Description of human AAA by cytokine and immune cell aberrations compared to risk-factor matched controls

Wang, S. Keisin; Green, Linden A.; Gutwein, Ashley R.; Drucker, Natalie A.; Motaganahalli, Raghu L.; Gupta, Alok; Fajardo, Andres; Murphy, Michael P.

doi:10.1016/j.surg.2018.03.002

Cited by 14 publications

(18 citation statements)

References 36 publications

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“…8A–E ). Inflammatory cytokines have been found to be highly correlated with AAA [ 1 , 23 , 25 , 26 ]. Since UC-MSCs have been known to play a vital role in the regulation of inflammatory reactions during aneurysm formation and progression, we further determined the protein level of TNF-α; results demonstrated a significantly lower protein level of TNF-α in UC-MSC-treated group compared with elastase group ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation

Wen

Wang

Gong

et al. 2020

Stem Cells and Development

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Abdominal aortic aneurysm (AAA) is life-threatening, for which efficient nonsurgical treatment strategy has not been available so far. Several previous studies investigating the therapeutic effect of mesenchymal stem cells (MSCs) in AAA indicated that MSCs could inhibit aneurysmal inflammatory responses and extracellular matrix destruction, and suppress aneurysm occurrence and expansion. Vascular smooth muscle cell (VSMC) phenotypic plasticity is reported to be predisposed in AAA initiation and progression. However, little is known about the effect of MSCs on VSMC phenotypic modulation in AAA. In this study, we investigate the therapeutic efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) in elastase-induced AAA model and evaluate the effect of UC-MSC on VSMC phenotypic regulation. We demonstrate that the intravenous injection of UC-MSC attenuates elastase-induced aneurysmal expansion, reduces elastin degradation and fragmentation, inhibits MMPs and TNFa expression, and preserves and/or restores VSMC contractile phenotype in AAA. Taken together, these results highlight the therapeutic and VSMC phenotypic modulation effects of UC-MSC in AAA progression, which further indicates the potential of applying UC-MSC as an alternative treatment candidate for AAA.

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Section: Resultsmentioning

confidence: 99%

“…Inflammatory cells and cytokines have been determined to be involved in the pathogenesis of AAA [ 25 , 46 ]. TNF-α is primarily produced by monocyte macrophage system in AAA [ 26 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation

Wen

Wang

Gong

et al. 2020

Stem Cells and Development

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“…Hence, melatonin ameliorated the reproductive damage caused by nicotine in the nicotine-related AAA model. Faulty immune regulation was also recently shown to contribute to aneurysm formation and growth (Wang et al, 2018b). The aorta wall loses its medial immune-privileged status, providing a permissive environment for immune cell infiltration and cytokine secretion, which may promote AAA (Cuffy et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm

Duan

Wang

et al. 2020

Front. Physiol.

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Smoking is a major risk factor for abdominal aortic aneurysm (AAA). Among the components of smoke, nicotine is known to exert pro-atherosclerotic, prothrombotic, and proangiogenic effects on vascular smooth muscle cells (VSMCs). The current study was designed to investigate the mechanisms through which nicotine induces vascular wall dysfunction and to examine whether melatonin protects against nicotine-related AAA. Methods: In this study, an enzyme-linked immunosorbent assay (ELISA) was used to measure melatonin and TNF-α levels, as well as total antioxidant status (TAS), in patients with AAA. We established a nicotine-related AAA model and explored the mechanisms underlying the therapeutic effects of melatonin. Tissue histopathology was used to assess vascular function, while western blotting (WB) and immunofluorescence staining were performed to detect protein expression. Results: We observed melatonin insufficiency in the serum from patients with AAA, particularly smokers. Moreover, melatonin level was positively correlated with antioxidant capacity. In the in vivo model, nicotine accelerated AAA expansion and destroyed vascular structure. Furthermore, OPN, LC3II, p62, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), NF-κB p65, TNF-α, phosphorylated AKT, and phosphorylated mTOR levels were increased, in vivo, following nicotine treatment, while SM22α and α-SMA levels were reduced. Additionally, melatonin attenuated the effects of nicotine on AAA and reversed changes in protein expression. Moreover, melatonin lost its protective effects following bafilomycin A1-mediated inhibition of autophagy. Conclusion: Based on our data, melatonin exerts a beneficial effect on rats with nicotine-related AAA by downregulating the AKT-mTOR signaling pathway, improving autophagy dysfunction, and restoring the VSMC phenotype.

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“…Lymphocytes may be both protective and pathogenic, and an imbalance between pro‐inflammatory and anti‐inflammatory lymphocytes may determine disease progression [8]. In accordance, lower blood levels of regulatory T cells and higher levels of inflammatory Th17 cells have been observed in individuals with asymptomatic AAA [17].…”

Section: Discussionmentioning

confidence: 99%

Leukocyte subsets and abdominal aortic aneurysms detected by screening in men

et al. 2020

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Objective In the present case–control study, we describe the associations between leukocyte subsets in blood and early, screening‐detected AAA in men. An abdominal aortic aneurysm (AAA) may result in a life‐threatening rupture of the aortic wall. The trigger for AAA formation remains unknown, but the vascular adventitia of advanced AAAs is infiltrated by various leukocytes, indicating that the pathogenesis may involve inflammation. Methods In Sweden, all 65‐year‐old men are invited to an ultrasound examination for detection of AAA. At the Gothenburg screening site, 16 256 men were examined in 2013–2017, 1.2% of whom had an AAA (diameter of the infrarenal aorta ≥30 mm). All men with AAA at screening as well as a randomized selection of AAA‐free screened men were invited to participate in a case–control study. Results The median diameter of AAAs was 33 mm. Men with an AAA (n = 151) had a higher frequency of smoking, hypertension and statin use than controls (n = 224). Blood levels of neutrophils, lymphocytes, monocytes and basophils were higher in individuals with an AAA, but eosinophil count did not differ from controls. Odds ratios (95% confidence interval) for AAA were 8.6 (4.2–17.4), 3.5 (1.9–6.6) and 3.3 (1.8–6.3) for the highest versus lowest quartile of neutrophils, lymphocytes and monocytes, respectively. For neutrophils and lymphocytes, the association with AAA remained significant after adjustment for smoking and other known risk factors/markers. Conclusion Several, but not all, subsets of circulating leukocytes are associated with screening‐detected AAA in men, which is insufficiently explained by associations with smoking and other confounders.

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Description of human AAA by cytokine and immune cell aberrations compared to risk-factor matched controls

Abstract: In this investigation, we systematically characterize the abdominal aortic aneurysm-immune environment and present preliminary evidence that faulty immune regulation may also contribute to aneurysm formation and growth.

Cited by 14 publications

References 36 publications

Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation

Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation

Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm

Leukocyte subsets and abdominal aortic aneurysms detected by screening in men

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