Academic Journal
Sex-mediated effects of transglutaminase 2 inhibition on endothelial function in human resistance arteries from diabetic and non-diabetic patients
| العنوان: | Sex-mediated effects of transglutaminase 2 inhibition on endothelial function in human resistance arteries from diabetic and non-diabetic patients |
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| المؤلفون: | Saii, Khatera, Prat-Duran, Judit, Simonsen, Ulf, Knudsen, Anders Riegels, Funder, Jonas Amstrup, Buus, Niels Henrik, Pinilla, Estefano |
| المصدر: | Saii , K , Prat-Duran , J , Simonsen , U , Knudsen , A R , Funder , J A , Buus , N H & Pinilla , E 2024 , ' Sex-mediated effects of transglutaminase 2 inhibition on endothelial function in human resistance arteries from diabetic and non-diabetic patients ' , Clinical Science . https://doi.org/10.1042/CS20242001 |
| سنة النشر: | 2024 |
| المجموعة: | Aarhus University: Research |
| الوصف: | Transglutaminase 2 (TG2) is an enzyme with multiple conformations. In its open conformation, TG2 exhibits transamidase activity linked to fibrosis, arterial remodeling, and endothelial dysfunction, a process enhanced by high glucose in endothelial cells. However, the closed conformation of TG2 contributes to transmembrane signaling and nitric oxide (NO)-dependent vasorelaxation. LDN 27219, a reversible allosteric inhibitor, stabilizes TG2 in its closed conformation. We examined whether pharmacological modulation of TG2 into its closed conformation induces vasorelaxation and enhances endothelium-dependent and independent relaxation in resistance arteries from age-matched diabetic (n=14) and non-diabetic patients (n=14) (age 71 (SEM: ±2). Subcutaneous arteries (diameter 133-1013 µm) were isolated from abdominal fat biopsies. TG2 mRNA expression and transamidase activity were assessed via RT-qPCR and 5-biotin(amido)pentylamine (5-BP) incorporation, while vascular reactivity was measured using wire myography. TG2 mRNA was highly expressed without significant differences between the groups and LDN 27219 induced concentration-dependent vasorelaxation in arteries from both groups. Sex-specific analysis revealed that potentiation of acetylcholine-induced vasorelaxation by LDN 27219 was driven by increased TG2 expression in non-diabetic females, while no effect was observed in arteries from non-diabetic males. Among diabetic patients, LDN 27219 increased maximal acetylcholine-induced vasorelaxation in males only. LDN 27219 did not affect endothelium-independent relaxation to sodium nitroprusside in either group. In conclusion, TG2 is expressed in human resistance arteries, and LDN 27219 induced vasorelaxation, selectively enhancing ACh relaxation in non-diabetic females, likely due to increased TG2 expression. This finding underscores the importance of sex differences in TG2 modulation of vasorelaxation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1042/CS20242001 |
| الاتاحة: | https://pure.au.dk/portal/en/publications/44c6737c-bf7a-4952-adc0-62327733166c https://doi.org/10.1042/CS20242001 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.18679636 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1042/CS20242001 |
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