A Pilot Study on Low-density Lipoprotein Receptor-related Protein-1 in Chinese Patients with Abdominal Aortic Aneurysm

Chan, Crystal Yin Tung; Chan, YH; Cheuk, B.L.Y.; Cheng, Swk

doi:10.1016/j.ejvs.2013.08.006

Cited by 22 publications

(30 citation statements)

References 39 publications

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“…In humans, LRP1 has been linked to the development of abdominal aortic aneurysms based on genetic associations and changes of LRP1 protein abundance in aneurysm tissue 11-13 . Therefore, it was predicted that SMC deletion of LRP1 would promote development of AAAs in normocholesterolemic mice during AngII infusion.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 A role for LRP1 in human AAAs has also been inferred by reduced abundance of LRP1 protein in aneurysmal tissue. 13 In addition to an implied role in AAAs, exome sequencing of LRP1 identified a missense mutation in patients with thoracic aortic aneurysms that are afflicted with Marfan syndrome. 14 These recent studies provide the basis for a potential role of LRP1 within aortic aneurysm formation.…”

Section: Introductionmentioning

confidence: 99%

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Smooth Muscle Cell Deletion of Low-Density Lipoprotein Receptor–Related Protein 1 Augments Angiotensin II–Induced Superior Mesenteric Arterial and Ascending Aortic Aneurysms

Davis

Rateri

Balakrishnan

et al. 2015

ATVB

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Objective LRP1, a multifunctional protein involved in endocytosis and cell signaling pathways, leads to a range of vascular pathologies when deleted in vascular smooth muscle cells (SMCs). The purpose of this study was to determine whether LRP1 deletion in SMCs influenced AngII-induced arterial pathologies. Approach and Results LRP1 protein abundance was equivalent in selected arterial-regions, but SMC-specific LRP1 depletion had no effect on abdominal and ascending aortic diameters in young mice. To determine the effects of LRP1 deficiency on AngII vascular responses, SMC-specific LRP1 (smLRP1) +/+ and -/- mice were infused with saline, AngII, or norepinephrine (NE). Several smLRP-/- mice died of superior mesenteric arterial (SMA) rupture during AngII infusion. In surviving mice, AngII profoundly augmented SMA dilation in smLRP1-/- mice. SMA dilation was blood pressure-dependent as demonstrated by a similar response during NE infusion. SMA dilation was also associated with profound macrophage accumulation, but minimal elastin fragmentation. AngII infusion led to no significant differences in abdominal aorta diameters between smLRP1+/+ and -/- mice. In contrast, ascending aortic dilation was exacerbated markedly in AngII-infused smLRP1-/- mice, but NE had no significant effect on either aortic region. Ascending aortas of smLRP1-/- mice infused with AngII had minimal macrophage accumulation but significantly increased elastin fragmentation and mRNA abundance of several LRP1 ligands including MMP-2 and uPA. Conclusions smLRP1 deficiency had no effect on AngII-induced abdominal aortic aneurysm formation. Conversely, AngII infusion in smLRP1-/- mice exacerbated SMA and ascending aorta dilation. Dilation in these two regions had differential association with blood pressure and divergent pathologic characteristics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Smooth Muscle Cell Deletion of Low-Density Lipoprotein Receptor–Related Protein 1 Augments Angiotensin II–Induced Superior Mesenteric Arterial and Ascending Aortic Aneurysms

Davis

Rateri

Balakrishnan

et al. 2015

ATVB

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“…LRP1 is also supposed to promote protective effect against aneurysm formation (reviewed by Strickland et al 2014). It was reported that LRP1 expression is decreased on the tissue of human abdominal aortic aneurysm (Chan et al 2013). The structure and function of the brain microvessels are likely to be different from large arteries including aortas, and the MV did not show obvious vascular abnormal changes in this study.…”

Section: Discussionmentioning

confidence: 73%

Immunohistochemical analysis of transporters related to clearance of amyloid-β peptides through blood–cerebrospinal fluid barrier in human brain

