Development of Nanoparticle Probes for In Vivo Imaging of Atherosclerotic Plaques

2012 ◽  
Author(s):  
Zihao Zhang ◽  
Sheng Tong ◽  
Gang Bao
Keyword(s):  
Surface Defects ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Necrotic Core ◽  
Intraplaque Hemorrhage ◽  
Atherosclerotic Plaques ◽  
Nanoparticle Probes ◽  
Arterial Lumen ◽  
Inflammatory Macrophage

Atherosclerosis, the formation of fatty plaques in the arterial lumen, is mediated by inflammatory macrophage infiltration in the lesion and ingestion of low-density lipoprotein (LDL), forming foam cells. Its progression will likely form a large necrotic core and fibrotic cap surface defects. The resulting intraplaque hemorrhage causes red blood cell infiltration and hemoglobin abundance, which oxidizes LDL to form cholesterol crystal aggregates (1). Hemorrhagic plaques could rupture and form artery-blocking emboli. Thus, it is critical to develop a tool to detect and locate unstable hemorrhagic plaques in live specimens.

In vivo and in vitro evidence for the glycoxidation of low density lipoprotein in human atherosclerotic plaques

2000 ◽  
Vol 150 (2) ◽  
pp. 343-355 ◽  
Author(s):  
Yoshinobu Imanaga ◽  
Noriyuki Sakata ◽  
Shigeo Takebayashi ◽  
Akira Matsunaga ◽  
Jun Sasaki ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Plaques ◽  
Low Density

Genistein inhibits the development of atherosclerosis via inhibiting NF-κB and VCAM-1 expression in LDLR knockout mice

2008 ◽  
Vol 86 (11) ◽  
pp. 777-784 ◽  
Author(s):  
Juejin Wang ◽  
Rongjian Zhang ◽  
Youhua Xu ◽  
Hong Zhou ◽  
Bin Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Knockout Mice ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Plaques ◽  
Sod Activity ◽  
Density Lipoprotein Receptor ◽  
Total Antioxidant ◽  
Antioxidative Ability

Diet can be an important factor that influences risks for cardiovascular disease. Genistein (4′,5,7-trihydroxyisoflavone), rich in soy, is one candidate that may benefit the cardiovascular system. Here, we explored the effect of genistein in atherosclerosis (AS) development in an in vivo mouse model. Low-density lipoprotein receptor (LDLR) knockout mice were allocated to control, model, and genistein groups. Our results showed that genistein significantly reduced the formation and development of atherosclerotic plaques ((4.68 ± 1.18) ×106 versus (6.65 ± 1.51) ×106 µm2, p < 0.05). In the genistein group, compared with the model group, total antioxidant capacity (TAC) level was 85.5 ± 15.6 versus 203.4 ± 32.6 mmol/L (p < 0.01); malondialdehyde (MDA) level was 3.79 ± 0.28 versus 3.06 ± 0.31 mmol/L (p < 0.01), and superoxide dismutase (SOD) activity was 86.1 ± 6.1 versus 139.1 ± 25.1 U/mL (p < 0.01). Therefore, genistein was able to enhance serum antioxidative ability in our mouse model. Genistein had no influence, however, on serum cholesterol and lipid profiles. Genistein also markedly downregulated the expression of nuclear factor (NF)-κB and vascular cell adhesion molecule (VCAM)-1 in aortas of mice (p < 0.05). These observations suggest that genistein may inhibit AS in LDLR−/− mice via enhancing serum antioxidation and downregulating NF-κB and VCAM-1 expression in the aorta.

scholarly journals The cellular biology of atherosclerosis with atherosclerotic lesion classification and biomarkers

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Leta Melaku ◽  
Addisu Dabi
Keyword(s):  
Atherosclerotic Plaque ◽  
Low Density Lipoprotein ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Plaque Formation ◽  
Necrotic Core ◽  
Atherosclerotic Plaques ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Lesion Classification

Abstract Background Atherosclerosis is a chronic lipid-driven inflammatory disease with infiltration of low-density lipoprotein and is considered as the pivotal step in plaque formation. The aim of the review is to get into the fine details of pathophysiologic mechanisms responsible for atherosclerosis with atherosclerotic lesion classification. It also provides a summary of current biomarkers other than the traditional risk factors so that new treatment modalities can emerge and reduce the morbidity and mortality associated with atherosclerosis. Main body In the classification of atherosclerosis made by American Heart Association (AHA), AHA Type I lesion is the earliest vascular change described microscopically. AHA Type II lesion is primarily composed of abundant macrophages. AHA Type III lesion is the earliest of progressive lesions, while AHA Type IV lesion consists of an acellular necrotic core. Various biomarkers are implicated in different stages of the pathophysiological mechanism of plaque formation and evolution. C Reactive Protein plays a direct role in promoting the inflammatory component of atherosclerosis. Fibrinogen was demonstrated to be elevated among patients with acute thrombosis. Higher leukocyte count is associated with a greater cardiovascular risk. Cytokines have been implicated in atheroma formation and complications. High rates of protease activated receptor expression are also induced by interleukin-6 secretion in atherosclerotic lesions and areas of vascular tissue injury. Cluster of differentiation 40 receptor and its ligand have been also detected in atherosclerotic plaques. Osteopontin, acidic phosphoprotein, and osteoprotegerin have emerged as novel markers of atherosclerotic plaque composition. There are also overproductions of matrix metalloproteinases in the rupture-prone regions and promote lipid-necrotic core formation in the atherosclerotic plaque. Myeloperoxidase has been proposed as a marker of plaque instability. Oxidized low-density lipoprotein receptor 1 provides a route of entry for oxidized low-density lipoprotein into the endothelium. A human atherosclerotic lesion also expresses lipoprotein-associated phospholipase A2. Short conclusion Atherosclerotic plaques are the battlefield between an unbalanced immune response and lipid accumulation in the intima of arteries. Most of the biomarkers associated with atherosclerosis are indicators of inflammatory response and will also be used for medical purposes.

