Identification of Circulating Endocan-1 and Ether Phospholipids as Biomarkers for Complications in Thalassemia Patients

Botta, Amy; Forest, Anik; Daneault, Caroline; Pantopoulos, Kostas; Tantiworawit, Adisak; Phrommintikul, Arintaya; Chattipakorn, Siriporn C.; Rosiers, Christine Des; Sweeney, Gary

doi:10.3390/metabo11020070

Cited by 3 publications

(3 citation statements)

References 73 publications

(103 reference statements)

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“…Botta et al found the endocan level to be high in transfusiondependent beta-thalassemia patients (beta-thalassemia major) 19 . This may be due to direct or indirect endothelial damage caused by chronic hemolysis and chronic iron overload in patients with β-thalassemia major.…”

Section: Discussionmentioning

confidence: 99%

Assessment of serum endocan levels in patients with beta-thalassemia minor

Khanmammadov

Zorlu

Özer

et al. 2022

Rev. Assoc. Med. Bras.

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OBJECTIVE: Beta-thalassemia minor is a blood disease caused by a hereditary decrease in beta-globin synthesis, frequently leading to hypochromic microcytic anemia. Formerly called endothelial cell-specific molecule 1, endocan is a proteoglycan released by vascular endothelial cells in many organs. Our aim was to investigate the relationship between the beta-thalassemia minor patients and the healthy control group in terms of serum endocan level. METHODS: The study was performed in a total of 80 subjects. They were divided into two groups, the beta-thalassemia minor group (n=40) and the healthy control group (n=40). Serum endocan levels, age, sex, body mass index value, and tobacco use data of these groups were compared. RESULTS: No statistically significant difference was detected between the two groups in terms of age, sex, and body mass index values (p>0.05). Endocan levels were measured to be 206.85±88.1 pg/mL in the beta-thalassemia minor group and 236.1±162.8 pg/mL in the control group with no significant difference between the groups in terms of serum endocan levels (p>0.05). CONCLUSIONS: In our study, there was no change in endocan level in beta-thalassemia minor. This might be because serum endocan levels are affected by multi-factorial reasons. Serum endocan levels may be altered secondarily to decreased beta-globin chain, increased sympathetic activity due to anemia, or platelet dysfunction induced by oxidative stress in beta-thalassemia minor. Further multicenter studies involving more patients are necessary to demonstrate this.

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Section: Discussionmentioning

confidence: 99%

Assessment of serum endocan levels in patients with beta-thalassemia minor

Khanmammadov

Zorlu

Özer

et al. 2022

Rev. Assoc. Med. Bras.

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“…A major perturbation in the plasma lipid profile was previously reported in thalassemia patients and three ether phospholipids were identified as potential biomarkers for thalassemic complications by our group via an untargeted lipidomics approach. 16 These data suggested that iron overload may disrupt lipid homeostasis. Here, we have employed the same untargeted lipidomics platform and unraveled a dysregulated lipid profile in the 20-week-old male Th3/+ mouse.…”

Section: Untargeted Lipidomicsmentioning

confidence: 99%

“…Untargeted lipidomics has been successfully applied to plasma from β‐thalassemia patients and revealed major perturbations, 16 indicating a potential role of different lipid subclasses in the development of cardiomyopathy. The role of the intestinal microbiota in dyslipidemia and cardiometabolic disease is well established 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Perturbations in lipid metabolism and gut microbiota composition precede cardiac dysfunction in a mouse model of thalassemia

Liu,

Fillebeen,

Forest

et al. 2023

The FASEB Journal

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Cardiomyopathy is a major complication of thalassemia, yet the precise underlying molecular mechanisms remain unclear. We examined whether altered lipid metabolism is an early driving factor in the development of cardiomyopathy using the Th3/+ mouse model of thalassemia. At age 20 weeks, male and female Th3/+ mice manifested anemia and iron overload; however, only males displayed metabolic defects and altered cardiac function. Untargeted lipidomics indicated that the circulating levels of 35 lipid species were significantly altered in Th3/+ mice compared to wild‐type controls: triglycerides (TGs) with saturated fatty acids (FAs; TG42:0 and TG44:0) were elevated, while TGs with unsaturated FAs (TG(18:2_20:5_18:2 and TG54:8)) were reduced. Similarly, phosphatidylcholines (PCs) with long chain FAs (palmitic (16:0) or oleic (18:1)) were increased, while PCs with polyunsaturated FAs decreased. Circulating PC(16:0_14:0), GlcCer(d18:1/24:0) correlated significantly with iron overload and cardiac hypertrophy. 16S rRNA gene profiling revealed alterations in the intestinal microbiota of Th3/+ mice. Differentially abundant bacterial genera correlated with PC(39:6), PC(18:1_22:6), GlcCer(d18:1/24:1) and CE(14:0). These results provide new knowledge on perturbations in lipid metabolism and the gut microbiota of Th3/+ mice and identify specific factors which may represent early biomarkers or therapeutic targets to prevent development of cardiomyopathy in β‐thalassemia.

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Discovery-Based Proteomics Identify Skeletal Muscle Mitochondrial Alterations as an Early Metabolic Defect in a Mouse Model of β-Thalassemia

Reboucas

Fillebeen

Botta

et al. 2023

IJMS

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Although metabolic complications are common in thalassemia patients, there is still an unmet need to better understand underlying mechanisms. We used unbiased global proteomics to reveal molecular differences between the th3/+ mouse model of thalassemia and wild-type control animals focusing on skeletal muscles at 8 weeks of age. Our data point toward a significantly impaired mitochondrial oxidative phosphorylation. Furthermore, we observed a shift from oxidative fibre types toward more glycolytic fibre types in these animals, which was further supported by larger fibre-type cross-sectional areas in the more oxidative type fibres (type I/type IIa/type IIax hybrid). We also observed an increase in capillary density in th3/+ mice, indicative of a compensatory response. Western blotting for mitochondrial oxidative phosphorylation complex proteins and PCR analysis of mitochondrial genes indicated reduced mitochondrial content in the skeletal muscle but not the hearts of th3/+ mice. The phenotypic manifestation of these alterations was a small but significant reduction in glucose handling capacity. Overall, this study identified many important alterations in the proteome of th3/+ mice, amongst which mitochondrial defects leading to skeletal muscle remodelling and metabolic dysfunction were paramount.

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Identification of Circulating Endocan-1 and Ether Phospholipids as Biomarkers for Complications in Thalassemia Patients

Cited by 3 publications

References 73 publications

Assessment of serum endocan levels in patients with beta-thalassemia minor

Assessment of serum endocan levels in patients with beta-thalassemia minor

Perturbations in lipid metabolism and gut microbiota composition precede cardiac dysfunction in a mouse model of thalassemia

Discovery-Based Proteomics Identify Skeletal Muscle Mitochondrial Alterations as an Early Metabolic Defect in a Mouse Model of β-Thalassemia

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