부산대학교 도서관

Cyclin-dependent kinase inhibitors, including [p21.sup.Cip1], are implicated in cell turnover and are active players in cardiovascular wound repair. Here, we show that [p21.sup.Cip1] orchestrates the complex interactions between local vascular and circulating immune cells during vascular wound repair. In response to femoral artery mechanical injury, mice with homozygous deletion of [p21.sup.Cip1] displayed accelerated proliferation of VSMCs and increased immune cell infiltration. BM transplantation experiments indicated that local [p21.sup.Cip1] plays a pivotal role in restraining excessive proliferation during vascular wound repair. Increased local vascular stromal cell--derived factor-1 (SDF-1) levels were observed after femoral artery injury in p21+/+ and p21-/- mice, although this was significantly greater in p21-/- animals. In addition, disruption of SDF-1/CXCR4 signaling inhibited the proliferative response during vascular remodeling in both p21+/+ and p21-/- mice. We provide evidence that the JAK/STAT signaling pathway is an important regulator of vascular SDF-1 levels and that [p21.sup.Cip1] inhibits STAT3 binding to the STAT-binding site within the murine SDF-1 promoter. Collectively, these results suggest that [p21.sup.Cip1] activity is essential for the regulation of cell proliferation and inflammation after arterial injury in local vascular cells and that the SDF-1/CXCR4 signaling system is a key mediator of vascular proliferation in response to injury.
Introduction Vascular wound repair is controlled by the interaction of local vascular cells (endothelial and smooth muscle) and infiltrating inflammatory cells (macrophages, neutrophils, and lymphocytes). Particularly during arterial wound healing, [...]