Related Experiment Video
Updated: Jun 29, 2026
Murine Surgical Model of Topical Elastase Induced Descending Thoracic Aortic Aneurysm
Published on: August 24, 2019
Stachydrine alleviates thoracic aortic aneurysm via regulating lactate dehydrogenase A in Marfan syndrome mice
Yufan Zhou1, Jiaqi Huang1, Hao Liu2
1Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan ,430022, China.
Background:
Marfan syndrome (MFS) is a genetic disorder predominantly caused by mutations in the FBN1 gene, leading to thoracic aortic aneurysm (TAA) and a lack of effective pharmacological treatments. However, the role of metabolic alterations in this process remains poorly understood.
Purpose:
We aim to investigate the regulatory roles of metabolites in MFS.
Methods:
Fbn1C1039G/+ mice were utilized as a TAA mouse model of MFS. Untargeted metabolomic screening of aortic tissues was conducted to identify metabolites in Fbn1C1039G/+ mice compared to controls. Echocardiographic and EVG staining were performed to evaluate TAA. Vascular smooth muscle cells (VSMCs) were isolated from mice for in vitro experiments. Proteomic sequencing was conducted to identify target mediators. Rescue experiments were carried out using recombinant LDHA in vitro.
Results:
Stachydrine (STA) was upregulated in Fbn1C1039G/+ mice aorta compared with controls. Administration of STA notably mitigated thoracic aortic dilation and medial degeneration in MFS mice. Furthermore, STA significantly diminished the elevated expression of matrix metalloproteinases and the excessive activation of the transforming growth factor-β (TGF-β) signaling pathway in vivo and in vitro. Proteomic analysis revealed that STA treatment led to a reduction in lactate dehydrogenase A (LDHA) expression. Rescue experiments further confirmed that LDHA acts as a critical mediator downstream of STA.
Conclusions:
STA attenuated TAA in MFS by inhibiting LDHA, thereby modulating TGF-β signaling and maintaining extracellular matrix homeostasis. These findings highlight STA as a protective metabolite and suggest LDHA as a potential therapeutic factor for TAA in MFS.
Insights
Stachydrine (STA) protects against thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) by inhibiting lactate dehydrogenase A (LDHA). This metabolite modulates TGF-β signaling, offering a potential therapeutic strategy for TAA.
Area of Science:
- Cardiovascular Biology
- Metabolomics
- Genetic Disorders
Background:
- Marfan syndrome (MFS) is a genetic disorder caused by FBN1 mutations, leading to thoracic aortic aneurysm (TAA) with limited treatment options.
- The role of metabolic dysregulation in MFS pathogenesis is not well understood.
Purpose of the Study:
- To investigate the regulatory functions of metabolites in Marfan syndrome.
- To identify potential therapeutic targets for thoracic aortic aneurysm in MFS.
Main Methods:
- Utilized Fbn1C1039G/+ mice as a model for MFS-induced TAA.
- Performed untargeted metabolomic screening on aortic tissues and proteomic sequencing on VSMCs.
- Conducted in vivo and in vitro experiments, including echocardiography, EVG staining, and rescue assays with LDHA.
Main Results:
- Stachydrine (STA) was found to be upregulated in MFS mouse aortas.
- STA administration significantly reduced thoracic aortic dilation, medial degeneration, and matrix metalloproteinase expression in MFS mice.
- STA treatment inhibited TGF-β signaling pathway activation and decreased lactate dehydrogenase A (LDHA) expression, with LDHA confirmed as a downstream mediator.
Conclusions:
- Stachydrine (STA) attenuates TAA in Marfan syndrome by inhibiting LDHA.
- STA modulates TGF-β signaling and maintains extracellular matrix homeostasis, highlighting its protective role.
- LDHA emerges as a potential therapeutic target for treating thoracic aortic aneurysm in MFS.
