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American Heart Association

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Final ID: Tu0063

Smooth muscle cell-specific deletion of TXNIP ameliorates medial vascular calcification

Abstract Body: Vascular calcification is a significant pathological characteristic of cardiovascular diseases, often exacerbated by metabolic disorders such as chronic kidney disease and diabetes mellitus. Recent studies have highlighted oxidative stress and inflammation as central mechanisms in the development of vascular calcification. While TXNIP is known to positively regulate reactive oxygen species (ROS) generation and inflammasome activation, the specific contributions of TXNIP to vascular calcification have not been thoroughly elucidated. This study aimed to elucidate the role of TXNIP in the pathogenesis of vascular calcification through combined in vitro and in vivo approaches. Medial calcification was evaluated by murine models of a 5/6 nephrectomy mouse model and a vitamin D3-induced mouse model with nephropathy. In vivo results demonstrate that heightened TXNIP expression in vascular smooth muscle cells correlates with increased calcification. This association is evidenced by elevated calcium deposition, upregulation of osteogenic markers, and enhanced mitochondrial-derived ROS production. In contrast, targeted genetic modifications to induce TXNIP deficiency in smooth muscle cells significantly mitigate these effects. Moreover, suppression of TXNIP in these models inhibited inflammasome activation and mitochondrial dysfunction, suggesting a novel linkage between TXNIP activity and osteogenic differentiation pathways in medial calcification. The insights from this comprehensive study indicate that TXNIP not only amplifies oxidative stress and inflammation in vascular smooth muscle cells but also represents a potential therapeutic target for mitigating medial calcification. Modulating TXNIP expression or function may reduce the incidence of medial calcification in patients with cardiovascular diseases linked to metabolic disorders.
  • Hwang, Ae-rang  ( Yeungnam University College , Daegu , South Africa )
  • Author Disclosures:
    Ae-Rang Hwang: DO NOT have relevant financial relationships
Meeting Info:
Session Info:

01. Poster Session 1 & Reception

Tuesday, 04/22/2025 , 06:00PM - 08:00PM

Poster

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