Table 1.
Studies of senotherapeutics in animal models of cardiovascular disease and their outcomes
| Model | Condition | Senolytic Treatment | Cellular Senescence Outcomes | Cardiovascular Outcomes | Reference |
|---|---|---|---|---|---|
| C57Bl/6 mice | Old age | D + Q | ↓SA-β-Gal and Cdkn2a expression | Improved ejection fraction and endothelial function | (17) |
| C57Bl/6 and INK-ATTAC mice | Old age | ABT-263 and genetic | ↓p16 abundance and DNA damage | Ameliorated myocardia hypertrophy and fibrosis | (18) |
| C57Bl/6 and INK-ATTAC mice | Old age | D + Q and genetic | ↓p16 abundance, SA-β-Gal, and DNA damage | Cardiac progenitor cell activation and cardiomyocyte formation | (19) |
| C57Bl/6 mice | Doxorubicin-induced heart failure | ABT-263 | ↓p16, p21 and p53 expression and abundance | Improved ejection fraction and cardiac function | (20) |
| C57Bl/6 mice | Angiotensin II-induced heart failure | ABT-263 | ↓p16 and p21 abundance | Improved ejection fraction | (21) |
| C57Bl/6 mice | High-fat diet-induced heart failure | Q | No change in SA-β-Gal and ↑Cdkn2a and p53 expression | Restored heart size and reduced fibrosis | (22) |
| C57Bl/6 mice | Ischemia-reperfusion injury in old mice | ABT-263 | ↓Cdkn2a expression | Increased survival following myocardial infarction | (23) |
| Fisher 344 rats | Ischemia-reperfusion injury | ABT-263 | ↓p16, p21, and SASP expression and abundance | Improved ejection fraction and cardiac function | (24) |
| C57Bl/6 mice | Myocardial infarction in old mice | D + Q | ↓p16 abundance and DNA damage | Improved left ventricular and cardiac function | (25) |
| C57Bl/6 mice | Myocardial infarction with reperfusion | ABT-263 | ↓Cdkn1a, Cdkn2a, and SASP expression | Ameliorated myocardial hypertrophy and fibrosis and improved ejection fraction | (26) |
| p16-3MR mice | Myocardial infarction with reperfusion | Genetic | ↓p16, p21, and SASP abundance | Improved ejection fraction and reduced fibrosis | (27) |
| C57Bl/6 and p16-3MR mice | Old age | ABT-263 and genetic | ↓p16 abundance | Improved endothelial function and reduced arterial stiffness | (28) |
| C57Bl/6 and p16-3MR mice | Old age | Fisetin | ↓p16 abundance | Improved endothelial function | (29) |
| C57Bl/6 mice | Old age and apoe KO-induced atherosclerosis | D + Q | ↓DNA damage | Improved vasomotor function, reduced arterial stiffness, and ameliorated atherosclerotic plaque | (30) |
| C57Bl/6 mice | Old age and apoe KO-induced atherosclerosis | BPTES | ↓SA-β-Gal and SASP abundance | Ameliorated atherosclerotic plaque | (31) |
| C57Bl/6 mice | Apoe KO-induced atherosclerosis | ABT-263 | ↓Cdkn2a expression and p21 abundance | Ameliorated atherosclerosclerotic plaque | (32) |
| p16-3MR mice | Apoe KO-induced atherosclerosis | ABT-263 and genetic | No change in Cdkn2a or SASP expression | Ameliorated atherosclerosclerotic plaque | (33) |
| C57Bl/6 mice | Apoe KO-induced atherosclerosis | GPNMB vaccine | ↓Cdkn1a and Cdkn2a expression and SA-β-Gal | Ameliorated atherosclerosclerotic plaque | (34) |
| p16-3MR mice | Ldlr KO-induced atherosclerosis | ABT-263 and genetic | ↓SA-β-Gal and Cdkn2a expression | Ameliorated atherosclerosclerotic plaque | (7) |
| C57Bl/6 and INK-ATTAC mice | Ldlr KO-induced atherosclerosis | ABT-263 and genetic | ↓SA-β-Gal | Ameliorated atherosclerosclerotic plaque | (35) |
| C57Bl/6 mice | Old mice and angiotensin II-induced abdominal aortic aneurysm | D + Q | ↓Cdkn1a and SASP expression | Ameliorated abdominal aortic aneurysm | (36) |
D + Q, dasatinib and quercetin; Q, quercetin; BPTES, bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide; GPNMB, glycoprotein nonmetastatic melanoma protein B; SA-β-Gal, senescence-associated β-galactosidase; SASP, senescence-associated secretory phenotype.