Daily administration of serum amyloid P in a mouse model of ischemic cardiomyopathy prevented fibrosis and significantly improved fractional shortening (43% vs 34%).
Does in vivo administration of serum amyloid P (SAP) prevent fibrosis and ventricular dysfunction in a mouse model of ischemia/reperfusion cardiomyopathy?
Serum amyloid P prevents ischemia/reperfusion-induced fibrosis and ventricular dysfunction in mice by interfering with the assumption of a fibroblast phenotype in a subset of monocytes.
Absolute Event Rate: 43% vs 34%
p-value: p=<0.05
We previously described a mouse model of fibrotic ischemia/reperfusion cardiomyopathy (I/RC) arising from daily, brief coronary occlusion. One characteristic of I/RC was the prolonged elevation of monocyte chemoattractant protein 1 (MCP-1), which was obligate to its phenotype and may contribute to the uptake of bloodborne cells. Here we describe in I/RC hearts a population of small spindle-shaped fibroblasts that were highly proliferative and expressed collagen I and alpha-smooth muscle actin (myofibroblast markers), CD34 (a precursor marker), and CD45 (a hematopoietic marker). These cells represented 3% of all nonmyocyte live cells. To confirm the cells' bone marrow origin, chimeric mice were created by the rescue of irradiated C57BL/6 mice with marrow from ROSA26, a congenic line expressing lacZ. I/RC resulted in a large population of spindle-shaped fibroblasts containing lacZ. We postulated that the fibroblast precursors represented a developmental path for a subset of monocytes, whose phenotype we have shown to be influenced by serum amyloid P (SAP). Thus, we administered SAP in vivo, which markedly reduced the number of proliferative spindle-shaped fibroblasts and completely prevented I/RC-induced fibrosis and global ventricular dysfunction. By contrast, SAP did not suppress the inflammation or chemokine expression seen in I/RC. SAP, a member of the pentraxin family, binds to Fcgamma receptors and modifies the pathophysiological function of monocytes. Our data suggest that SAP interferes with assumption of a fibroblast phenotype in a subset of monocytes and that SAP may be an important regulator in the linkage between inflammation and nonadaptive fibrosis in the heart.
Haudek et al. (Sat,) conducted a other in Ischemic cardiomyopathy. Serum amyloid P (SAP) vs. Mouse albumin (25 µg) or untreated was evaluated on Fractional shortening (p=<0.05). Daily administration of serum amyloid P in a mouse model of ischemic cardiomyopathy prevented fibrosis and significantly improved fractional shortening (43% vs 34%).