Life-threatening bleeding from gastric mucosal angiokeratomas during anticoagulation

Kang, Eungu; Kim, Yoon-Myung; Kim, Dae–Hee; Yoo, Han-Wook; Lee, Beom Hee

doi:10.1097/md.0000000000006063

Cited by 3 publications

(1 citation statement)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Serpins are known to play a role in coagulation, and loss of serpins might induce a variety of bleeding disorders (Kaiserman et al, 2006 ). It has recently been shown that angiokeratoma, one of the first dermatologic disease presentations in Fabry patients, if present in gastrointestinal mucosa can lead to life-threatening bleeding episodes during coagulation therapy (Oh et al, 2016 ; Kang et al, 2017 ). Interestingly, 30% of Fabry patients show cerebral microbleeds (Kono et al, 2016 ), which together with the downregulated Thrombospondin 1 (Thsd7a) and Thromboxane a2 receptor (Tbxa2r) can be related to a general deficit in blood coagulation pathways.…”

Section: Discussionmentioning

confidence: 99%

Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model

Kummer

Kalpachidou

Kress

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Fabry disease is an X-linked lysosomal storage disorder with involvement of the nervous system. Accumulation of glycosphingolipids within peripheral nerves and/or dorsal root ganglia results in pain due to small-fiber neuropathy, which affects the majority of patients already in early childhood. The α-galactosidase A deficient mouse proved to be an adequate model for Fabry disease, as it shares many symptoms including altered temperature sensitivity and pain perception. To characterize the signatures of gene expression that might underlie Fabry disease-associated sensory deficits and pain, we performed one-color based hybridization microarray expression profiling of DRG explants from adult α-galactosidase A deficient mice and age-matched wildtype controls. Protein-protein interaction (PPI) and pathway analyses were performed for differentially regulated mRNAs. We found 812 differentially expressed genes between adult α-galactosidase A deficient mice and age-matched wildtype controls, 506 of them being upregulated, and 306 being downregulated. Among the enriched pathways and processes, the disease-specific pathways “lysosome” and “ceramide metabolic process” were identified, enhancing reliability of the current analysis. Novel pathways that we identified include “G-protein coupled receptor signaling” and “retrograde transport” for the upregulated genes. From the analysis of downregulated genes, immune-related pathways, autoimmune, and infection pathways emerged. The current analysis is the first to present a differential gene expression profile of DRGs from α-galactosidase A deficient mice, thereby providing knowledge on possible mechanisms underlying neuropathic pain related symptoms in Fabry patients. Therefore, the presented data provide new insights into the development of the pain phenotype and might lead to new treatment strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model

Kummer

Kalpachidou

Kress

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

Dabigatran-etexilate

2017

Reactions Weekly

View full text Add to dashboard Cite

Enhanced thrombospondin-1 causes dysfunction of vascular endothelial cells derived from Fabry disease-induced pluripotent stem cells

Park

et al. 2020

EBioMedicine

Self Cite

View full text Add to dashboard Cite

Background: Fabry disease (FD) is a recessive X-linked lysosomal storage disorder caused by a-galactosidase A (GLA) deficiency. Although the mechanism is unclear, GLA deficiency causes an accumulation of globotriaosylceramide (Gb3), leading to vasculopathy. Methods: To explore the relationship between the accumulation of Gb3 and vasculopathy, induced pluripotent stem cells generated from four Fabry patients (FD-iPSCs) were differentiated into vascular endothelial cells (VECs). Genome editing using CRISPR-Cas9 system was carried out to correct the GLA mutation or to delete Thrombospondin-1 (TSP-1). Global transcriptomes were compared between wild-type (WT)-and FD-VECs by RNA-sequencing analysis. Findings: Here, we report that overexpression of TSP-1 contributes to the dysfunction of VECs in FD. VECs originating from FD-iPSCs (FD-VECs) showed aberrant angiogenic functionality even upon treatment with recombinant a-galactosidase. Intriguingly, FD-VECs produced more p-SMAD2 and TSP-1 than WT-VECs. We also found elevated TSP-1 in the peritubular capillaries of renal tissues biopsied from FD patients. Inhibition of SMAD2 signaling or knock out of TSP-1 (TSP-1 À/À ) rescues normal vascular functionality in FD-VECs, like in gene-corrected FD-VECs. In addition, the enhanced oxygen consumption rate is reduced in TSP-1 À/À FD-VECs. Interpretation: The overexpression of TSP-1 secondary to Gb3 accumulation is primarily responsible for the observed FD-VEC dysfunction. Our findings implicate dysfunctional VEC angiogenesis in the peritubular capillaries in some of the complications of Fabry disease.

show abstract

Life-threatening bleeding from gastric mucosal angiokeratomas during anticoagulation

Cited by 3 publications

References 8 publications

Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model

Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model

Dabigatran-etexilate

Enhanced thrombospondin-1 causes dysfunction of vascular endothelial cells derived from Fabry disease-induced pluripotent stem cells

Contact Info

Product

Resources

About