S100A12 Expression in Thoracic Aortic Aneurysm Is Associated With Increased Risk of Dissection and Perioperative Complications

Das, Deepanjana; Gawdzik, Joseph; Dellefave‐Castillo, Lisa; McNally, Elizabeth M.; Husain, Aliya N.; Raman, Jai; Bowman, Marion A. Hofmann

doi:10.1016/j.jacc.2012.04.027

Cited by 44 publications

(41 citation statements)

References 37 publications

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“…31 We identified significant increased expression of TLR6 in early RIAs (Figure 3), which mainly acts by forming heterodimers with TLR2, implying that this 31,32 suggest that increased expressions of S100/calgranulins are associated with severe and progressive subphenotypes of vascular diseases including IA.…”

Section: Strokementioning

confidence: 91%

Gene Expression Profiling Reveals Distinct Molecular Signatures Associated With the Rupture of Intracranial Aneurysm

Nakaoka

Tajima

Yoneyama

et al. 2014

Stroke

108

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Background and Purpose— The rupture of intracranial aneurysm (IA) causes subarachnoid hemorrhage associated with high morbidity and mortality. We compared gene expression profiles in aneurysmal domes between unruptured IAs and ruptured IAs (RIAs) to elucidate biological mechanisms predisposing to the rupture of IA. Methods— We determined gene expression levels of 8 RIAs, 5 unruptured IAs, and 10 superficial temporal arteries with the Agilent microarrays. To explore biological heterogeneity of IAs, we classified the samples into subgroups showing similar gene expression patterns, using clustering methods. Results— The clustering analysis identified 4 groups: superficial temporal arteries and unruptured IAs were aggregated into their own clusters, whereas RIAs segregated into 2 distinct subgroups (early and late RIAs). Comparing gene expression levels between early RIAs and unruptured IAs, we identified 430 upregulated and 617 downregulated genes in early RIAs. The upregulated genes were associated with inflammatory and immune responses and phagocytosis including S100/calgranulin genes ( S100A8 , S100A9 , and S100A12 ). The downregulated genes suggest mechanical weakness of aneurysm walls. The expressions of Krüppel-like family of transcription factors ( KLF2 , KLF12 , and KLF15 ), which were anti-inflammatory regulators, and CDKN2A , which was located on chromosome 9p21 that was the most consistently replicated locus in genome-wide association studies of IA, were also downregulated. Conclusions— We demonstrate that gene expression patterns of RIAs were different according to the age of patients. The results suggest that macrophage-mediated inflammation is a key biological pathway for IA rupture. The identified genes can be good candidates for molecular markers of rupture-prone IAs and therapeutic targets.

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Section: Strokementioning

confidence: 91%

Gene Expression Profiling Reveals Distinct Molecular Signatures Associated With the Rupture of Intracranial Aneurysm

Nakaoka

Tajima

Yoneyama

et al. 2014

Stroke

108

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“…54 Enhanced oxidative stress contributes to vascular calcification and S100A12, possibly via RAGE-driven ROS generation, may increase expression of osteoblastic genes that facilitate calcification. Moreover, S100A12 promotes apoptosis of aortic SMC, 61 and its expression may generate necrotic bodies, forming a nidus for calcification. 62 On the other hand, S100A12 is a potent inhibitor of matrix metalloproteases (MMP)-2 and -9, by virtue of its ability to chelate Zn 2+ from the active sites of these proteases.…”

Section: Calgranulins In Diseases Predisposing To Cardiovascular Riskmentioning

confidence: 99%

Calgranulins May Contribute Vascular Protection In Atherogenesis

Geczy

Chung

Hiroshima

2014

Circ J

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“…Indeed, the interaction of RAGE with its partner molecules has been reported to induce apoptosis in neurons, podocytes, tubular cells, and vascular smooth muscle cells (38)(39)(40). In addition, in a mouse model of heterotopic heart transplantation, inhibition of the RAGE axis by the administration of soluble RAGE (which competitively inhibits binding to membrane-bound RAGE) significantly impaired apoptosis in the graft and delayed the occurrence of rejection (41).…”

mentioning

confidence: 99%

Deletion of Receptor for Advanced Glycation End Products Exacerbates Lymphoproliferative Syndrome and Lupus Nephritis in B6-MRL Fas lpr/j Mice

Goury

Meghraoui-Kheddar

Belmokhtar

et al. 2015

The Journal of Immunology

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The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that interacts with advanced glycation end products, but also with C3a, CpG DNA oligonucleotides, and alarmin molecules such as HMGB1 to initiate a proinflammatory reaction. Systemic lupus erythematosus is an autoimmune disorder associated with the accumulation of RAGE ligands. We generated mice invalidated for RAGE in the lupus-prone B6-MRL Fas lpr/j background to determine the role of RAGE in the pathogenesis of systemic lupus erythematosus. We compared the phenotype of these mice with that of their wild-type and B6-MRL Fas lpr/j littermates. Lymphoproliferative syndrome, production of anti-dsDNA Abs, lupus nephritis, and accumulation of CD3+B220+CD4−CD8− autoreactive T cells (in the peripheral blood and the spleen) were significantly increased in B6-MRL Fas lpr/j RAGE−/− mice compared with B6-MRL Fas lpr/j mice (respectively p < 0.005, p < 0.05, p < 0.001, and p < 0.001). A large proportion of autoreactive T cells from B6-MRL Fas lpr/j mice expressed RAGE at their surface. Time course studies of annexin V expression revealed that autoreactive T cells in the spleen of B6-MRL Fas lpr/j-RAGE−/− mice exhibited a delay in apoptosis and expressed significantly less activated caspase 3 (39.5 ± 4.3%) than T cells in B6-MRL Fas lpr/j mice (65.5 ± 5.2%) or wild-type mice (75.3 ± 2.64%) (p = 0.02). We conclude that the deletion of RAGE in B6-MRL Fas lpr/j mice promotes the accumulation of autoreactive CD3+B220+CD4−CD8− T cells, therefore exacerbating lymphoproliferative syndrome, autoimmunity, and organ injury. This suggests that RAGE rescues the apoptosis of T lymphocytes when the death receptor Fas/CD95 is dysfunctional.

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S100A12 Expression in Thoracic Aortic Aneurysm Is Associated With Increased Risk of Dissection and Perioperative Complications

Cited by 44 publications

References 37 publications

Gene Expression Profiling Reveals Distinct Molecular Signatures Associated With the Rupture of Intracranial Aneurysm

Gene Expression Profiling Reveals Distinct Molecular Signatures Associated With the Rupture of Intracranial Aneurysm

Calgranulins May Contribute Vascular Protection In Atherogenesis

Deletion of Receptor for Advanced Glycation End Products Exacerbates Lymphoproliferative Syndrome and Lupus Nephritis in B6-MRL Fas lpr/j Mice

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