scholarly journals Evaluation of [68Ga]Ga-DOTA-TCTP-1 for the Detection of Metalloproteinase 2/9 Expression in Mouse Atherosclerotic Plaques

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3168 ◽  
Author(s):  
Max Kiugel ◽  
Sanna Hellberg ◽  
Meeri Käkelä ◽  
Heidi Liljenbäck ◽  
Tiina Saanijoki ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Tracer Uptake ◽  
Atherosclerotic Plaques ◽  
Positron Emission ◽  
Pre Treatment ◽  
Targeting Peptide ◽  
Gallium 68

Background: The expression of matrix metalloproteinases 2/9 (MMP-2/9) has been implicated in arterial remodeling and inflammation in atherosclerosis. We evaluated a gallium-68 labeled peptide for the detection of MMP-2/9 in atherosclerotic mouse aorta. Methods: We studied sixteen low-density lipoprotein receptor deficient mice (LDLR-/-ApoB100/100) kept on a Western-type diet. Distribution of intravenously-injected MMP-2/9-targeting peptide, [68Ga]Ga-DOTA-TCTP-1, was studied by combined positron emission tomography (PET) and contrast-enhanced computed tomography (CT). At 60 min post-injection, aortas were cut into cryosections for autoradiography analysis of tracer uptake, histology, and immunohistochemistry. Zymography was used to assess MMP-2/9 activation and pre-treatment with MMP-2/9 inhibitor to assess the specificity of tracer uptake. Results: Tracer uptake was not visible by in vivo PET/CT in the atherosclerotic aorta, but ex vivo autoradiography revealed 1.8 ± 0.34 times higher tracer uptake in atherosclerotic plaques than in normal vessel wall (p = 0.0029). Tracer uptake in plaques correlated strongly with the quantity of Mac-3-positive macrophages (R = 0.91, p < 0.001), but weakly with MMP-9 staining (R = 0.40, p = 0.099). Zymography showed MMP-2 activation in the aorta, and pre-treatment with MMP-2/9 inhibitor decreased tracer uptake by 55% (p = 0.0020). Conclusions: The MMP-2/9-targeting [68Ga]Ga-DOTA-TCTP-1 shows specific uptake in inflamed atherosclerotic lesions; however, a low target-to-background ratio precluded in vivo vascular imaging. Our results suggest, that the affinity of gelatinase imaging probes should be steered towards activated MMP-2, to reduce the interference of circulating enzymes on the target visualization in vivo.

Oxidation of Plasma Low-Density Lipoprotein Accelerates Its Accumulation and Degradation in the Arterial Wall In Vivo

Circulation ◽  
1996 ◽  
Vol 94 (7) ◽  
pp. 1698-1704 ◽  
Author(s):  
Klaus Juul ◽  
Lars B. Nielsen ◽  
Klaus Munkholm ◽  
Steen Stender ◽  
Børge G. Nordestgaard
Keyword(s):  
Arterial Wall ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density

scholarly journals Interaction of 4-hydroxynonenal-modified low-density lipoproteins with the fibroblast apolipoprotein B/E receptor

1986 ◽  
Vol 234 (1) ◽  
pp. 245-248 ◽  
Author(s):  
W Jessup ◽  
G Jurgens ◽  
J Lang ◽  
H Esterbauer ◽  
R T Dean
Keyword(s):  
Apolipoprotein B ◽  
Negative Charge ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipid Peroxidation Product ◽  
Modified Low Density Lipoproteins ◽  
Peroxidation Product

The incorporation of the lipid peroxidation product 4-hydroxynonenal into low-density lipoprotein (LDL) increases the negative charge of the particle, and decreases its affinity for the fibroblast LDL receptor. It is suggested that this modification may occur in vivo, and might promote atherogenesis.

scholarly journals Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-).

1994 ◽  
Vol 35 (4) ◽  
pp. 669-677
Author(s):  
H.N. Hodis ◽  
D.M. Kramsch ◽  
P. Avogaro ◽  
G. Bittolo-Bon ◽  
G. Cazzolato ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein
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