| First Author | Meléndez GC | Year | 2011 |
| Journal | Cardiovasc Res | Volume | 92 |
| Issue | 3 | Pages | 420-9 |
| PubMed ID | 21908647 | Mgi Jnum | J:191551 |
| Mgi Id | MGI:5462032 | Doi | 10.1093/cvr/cvr244 |
| Citation | Melendez GC, et al. (2011) Substance P induces adverse myocardial remodelling via a mechanism involving cardiac mast cells. Cardiovasc Res 92(3):420-9 |
| abstractText | AIMS: Substance P and neurokinin A (NKA) are sensory nerve neuropeptides encoded by the TAC1 gene. Substance P is a mast cell secretagogue and mast cells are known to play a role in adverse myocardial remodelling. Therefore, we wondered whether substance P and/or NKA modulates myocardial remodelling via a mast cell-mediated mechanism. METHODS AND RESULTS: Volume overload was induced by aortocaval fistula in TAC1(-/-) mice and their respective wild types. Left ventricular internal diameter of wild-type (WT) fistulas increased by 31.9%; this was prevented in TAC1(-/-) mice (4.2%). Matrix metalloproteinase (MMP) activity was significantly increased in WT fistula mice and was prevented in TAC1(-/-) mice. Myocardial collagen volume fraction was decreased in WT fistula mice; this collagen degradation was not observed in the TAC1(-/-) group. There were no significant differences between any groups in tumour necrosis factor (TNF)-alpha or cell death. Cardiac mast cells were isolated from rat hearts and stimulated with substance P or NKA. We found that these cells degranulated only to substance P, via the neurokinin-1 receptor. To determine the effect of substance P on mast cells in vivo, volume overload was created in Sprague-Dawley rats treated with the NK-1 receptor antagonist L732138 (5 mg/kg/day) for a period of 3 days. L732138 prevented: (i) increases in cardiac mast cell density; (ii) increased myocardial TNF-alpha; and (iii) collagen degradation. CONCLUSIONS: Our studies suggest that substance P may be important in mediating adverse myocardial remodelling secondary to volume overload by activating cardiac mast cells, leading to increased TNF-alpha and MMP activation with subsequent degradation of the extracellular matrix. |
