| First Author | Riley HJ | Year | 2021 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 320 |
| Issue | 2 | Pages | H604-H612 |
| PubMed ID | 33306449 | Mgi Jnum | J:300047 |
| Mgi Id | MGI:6501089 | Doi | 10.1152/ajpheart.00552.2020 |
| Citation | Riley HJ, et al. (2020) SPARC Production by Bone Marrow-Derived Cells Contributes to Myocardial Fibrosis in Pressure-Overload. Am J Physiol Heart Circ Physiol 320(2) |
| abstractText | In human heart failure and in murine hearts with left ventricular pressure overload (LVPO), increases in fibrosis are associated with increases in stiffness. Secreted Protein Acidic and Rich in Cysteine (SPARC) is necessary for both cardiac fibrosis and increases in myocardial stiffness in response to LVPO, however cellular sources of cardiac SPARC are incompletely defined. Irradiation and bone marrow transfer were undertaken to test the hypothesis that SPARC expression by bone marrow-derived cells is an important mediator of fibrosis in LVPO. In recipient SPARC-null mice transplanted with donor wild-type (WT) bone marrow and subjected to LVPO, levels of fibrosis similar to that of WT hearts were found despite the lack of SPARC expression by resident cells. In recipient WT mice with donor SPARC-null bone marrow, significantly less fibrosis versus that of WT was found despite the expression of SPARC by resident cells. Increases in myocardial stiffness followed a similar pattern to that of collagen deposition. Myocardial macrophages were significantly reduced in SPARC-null mice with LVPO versus that of WT hearts. Recipient SPARC-null mice transplanted with donor WT bone marrow exhibited an increase in cardiac macrophages versus that of SPARC-null LVPO and donor WT mice with recipient SPARC-null bone marrow. Expression of Vascular Cellular Adhesion Molecule (VCAM) was found to be in increased in all groups with LVPO with the exception of WT mice. In conclusion, SPARC expression by bone marrow-derived cells was critical for fibrotic deposition of collagen and influenced the expansion of myocardial macrophages in response to LVPO. |
