2. Academic Validation
  3. TEA domain transcription factor 3 suppresses aortic and left ventricular remodeling via transcriptional activation of PDZ domain containing 1

TEA domain transcription factor 3 suppresses aortic and left ventricular remodeling via transcriptional activation of PDZ domain containing 1

  • Biochem Pharmacol. 2025 Sep 10;242(Pt 2):117329. doi: 10.1016/j.bcp.2025.117329.
Lei Wang 1,  Yufeng Bai 2,  Dan Ma 2,  Wenxiu Liu 2,  Zhiyu Shi 2,  Chunnan Liu 2,  Meng Zhao 2,  Huiying Wang 2,  Liying Luo 2,  Jinyu Chi 3
Affiliations

Affiliations

  • 1 Department of Medical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
  • 2 Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
  • 3 Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: 005959@hrbmu.edu.cn.
PMID: 40939874 DOI: 10.1016/j.bcp.2025.117329
Abstract

Hypertension is a risk factor for cardiovascular diseases, primarily through its induction of pathological vascular and ventricular remodeling. TEA domain transcription factor 3 (TEAD3) is a transcription factor highly expressed in myocardial tissues. PDZ domain-containing 1 (PDZK1) has been reported to protect blood vessels. This study discovered decreased expression of TEAD3 and PDZK1 in the aortic tissues of spontaneously hypertensive rats (SHRs). TEAD3 overexpression in SHR vascular smooth muscle cells (VSMCs) driven by the SM22α promoter was achieved through adeno-associated virus delivery. TEAD3 overexpression alleviated aortic remodeling by reducing elastic fiber and Collagen deposition. This improvement in vascular structure attenuated hypertension. Subsequently, ventricular remodeling was alleviated by reducing periaortic myocardial fibrosis and left ventricular posterior wall thickness. To elucidate the underlying mechanisms, we overexpressed TEAD3 or PDZK1 in SHR-derived VSMCs via adenoviral Infection. Both interventions suppressed VSMC proliferation and migration. Crucially, TEAD3 overexpression upregulated PDZK1 expression, and DNA pull-down assays confirmed direct binding of TEAD3 protein to the PDZK1 promoter. PDZK1 knockdown abolished the anti-proliferative and anti-migratory effects of TEAD3. Further analysis suggested that PDZK1 exerted its protective role by inhibiting the phosphoinositide-3-kinase adaptor protein 1-mediated PI3K/Akt pathway. In conclusion, this study reveals that TEAD3-PDZK1 axis attenuates the abnormal proliferation and migration of VSMCs, which ameliorates aortic and left ventricular remodeling in hypertensive conditions. These findings establish a molecular basis for developing targeted therapies against hypertension-induced cardiovascular remodeling.

Keywords

Hypertension; PDZ domain containing 1; TEA domain transcription factor 3; Vascular smooth muscle cell; Ventricular and vascular remodeling.

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