Tolvaptan reduces angiotensin II-induced experimental abdominal aortic aneurysm and dissection

Tao Cheng Wu, Wei Hung Chang, Hsin Ying Lu, Chun Che Shih*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Tolvaptan has been approved for the treatment of autosomal dominant polycystic kidney disease and heart failure. However, the role of tolvaptan in patients with abdominal aortic aneurysm (AAA) has not been examined. Human aortic smooth muscle cells (HASMCs) were used as the in vitro model. Via Ang II infusion, experimental AAAs were induced in Apo-E knockout mice. In vitro study showed that tolvaptan suppressed matrix metalloproteinase (MMP) expressions (MMP-2 and MMP-9) and apoptosis in Ang II-stimulated HASMCs. In the Apo-E knockout mice with Ang II-induced AAA, the animals exhibited AAA formation with elastic lamina degradation, dilatation of the suprarenal aorta, increased macrophage infiltration and higher expressions of MMPs. Treatment with a high dose of tolvaptan prevented experimental AAA formation while preserving the elastic lamina structure, reducing inflammatory macrophages, and inhibiting gelatinolytic activity, MMP expressions and apoptosis of SMCs in aorta tissue. Specifically, tolvaptan reduced the expression of receptor-interacting protein kinase 3 (RIP3) and decreased apoptosis of SMCs. Our data demonstrated that tolvaptan reduces experimental AAA formation and dissection by inhibiting destruction of the aortic structure integrity and reducing inflammatory macrophage infiltration, MMP-2 and MMP-9 expressions, and apoptosis of vascular SMCs, indicating tolvaptan may have therapeutic potential for AAA and dissection.

Original languageEnglish
Article number106973
JournalVascular Pharmacology
Volume144
DOIs
StatePublished - Jun 2022

Keywords

  • Abdominal aortic aneurysm and dissection
  • Tolvaptan
  • Vasopressin type 2 antagonist

Fingerprint

Dive into the research topics of 'Tolvaptan reduces angiotensin II-induced experimental abdominal aortic aneurysm and dissection'. Together they form a unique fingerprint.

Cite this