Effects of apolipoprotein M in uremic atherosclerosis

Bosteen, Markus H.; Svarrer, Eva Martha Madsen; Bisgaard, Line Stattau; Martinussen, Torben; Madsen, Marie; Nielsen, Lars Bo; Christoffersen, Christina; Pedersen, T.

doi:10.1016/j.atherosclerosis.2017.08.005

Cited by 16 publications

(9 citation statements)

References 35 publications

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“…ApoM-S1P has recently been proved to possess unique anti-inflammatory effects [18]. In this study, we discovered that ApoM-S1P exerts a crucial prestige on inflammatory response and pyroptosis of TNF-α induced HUVECs.…”

Section: Discussionmentioning

confidence: 70%

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Apolipoprotein M and sphingosine-1-phosphate complex alleviates TNF-α-induced endothelial cell injury and inflammation through PI3K/AKT signaling pathway

Liu

2019

BMC Cardiovasc Disord

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Background: In spite of the important role of Apolipoprotein-M (ApoM) and Sphingosine-1-Phosphate (S1P) played in atherosclerosis (AS), there was few related research reporting ApoM and S1P complex (ApoM-S1P) on biological activities of human umbilical vein endothelial cells (HUVECs). In this study, we explored the effect and mechanism of ApoM-S1P on TNF-α-induced inflammation in HUVECs.Methods: TNF-α was utilized to induce HUVEC injury and inflammation. After HUVECs were treated with antagonists of ApoM, S1P, ApoM + S1P, and ApoM + S1P + S1PR, calcein-acetoxymethyl ester was employed for the assessment of the adhesion of HUVECs to THP-1, immunofluorescence for the observation of caspase-1expression in HUVECs, reactive oxygen species (ROS) kit for the detection of ROS level in HUVECs. The impact of TNF-α, ApoM, S1P and S1PR antagonists on inflammatory response, pyroptosis and adhesion of THP-1 monocytes to HUVECs were determined by detecting expressions of pyroptosis related proteins (IL-1β, IL-18, ASC, NLRP3 and caspase-1), inflammatory cytokines (IL-6 and IL-10), adhesion molecules (E-selectin, ICAM-1, and VCAM-1) and p-PI3K/p-AKT by qRT-PCR and Western blot, as well as by ELISA. Results: TNF-α could increase adhesion of THP-1 monocytes to HUVECs and induce inflammatory response and pyroptosis in HUVECs, indicated by up-regulated expressions of E-selectin, ICAM-1, VCAM-1, IL-1β, IL-18, caspase-1, ASC, NLRP3, and IL-6, and down-regulated expression of IL-10. Co-treatment of ApoM-S1P on TNF-α treated HUVECs could protect HUVECs from injury and inflammation, evidenced by the attenuation of expressions of pyroptosis related proteins, inflammatory cytokines, and adhesion molecules, as well as the augment of PI3K and AKT phosphorylation. JTE-013, an antagonist of S1PR2, could reverse the amelioration of ApoM-S1P on pyroptosis and inflammation of HUVECs, indicating that ApoM-S1P could bind to S1PR2 to protect HUVECs from injury and inflammation through activating PI3K/AKT pathway.Conclusion: ApoM-S1P could attenuate TNF-α induced injury and inflammatory response in HUVECs by binding to S1PR2 to activate PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 70%

“…The implication of ApoM and S1P in AS has been evidenced in rodent models [17]. Nevertheless, the impact of ApoM-S1P complex (ApoM-S1P) in AS is presently controversial [18]. Data in recent study demonstrated that pyroptosis may be associated with AS by affecting the stability of atherosclerotic lesion [5].…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein M and sphingosine-1-phosphate complex alleviates TNF-α-induced endothelial cell injury and inflammation through PI3K/AKT signaling pathway

Liu

2019

BMC Cardiovasc Disord

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“…The incidence of cardiovascular disease in chronic kidney disease (CKD) patients is 80%, and the risk of death from cardiovascular events in hemodialysis patients is 10 to 20 times that of the general population [2]. The episode age of atherosclerosis is advanced, and vascular lesions progress faster in patients with end-stage renal disease, which is known as uremia accelerated atherosclerosis (UAAS), the age of onset is generally 30 to 40 [3]. As atherosclerosis is the main predictor of death of cardiovascular disease in hemodialysis patients, studies on occurrence and progression of atherosclerosis in uremic patients are of great significance for the prevention and treatment of cardiovascular diseases [4].…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of hydrogen sulfide against uremic accelerated atherosclerosis through cPKCβII/Akt signal pathway