Matsumoto

Chiba

Fujihara

et al. 2015

Histochem Cell Biol

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A large number of previous reports have focused on the transport of amyloid-β peptides through cerebral endothelial cells via the blood-brain barrier, while fewer reports have mentioned the transport through the choroid plexus epithelium via the blood-cerebrospinal fluid barrier. Concrete roles of these two pathways remain to be clarified. In this study, we immunohistochemically examined the expression of transporters/receptors that are supposed to be related to the clearance of amyloid-β peptides in the choroid plexus epithelium, the ventricular ependymal cells and the brain microvessels, using seven autopsied human brains. In the choroid plexus epithelium, immunoreactivity for low-density lipoprotein receptor (LDLR), LDLR-related protein 1 (LRP1), LRP2, formylpeptide receptor-like 1 (FPRL1), ATP-binding cassette (ABC) transporter-A1 (ABCA1), ABCC1 and ABCG4 was seen in 7 of 7 brains, while that for ABCB1, ABCG2, RAGE and CD36 was seen in 0-2 brains. In the ventricular ependymal cells, immunoreactivity for CD36, LDLR, LRP1, LRP2, FPRL1, ABCA1, ABCC1 and ABCG4 was seen in 6-7 brains, while that for ABCB1, ABCG2 and RAGE was seen in 0-1 brain. Immunoreactivity for insulin-degrading enzyme (IDE) was seen in three and four brains in the choroid plexus epithelium and the ventricular ependymal cells, respectively. In addition, immunoreactivity for LDLR, ABCB1 and ABCG2 was seen in over 40 % of the microvessels (all seven brains), and that for FPRL1, ABCA1, ABCC1 and RAGE was seen in over 5 % of the microvessels (4-6 brains), while that for CD36, IDE, LRP1, LRP2 and ABCG4 was seen in less than 5 % of the microvessels (0-2 brains). These findings may suggest that these multiple transporters/receptors and IDE expressed on the choroid plexus epithelium, ventricular ependymal cells and brain microvessels complementarily or cooperatively contribute to the clearance of amyloid-β peptides from the brain.

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“…Low-density lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association with AAA size ( P = 0.0042) [58]. In a small pilot study in 12 patients by Chan et al [59], lipoprotein receptor-related protein 1 (LRP1) expression was found significantly lower in AAA patients than in controls, while no significant correlation was shown between LRP1 expression and the size of AAA ( P > 0.05). These results suggest that a reduction in LRP1 expression could be associated with aneurysm progression.…”

Section: Resultsmentioning

confidence: 99%

Novel Biomarkers of Abdominal Aortic Aneurysm Disease: Identifying Gaps and Dispelling Misperceptions

Moris

Mantonakis

Avgerinos

et al. 2014

BioMed Research International

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Abdominal aortic aneurysm (AAA) is a prevalent and potentially life-threatening disease. Early detection by screening programs and subsequent surveillance has been shown to be effective at reducing the risk of mortality due to aneurysm rupture. The aim of this review is to summarize the developments in the literature concerning the latest biomarkers (from 2008 to date) and their potential screening and therapeutic values. Our search included human studies in English and found numerous novel biomarkers under research, which were categorized in 6 groups. Most of these studies are either experimental or hampered by their low numbers of patients. We concluded that currently no specific laboratory markers allow screeing for the disease and monitoring its progression or the results of treatment. Further studies and studies in larger patient groups are required in order to validate biomarkers as cost-effective tools in the AAA disease.

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A Pilot Study on Low-density Lipoprotein Receptor-related Protein-1 in Chinese Patients with Abdominal Aortic Aneurysm

Abstract: Our pilot result suggests that a reduction in LRP1 protein expression may be associated with aneurysm progression.

Cited by 22 publications

References 39 publications

Smooth Muscle Cell Deletion of Low-Density Lipoprotein Receptor–Related Protein 1 Augments Angiotensin II–Induced Superior Mesenteric Arterial and Ascending Aortic Aneurysms

Smooth Muscle Cell Deletion of Low-Density Lipoprotein Receptor–Related Protein 1 Augments Angiotensin II–Induced Superior Mesenteric Arterial and Ascending Aortic Aneurysms

Immunohistochemical analysis of transporters related to clearance of amyloid-β peptides through blood–cerebrospinal fluid barrier in human brain

Novel Biomarkers of Abdominal Aortic Aneurysm Disease: Identifying Gaps and Dispelling Misperceptions

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