with levels ...[more]

PMID: 21493792

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Project description:Expansion of the vasa vasorum network has been observed in a variety of systemic and pulmonary vascular diseases. We recently reported that a marked expansion of the vasa vasorum network occurs in the pulmonary artery adventitia of chronically hypoxic calves. Since hypoxia has been shown to stimulate ATP release from both vascular resident as well as circulatory blood cells, these studies were undertaken to determine if extracellular ATP exerts angiogenic effects on isolated vasa vasorum endothelial cells (VVEC) and/or if it augments the effects of other angiogenic factors (VEGF and basic FGF) known to be present in the hypoxic microenvironment. We found that extracellular ATP dramatically increases DNA synthesis, migration, and rearrangement into tube-like networks on Matrigel in VVEC, but not in pulmonary artery (MPAEC) or aortic (AOEC) endothelial cells obtained from the same animals. Extracellular ATP potentiated the effects of both VEGF and bFGF to stimulate DNA synthesis in VVEC but not in MPAEC and AOEC. Analysis of purine and pyrimidine nucleotides revealed that ATP, ADP and MeSADP were the most potent in stimulating mitogenic responses in VVEC, indicating the involvement of the family of P2Y1-like purinergic receptors. Using pharmacological inhibitors, Western blot analysis, and Phosphatidylinositol-3 kinase (PI3K) in vitro kinase assays, we found that PI3K/Akt/mTOR and ERK1/2 play a critical role in mediating the extracellular ATP-induced mitogenic and migratory responses in VVEC. However, PI3K/Akt and mTOR/p70S6K do not significantly contribute to extracellular ATP-induced tube formation on Matrigel. Our studies indicate that VVEC, isolated from the sites of active angiogenesis, exhibit distinct functional responses to ATP, compared to endothelial cells derived from large pulmonary or systemic vessels. Collectively, our data support the idea that extracellular ATP participates in the expansion of the vasa vasorum that can be observed in hypoxic conditions.

Dataset Information

Carotid artery atherosclerosis: effect of intensive lipid therapy on the vasa vasorum--evaluation by using dynamic contrast-enhanced MR imaging.

Publications

Carotid artery atherosclerosis: effect of intensive lipid therapy on the vasa vasorum--evaluation by using dynamic contrast-enhanced MR imaging.

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