Xiong

Song

et al. 2019

BMC Nephrol

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Background Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. The protection mechanism of hydrogen sulfide (H2S) and the specific role of conventional protein kinase C βII (cPKCβII)/Akt signaling pathway in the formation of atherosclerosis is still controversial. Methods 8-week-old male ApoE−/− mice were treated with 5/6 nephrectomy and high-fat diet to make uremia accelerated atherosclerosis (UAAS) model. Mice were divided into normal control group (control group), sham operation group (sham group), UAAS group, L-cysteine group (UAAS+L-cys group), sodium hydrosulfide group (UAAS+NaHS group), and propargylglycine group (UAAS+PPG group). Western blot was used to detect cPKCβII activation, Akt phosphorylation and endothelial nitric oxide synthase (eNOS) expression in mice aorta. Results The membrane translocation of cPKCβII in UAAS group was higher than sham group, and L-cys or NaHS injection could suppress the membrane translocation, but PPG treatment resulted in more membrane translocation of cPKCβII (P < 0.05, n = 6 per group). Akt phosphorylation and the eNOS expression in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation and the eNOS expression, but PPG treatment resulted in more decrease in the Akt phosphorylation and the eNOS expression (P < 0.05, n = 6 per group). Conclusion Endogenous cystathionine-γ-lyase (CSE)/H2S system protected against the formation of UAAS via cPKCβII/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule eNOS, which may be mediated by cPKCβII/Akt signaling pathway.

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“…Plasma cholesterol was measured in duplicate at baseline, midway, and at termination with the CHOD-PAP reagent (Roche Diagnostics). Fast protein liquid chromatography was performed on plasma pools, essentially as described previously, 23 with the following exception: plasma pools from all mice in each of the four treatment groups were made, and 400 mL of each pool was mixed with 400 mL phosphatebuffered saline before loading on the Superose 6 column (Amersham Pharmacia Biotech, Hørsholm, Denmark). Subsequently, cholesterol and triglyceride content was measured in the fast protein liquid chromatography fractions using standard enzymatic assays in an automated Cobas analyzer (Roche Diagnostics).…”

Section: Plasma Analysismentioning

confidence: 99%

Imiquimod-Induced Psoriasis-Like Skin Lesions Do Not Accelerate Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice

Madsen

Hansen

Nielsen

et al. 2018

The American Journal of Pathology

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Psoriasis is a chronic inflammatory skin disorder associated with several comorbidities, including atherosclerosis. Disease mechanisms that may affect both psoriasis and atherosclerosis include activation of T helper 1 and T helper 17 cells. Imiquimod application is an established mouse model of psoriasis-like skin inflammation. The cardiac glycoside digoxin inhibits the master transcription factor of T helper 17 differentiation, retinoid acid receptor-related orphan nuclear receptor γt, and attenuates IL-17-dependent pathologies in mice. We investigated whether cyclic imiquimod-induced psoriasis-like skin inflammation affects atherosclerosis in low-density lipoprotein receptor-deficient mice and whether digoxin modifies either disease. Topical imiquimod application increased ear thickness, keratinocyte proliferation, and accumulation of CD3 T cells in the skin of low-density lipoprotein receptor-deficient mice. Also, imiquimod affected the mice systemically with induction of splenomegaly as well as increased plasma levels of IL-17A and serum amyloid A. Overall, imiquimod reduced atherosclerosis in the aortic arch en face, but it did not affect atherosclerosis in the aortic root. Digoxin significantly reduced the imiquimod-induced ear thickening, had divergent effects on imiquimod-induced systemic inflammation, and did not affect atherosclerosis. In conclusion, cyclic imiquimod applications can be used for long-term induction of psoriasis-like skin lesions, but they attenuate atherosclerosis in low-density lipoprotein-deficient mice. In this model, digoxin reduces skin inflammation, but it has no effect on atherosclerosis.

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Effects of apolipoprotein M in uremic atherosclerosis

Cited by 16 publications

References 35 publications

Apolipoprotein M and sphingosine-1-phosphate complex alleviates TNF-α-induced endothelial cell injury and inflammation through PI3K/AKT signaling pathway

Apolipoprotein M and sphingosine-1-phosphate complex alleviates TNF-α-induced endothelial cell injury and inflammation through PI3K/AKT signaling pathway

Molecular mechanisms of hydrogen sulfide against uremic accelerated atherosclerosis through cPKCβII/Akt signal pathway

Imiquimod-Induced Psoriasis-Like Skin Lesions Do Not Accelerate Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice

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