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Updated: Feb 24, 2026
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Piezo1 aggravates diabetic vascular calcification by enhancing OGT-mediated RUNX2 O-GlcNAcylation in vascular smooth
Meijiang Chen1, Liuxiang Jiang1, Hui Yang2
1School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China; Key Laboratory of Clinical Pharmacology, Research Center of Medical Science, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, Guangdong Province, China.
Abstract:
Arterial calcification is the principal pathological marker of diabetic vascular complications. The principal causes of arterial calcification include hyperglycemia, advanced glycation end products (AGEs), and increased mechanical stress. Piezo1 is a mechanosensitive channel that is critically involved in vascular disease. The aim of this study is to clarify how Piezo1 activation promotes the calcification of cardiac smooth muscle cells through calcium-regulating mechanisms. In this study, the calcium-dependent regulatory mechanism of Piezo1 in a diabetic vascular calcification cell model was examined by using pharmacological and genetic approaches. Vascular smooth muscle-specific Piezo1 knockout mice were used to evaluate the protective function of Piezo1 in diabetic vascular calcification. In the diabetic mouse model, vascular calcification was associated with increased Piezo1 expression and enhanced O-GlcNAcylation. Piezo1 activation exacerbated calcification and O-GlcNAcylation in human coronary smooth muscle cells (HCASMCs), whereas Piezo1 inhibition alleviated these changes. Subsequent mechanistic studies revealed that Piezo1 interacts with Yes-associated protein 1 (YAP) and O-linked N-acetylglucosamine transferase (OGT) through calcium-dependent mechanisms, thereby enhancing the O-GlcNAcylation of runt-related transcription factor 2 (RUNX2) and promoting osteogenic development. Targeted Piezo1 ablation in smooth muscle reduced diabetes-related vascular calcification, increased vascular compliance, and restored regular molecular expression. This study demonstrated that Piezo1 augments OGT activity via a calcium-dependent YAP activation pathway, promoting the O-GlcNAcylation of Runx2, thereby advancing the osteogenic differentiation of HCASMCs and ultimately aggravating diabetic vascular calcification. Inhibiting the Piezo1 signaling pathway offers a novel approach for mitigating diabetic vascular complications.
Insights
Diabetic vascular complications involve arterial calcification. Piezo1 channel activation promotes this calcification via calcium signaling, O-GlcNAcylation, and Runx2 modification, offering a therapeutic target.
Area of Science:
- Cardiovascular Biology
- Molecular Mechanisms of Disease
- Diabetic Complications
Background:
- Arterial calcification is a key marker of diabetic vascular complications, driven by hyperglycemia, AGEs, and mechanical stress.
- Piezo1, a mechanosensitive channel, plays a role in vascular disease, but its specific role in diabetic arterial calcification is unclear.
Purpose of the Study:
- To elucidate the role of Piezo1 in promoting cardiac smooth muscle cell calcification through calcium-dependent pathways.
- To investigate the molecular mechanisms by which Piezo1 activation contributes to diabetic vascular calcification.
Main Methods:
- Utilized pharmacological and genetic approaches in a diabetic vascular calcification cell model using human coronary artery smooth muscle cells (HCASMCs).
- Employed vascular smooth muscle-specific Piezo1 knockout mice to assess Piezo1's protective function.
- Investigated protein interactions and post-translational modifications, including O-GlcNAcylation.
Main Results:
- Increased Piezo1 expression and O-GlcNAcylation were observed in diabetic mouse models with vascular calcification.
- Piezo1 activation in HCASMCs exacerbated calcification and O-GlcNAcylation, while inhibition alleviated these effects.
- Piezo1 was found to interact with YAP and OGT, enhancing O-GlcNAcylation of RUNX2 and promoting osteogenic differentiation.
Conclusions:
- Piezo1 activation promotes diabetic vascular calcification by augmenting OGT activity through a calcium-dependent YAP pathway, leading to Runx2 O-GlcNAcylation.
- Targeted Piezo1 ablation in smooth muscle reduced vascular calcification and improved vascular compliance in diabetic mice.
- Inhibiting the Piezo1 signaling pathway presents a potential therapeutic strategy for diabetic vascular complications.
