Impaired high-density lipoprotein anti-oxidant capacity in human abdominal aortic aneurysm

Delbosc, Sandrine; Diallo, Djibril; Dejouvencel, Tiphaine; Lamiral, Zohra; Louedec, Liliane; Martin-Ventura, José Luis; Rossignol, Patrick; Lesèche, Guy; Michel, Jean‐Baptiste; Meilhac, Olivier

doi:10.1093/cvr/cvt194

Cited by 43 publications

(46 citation statements)

References 51 publications

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“…After intraluminal thrombus removal, the media (aneurysmal, n = 2, non-aneurysmal, n = 2) was separated from the adventitia following a dissection protocol routinely used in the laboratory. Our previous studies have repeatedly shown that we can obtain the medial and adventitial layers with minimal cross-contamination [23], [24]. Each layer was then cut into small pieces (1–2 mm 3 ) that were placed in enzyme mix [DMEM (Gibco) containing Dispase I (2.4 mg/mL, Roche), Collagenase P (0.6 mg/mL, Roche) and DNase I (Invitrogen, 0.3 mg/mL)] for adventitia and with also Elastase 0.1% (Worthington) for media pieces.…”

Section: Methodsmentioning

confidence: 90%

Deciphering the Stromal and Hematopoietic Cell Network of the Adventitia from Non-Aneurysmal and Aneurysmal Human Aorta

et al. 2014

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Aneurysm is associated to a complex remodeling of arteries that affects all their layers. Although events taking place in the intima and the media have received a particular attention, molecular and cellular events taking place in the adventitia have started to be deciphered only recently. In this study, we have precisely described the composition and distribution of stromal and hematopoietic cells in human arterial adventitia, both at steady state and in the setting of aortic aneurysm. Using polychromatic immunofluorescent and flow cytometry analyses, we observed that unlike the medial layer (which comprises mostly macrophages and T cells among leukocytes), the adventitia comprises a much greater variety of leukocytes. We observed an altered balance in macrophages subsets in favor of M2-like macrophages, an increased proliferation of macrophages, a greater number of all stromal cells in aneurysmal aortas. We also confirmed that in this pathological setting, adventitia comprised blood vessels and arterial tertiary lymphoid organs (ATLOs), which contained also M-DC8+ dendritic cells (slanDCs) that could participate in the induction of T-cell responses. Finally, we showed that lymphatic vessels can be detected in aneurysmal adventitia, the functionality of which will have to be evaluated in future studies. All together, these observations provide an integrative outlook of the stromal and hematopoietic cell network of the human adventitia both at steady state and in the context of aneurysm.

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Section: Methodsmentioning

confidence: 90%

Deciphering the Stromal and Hematopoietic Cell Network of the Adventitia from Non-Aneurysmal and Aneurysmal Human Aorta

et al. 2014

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“…This finding supports a potential mechanism whereby HDL bound A1AT may be involved in the preservation of vascular integrity, similar to the atherosclerosis scenario discussed above. Additionally, HDL isolated from these patients has impaired antioxidant activity (51). Total HDL and apoA-I levels have been demonstrated have a negative association with AAA occurrence and progression (52, 53).…”

Section: Potential Roles For Protease Regulation By Hdlmentioning

confidence: 99%

High density lipoproteins are modulators of protease activity: Implications in inflammation, complement activation, and atherothrombosis

Gordon

Remaley

2017

Atherosclerosis

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High density lipoproteins (HDL) represent a compositionally diverse population of particles in the circulation, containing a wide variety of lipids and proteins. Gene ontology functional analysis of the 96 commonly identified HDL binding proteins reveals that almost half of these proteins are either proteases or have known roles in protease regulation. Here, we discuss the activities of some of these proteins in regard to their roles in regulating proteases involved in inflammation, coagulation, and complement activation, particularly in the context of atherosclerosis. The overall goal of this review is to discuss potential functional roles of HDL in protease regulatory pathways based on current literature and known functions of HDL binding proteins and to promote the consideration of HDL as a global modulator of proteolytic equilibrium.

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“…Very recently, PRDX6 expression was shown to support higher Nox1-derived superoxide production, which was reduced by an inhibitor of PRDX6 phospholipase A2 activity36. The impaired antioxidant function reported in HDLs from AAA patients19 will likely be the result of the imbalance between the levels and activities of the various pro- and antioxidant proteins, including PRDX6.…”

Section: Discussionmentioning

confidence: 99%

“…The localization of PRDX6 in VSMCs of the AAA wall is probably a response to increased oxidative stress39, since PRDX6 expression in VSMCs is known to increase in response to H 2 0 2 40. Other oxidative stress markers identified in AAA tissue include the lipid peroxidation marker MDA and ceroids, which mark oxidation associated with lipids and RBCs19. We detected colocalization of PRDX6 with ceroids and MDA in the AAA thrombus; moreover, an intense PRDX6 signal was detected in cholesterol-rich and acellular atherosclerotic plaques in the AAA wall, colocalizing with MDA-positive areas.…”

Section: Discussionmentioning

confidence: 99%

“…These properties are attributable to HDL-associated proteins, and it is increasingly accepted that HDL composition, rather than quantity, is more important for its vasculo-protective activities. We previously demonstrated impaired anti-proteolytic18 and anti-oxidative functions19 in HDLs from human AAA. This effect has been linked to altered HDL protein composition or to impaired function of individual components.…”

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confidence: 97%

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Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

Burillo

Jorge

Martínez-López

et al. 2016

Sci Rep

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High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA.

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Impaired high-density lipoprotein anti-oxidant capacity in human abdominal aortic aneurysm

Cited by 43 publications

References 51 publications

Deciphering the Stromal and Hematopoietic Cell Network of the Adventitia from Non-Aneurysmal and Aneurysmal Human Aorta

Deciphering the Stromal and Hematopoietic Cell Network of the Adventitia from Non-Aneurysmal and Aneurysmal Human Aorta

High density lipoproteins are modulators of protease activity: Implications in inflammation, complement activation, and atherothrombosis

Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

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