Related Experiment Video
Updated: May 7, 2026
A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics
Published on: September 19, 2016
Vinpocetine alleviates the abdominal aortic aneurysm progression via VSMCs SIRT1-p21 signaling pathway
Hong-Qin Yang1,2, Zhi-Wei Li2, Xi-Xi Dong2
1Baotou Medical College, Baotou, 014040, Inner Mongolia Autonomous Region, China.
Abstract:
Abdominal aortic aneurysm (AAA) is a degenerative disease that caused mortality in people aged >65. Senescence plays a critical role in AAA pathogenesis. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. Our Previous study found cyclic nucleotide phosphodiesterase 1C (PDE1C) exacerbate AAA through aggravate vascular smooth muscle cells (VSMCs) senescence by downregulating Sirtuin1 (SIRT1) expression and activity. Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation, it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA. This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice. In addition, the elastin degradation, MMP (matrix metalloproteinase) activity, macrophage infiltration, ROS production, collagen fibers remodeling, and VSMCs senescence were decreased in AAA treated with vinpocetine. While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice. Accordingly, we revealed that vinpocetine suppressed migration, proliferation, and senescence in VSMCs. Moreover, vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy. In conclusion, this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.
Insights
Vinpocetine may treat abdominal aortic aneurysm (AAA) by reducing vascular smooth muscle cell (VSMC) senescence. This effect is dependent on Sirtuin1 (SIRT1), offering a potential new therapy for AAA.
Area of Science:
- Vascular Biology
- Aging Research
- Pharmacology
Background:
- Abdominal aortic aneurysm (AAA) is a significant cause of mortality, particularly in older adults.
- Cellular senescence in vascular smooth muscle cells (VSMCs) is a key factor in AAA development.
- Cyclic nucleotide phosphodiesterase 1C (PDE1C) exacerbates AAA by promoting VSMC senescence via Sirtuin1 (SIRT1) downregulation.
Purpose of the Study:
- To investigate if vinpocetine, a PDE1 inhibitor, can alleviate AAA by targeting the SIRT1 pathway.
- To determine the role of SIRT1 in vinpocetine's potential therapeutic effects on AAA.
Main Methods:
- Utilized an elastase-induced AAA mouse model.
- Administered vinpocetine pre-treatment to mice.
- Assessed aneurysmal dilation, aortic rupture, elastin degradation, matrix metalloproteinase (MMP) activity, macrophage infiltration, reactive oxygen species (ROS) production, collagen remodeling, and VSMC senescence.
- Examined effects in VSMC-specific SIRT1 knockout mice.
- Investigated vinpocetine's impact on VSMC migration, proliferation, and senescence, and its effect on SIRT1 degradation via autophagy.
Main Results:
- Vinpocetine pre-treatment significantly prevented aneurysmal dilation and reduced aortic rupture in AAA mice.
- Vinpocetine treatment decreased elastin degradation, MMP activity, macrophage infiltration, ROS production, collagen remodeling, and VSMC senescence.
- These protective effects were abolished in VSMC-specific SIRT1 knockout mice, highlighting SIRT1's crucial role.
- Vinpocetine inhibited VSMC migration, proliferation, and senescence.
- Vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy.
Conclusions:
- Vinpocetine demonstrates potential as a therapeutic agent for AAA.
- The therapeutic mechanism involves alleviating VSMC senescence through a SIRT1-dependent pathway.
- Vinpocetine's ability to inhibit SIRT1 degradation via autophagy is key to its protective effects in AAA.
More Related Videos
09:32Measurement of Pulse Propagation Velocity, Distensibility and Strain in an Abdominal Aortic Aneurysm Mouse Model
Published on: February 23, 2020
10:09Drug Treatment by Central Venous Catheter in a Mouse Model of Angiotensin II Induced Abdominal Aortic Aneurysm and Monitoring by 3D Ultrasound
Published on: August 4, 2022
Related Concept Videos
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:27Peripheral Artery Disease III: Interprofessional Care