Related Experiment Video
Updated: Jun 18, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Lanatoside C, a Novel Senolytic, Ameliorates Atherosclerosis in Mice
Eok-Cheon Kim1,2, Youlim Son1,2, Seon-Hui Kim1,2
1Department of Biochemistry and Molecular Biology, Daegu 42415, Republic of Korea.
Abstract:
Cellular senescence, a state of irreversible cell cycle arrest, contributes to aging and age-related diseases. Senolytics targeting cellular senescence could be applied to the prevention and treatment of age-related diseases. In this study, we identified lanatoside C (Lana C) as a senolytic compound. Lana C, a cardiac glycoside used for the treatment of cardiovascular diseases, is known to inhibit the transmembrane protein sodium-potassium adenosine triphosphatase (Na+/K+-ATPase). We found that Lana C depolarized and acidified senescent human umbilical vein endothelial cells (HUVECs), making them susceptible to apoptosis. The senolytic activity of Lana C was inhibited by potassium chloride (KCl) and Z-VAD-FMK (ZVF), a widely used pan-caspase inhibitor. Additionally, Lana C significantly ameliorated the senescence burden and the formation of atherosclerotic lesions in apolipoprotein E (ApoE-/-) or low-density lipoprotein receptor (Ldlr-/-) knockout mice. These results suggest that Lana C could be a promising senolytic for age-related diseases.
Insights
Lanatoside C (Lana C) is a novel senolytic compound that eliminates senescent cells, potentially preventing age-related diseases. This cardiac glycoside shows promise in reducing aging markers and atherosclerotic lesions in mice.
Area of Science:
- Gerontology
- Cardiovascular Research
- Cell Biology
Background:
- Cellular senescence, a state of irreversible cell cycle arrest, is a key driver of aging and associated diseases.
- Senolytic therapies aim to clear senescent cells for disease prevention and treatment.
Purpose of the Study:
- To identify and characterize novel senolytic compounds for age-related diseases.
- To investigate the senolytic potential of lanatoside C (Lana C).
Main Methods:
- Lanatoside C (Lana C) was tested for senolytic activity on senescent human umbilical vein endothelial cells (HUVECs).
- Mechanisms of action were explored using potassium chloride (KCl) and Z-VAD-FMK (ZVF).
- In vivo efficacy was assessed in apolipoprotein E (ApoE-/-) or low-density lipoprotein receptor (Ldlr-/-) knockout mice.
Main Results:
- Lana C induced depolarization and acidification in senescent HUVECs, leading to apoptosis.
- The senolytic effect of Lana C was dependent on caspase activation and potassium ion flux.
- Lana C treatment significantly reduced senescence burden and atherosclerotic lesion formation in mouse models.
Conclusions:
- Lanatoside C demonstrates significant senolytic activity, targeting senescent cells via Na+/K+-ATPase inhibition.
- Lana C effectively ameliorates aging hallmarks and cardiovascular pathology in vivo.
- Lana C represents a promising therapeutic candidate for age-related diseases.
