| First Author | Santos-Zas I | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 1483 |
| PubMed ID | 33674611 | Mgi Jnum | J:304977 |
| Mgi Id | MGI:6515174 | Doi | 10.1038/s41467-021-21737-9 |
| Citation | Santos-Zas I, et al. (2021) Cytotoxic CD8(+) T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling. Nat Commun 12(1):1483 |
| abstractText | Acute myocardial infarction is a common condition responsible for heart failure and sudden death. Here, we show that following acute myocardial infarction in mice, CD8(+) T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8(+) T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8(+) T cells. The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up. Our work unravels a deleterious role of CD8(+) T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8(+) T lymphocytes in the setting of acute myocardial infarction. |
