| First Author | Xu Z | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 10 | Pages | 2038-47 |
| PubMed ID | 20009036 | Mgi Jnum | J:158855 |
| Mgi Id | MGI:4440720 | Doi | 10.1182/blood-2009-09-244962 |
| Citation | Xu Z, et al. (2010) Plasminogen activator inhibitor-1 (PAI-1) is cardioprotective in mice by maintaining microvascular integrity and cardiac architecture. Blood 115(10):2038-47 |
| abstractText | Although the involvement of plasminogen activator inhibitor-1 (PAI-1) in fibrotic diseases is well documented, its role in cardiac fibrosis remains controversial. The goal of this study was to determine the effect of a PAI-1 deficiency (PAI-1(-/-)) on the spontaneous development of cardiac fibrosis. PAI-1(-/-) mice developed pervasive cardiac fibrosis spontaneously with aging, and these mice displayed progressively distorted cardiac architecture and markedly reduced cardiac function. To mechanistically elucidate the role of PAI-1 in cardiac fibrosis, 12-week-old mice were chosen to study the biologic events leading to fibrosis. Although fibrosis was not observed at this early age, PAI-1(-/-) hearts presented with enhanced inflammation, along with increased microvascular permeability and hemorrhage. A potent fibrogenic cytokine, transforming growth factor-beta (TGF-beta), was markedly enhanced in PAI-1(-/-) heart tissue. Furthermore, the expression levels of several relevant proteases associated with tissue remodeling were significantly enhanced in PAI-1(-/-) hearts. These results suggest that PAI-1 is cardioprotective, and functions in maintaining normal microvasculature integrity. Microvascular leakage in PAI-1(-/-) hearts may provoke inflammation, and predispose these mice to cardiac fibrosis. Therefore, a PAI-1 deficiency contributes to the development of cardiac fibrosis by increasing vascular permeability, exacerbating local inflammation, and increasing extracellular matrix remodeling, an environment conducive to accelerated fibrosis. |
