2. Academic Validation
  3. The Piezo1/Extracellular Signal-Regulated Kinase Signal Pathway Regulates Proliferation and Migration of Aortic Vascular Smooth Muscle Cells and Participates in Thoracic Aortic Aneurysm

The Piezo1/Extracellular Signal-Regulated Kinase Signal Pathway Regulates Proliferation and Migration of Aortic Vascular Smooth Muscle Cells and Participates in Thoracic Aortic Aneurysm

  • Heart Lung Circ. 2025 Jul;34(7):704-718. doi: 10.1016/j.hlc.2025.03.012.
Weihong Nie 1,  Wenxuan Cao 2,  Yingzhu Zhuang 3,  Sumin Yang 4,  Hui Zhang 5,  Haoyu Hu 4,  Chunying Shi 6,  Hong Zhang 7
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China; Medical College, Qingdao University, Qingdao, Shandong Province, China.
  • 2 Department of Morphology, Qingdao Huanghai University, Qingdao, Shandong Province, China.
  • 3 Department of Heart Center, Qingdao Cardiovascular Disease Hospital, Qingdao, Shandong Province, China.
  • 4 Department of Cardiovascular Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • 5 Department of Organ Transplantation, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • 6 Medical College, Qingdao University, Qingdao, Shandong Province, China. Electronic address: cyshi@qdu.edu.cn.
  • 7 Department of Cardiovascular Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: zhhxw2666@163.com.
PMID: 40500623 DOI: 10.1016/j.hlc.2025.03.012
Abstract

Background: Vascular smooth muscle cell (VSMC) proliferation and migration contribute to vascular remodelling in thoracic aortic aneurysms (TAA). An increase in cytosolic CA2+ concentration triggers VSMC proliferation and migration. Piezo1, a mechanosensitive cation channel, may be involved in the proliferation and migration of VSMCs, and potentially in the development of TAA.

Method: This study analysed Piezo1 and its potential downstream protein extracellular signal-regulated kinases (ERK) in aortic surgical specimens from six patients with TAA and six controls. In in vitro experiments, Yoda1, a Piezo1 agonist, SCH772984, an ERK Inhibitor, si-Piezo1, used for silencing the piezo1 gene, and LM22B-10, an ERK Activator, were used to regulate the expression of Piezo1 and ERK in rat thoracic aortic VSMCs. The effects of these treatments on cell proliferation, migration, Apoptosis, and phenotypic switch were measured.

Results: Through the comparison of human samples, it was discovered that the expressions of Piezo1 and ERK in the aortic media of TAA were higher than in normal samples. Additionally, the levels of VSMC proliferation and Apoptosis were higher in TAA samples. This confirmed that upregulation of Piezo1 can induce cell proliferation and migration by activating the ERK pathway. It was also found that Piezo1/ERK signalling does not affect cell Apoptosis. Additionally, it was discovered that inhibiting Piezo1/ERK signalling can induce a phenotypical switch in cells.

Conclusions: These data indicate that Piezo1 is significantly activated in aortic VSMCs from patients with TAA, which may be involved in TAA by promoting VSMC proliferation and migration through the ERK signalling pathway. This study provides a new insight into the biological action of the Piezo1/ERK signalling pathway in the pathogenesis of TAA.

Keywords

Extracellular signal-regulated kinases; Migration; Piezo1; Proliferation; Thoracic aortic aneurysm; Vascular smooth muscle cells.

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