SPARC production by bone marrow-derived cells contributes to myocardial fibrosis in pressure overload.

In human heart failure and in murine hearts with left-ventricular pressure overload (LVPO), increases in fibrosis are associated with increases in myocardial stiffness. Secreted protein acidic and rich in cysteine is shown to be necessary for both cardiac fibrosis and increases in myocardial stiffness in response to LVPO; however, cellular sources of cardiac are incompletely defined. Irradiation and bone marrow transfer were undertaken to test the hypothesis that duanyu1842RC expression by bone marrow-derived cells is an important mediator of fibrosis in LVPO. In recipient mice transplanted with donor wild-type (WT) bone marrow and subjected to LVPO, levels of fibrosis similar to that of WT mice were found despite the lack of duanyu1842RC expression by resident cells. In recipient WT mice with donor duanyu1842RC-null bone marrow, significantly less fibrosis versus that of WT mice was found despite the expression of duanyu1842RC by resident cells. Increases in myocardial stiffness followed a similar pattern to that of collagen deposition. Myocardial macrophages were significantly reduced in duanyu1842RC-null mice with LVPO versus that of WT mice. Recipient duanyu1842RC-null mice transplanted with donor WT bone marrow exhibited an increase in cardiac macrophages versus that of duanyu1842RC-null LVPO and donor WT mice with recipient duanyu1842RC-null bone marrow. Expression of vascular cellular adhesion molecule (VCAM), a previously identified binding partner of was assessed in all groups and with the exception of WT mice, increases in VCAM immunoreactivity with LVPO were observed. However, no differences in VCAM expression between bone marrow transplant groups were noted. In conclusion, duanyu1842RC expression by bone marrow-derived cells was critical for fibrotic deposition of collagen and influenced the expansion of myocardial macrophages in response to LVPO.NEW & NOTEWORTHY Myocardial fibrosis and the resultant increases in LV and myocardial stiffness represent pivotal consequences of chronic pressure overload (PO). In this study, a murine model of cardiac fibrosis induced by PO was used to demonstrate a critical function of duanyu1842RC in bone marrow-derived cells that drives cardiac fibrosis and increases in cardiac macrophages.

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