| First Author | Papageorgiou AP | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 94 |
| Issue | 1 | Pages | 115-24 |
| PubMed ID | 22308237 | Mgi Jnum | J:196622 |
| Mgi Id | MGI:5488871 | Doi | 10.1093/cvr/cvs077 |
| Citation | Papageorgiou AP, et al. (2012) Thrombospondin-2 prevents cardiac injury and dysfunction in viral myocarditis through the activation of regulatory T-cells. Cardiovasc Res 94(1):115-24 |
| abstractText | AIMS: Thrombospondin-2 (TSP-2) modulates matrix integrity and myocyte survival in the hypertensive or ageing heart. Whether TSP-2 may affect cardiac inflammation and injury, in particular during acute viral myocarditis, is completely unknown. METHODS AND RESULTS: Therefore, mortality, cardiac inflammation, and function were assessed in TSP-2-null (KO) and wild-type (WT) mice in human Coxsackie virus B3 (CVB3)-induced myocarditis. TSP-2 KO had an increased mortality when compared with WT mice during viral myocarditis. The absence of TSP-2 resulted in increased cardiac inflammation and injury at 14 days, which resulted in depressed systolic function [fractional shortening (FS); 34 +/- 2.6 in WT vs. 24 +/- 1.8 in KO mice, P< 0.05] and increased cardiac dilatation (end-diastolic dimensions, mm; 3.7 +/- 0.09 in WT vs. 4.8 +/- 0.06 in KO mice, P< 0.05) 35 days post-infection. Lack of TSP-2 resulted in a decreased activation of the anti-inflammatory T-regulatory cells, as indicated by a lower number of CD25-positive T-cells, and significantly decreased gene expression of regulatory T-cell markers, Foxp3 and CTLA-4. Finally, overexpression of TSP-2 in WT hearts using cardiotropic vectors derived from adeno-associated virus serotype 9 (AAV9) inhibited cardiac inflammation and injury at 14 days and improved cardiac function at 35 days post-CVB3 infection when compared with control AAV9. CONCLUSION: TSP-2 has a protective role against cardiac inflammation, injury, and dysfunction in acute viral myocarditis. |
