Sulfatides are associated with neointimal thickening after vascular injury.
ABSTRACT Sulfatides are known to be a native ligand of P-selectin. Platelet-leukocyte interaction via the cross-talk between P-selectin and Mac-1 (CD11b/CD18) plays an important role in the mechanism of neointimal thickening after vascular injury such as that seen in post-stent restenosis. However, the roles of sulfatides on restenosis have not been elucidated.
Serum sulfatide levels, P-selectin expression on the surface of platelets, and activated Mac-1 on the surface of neutrophils were serially measured using both coronary sinus and peripheral blood samples in 21 patients who underwent coronary stent implantation.
The trans-cardiac gradient (coronary sinus minus peripheral blood) of the sulfatide levels significantly increased at 15 min (-1.47+/-2.87 to 0.59+/-1.44 nmol/ml, p<0.001), compared to baseline levels. The maximum response of the trans-cardiac gradient of P-selectin expression on the surface of platelets at 15 min after stent implantation (R=0.55, p<0.01), and that of activated Mac-1 on the surface of neutrophils at 48 h (R=0.59, p<0.01), were both positively correlated with that of serum sulfatide levels at 15 min. The angiographic late lumen loss was correlated with the trans-cardiac gradient of sulfatide levels at 15 min (R=0.48, p<0.05), platelet P-selectin expression at 15 min (R=0.42, p<0.05) and activated neutrophil Mac-1 expression at 48 h (R=0.46, p<0.05), but not with values at other sampling points.
Sulfatides may play a physiological role on inflammation in vascular injury and the development of neointimal thickening.
- Journal of Experimental Medicine - J EXP MED. 01/2000; 192(2):193-204.
- [show abstract] [hide abstract]
ABSTRACT: The pathophysiology of restenosis involves early elements of direct injury to smooth muscle cells, deendothelialization, and thrombus deposition. Over time, this leads to smooth muscle cell proliferation/migration and extracellular matrix deposition. There is an increasing body of evidence to suggest that inflammation plays a pivotal role linking early vascular injury to the eventual consequence of neointimal growth and lumen compromise. The widespread use of coronary stents has fundamentally altered the vascular response to injury by causing a more intense and prolonged inflammatory state. Many of the cellular and molecular elements responsible for leukocyte recruitment have been elucidated, providing potential therapeutic targets for restenosis. This review seeks to provide an integrated view of the pathophysiology of restenosis that explains the central role of inflammation.Arteriosclerosis Thrombosis and Vascular Biology 12/2002; 22(11):1769-76. · 6.34 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow. We measured circulating CD34-positive mononuclear cells, activation of integrin Mac-1 on the surface of neutrophils, and plasma granulocyte-colony stimulating factor levels in 40 patients undergoing coronary stenting. After bare-metal stenting, CD34-positive cells increased, reaching a maximum on day 7 after stenting. The maximum change compared with baseline before stenting was more striking in patients with restenosis than without restenosis (332+/-108% versus 148+/-49%; P<0.05). In contrast, CD34-positive cells decreased after sirolimus-eluting stenting (72+/-21% on day 7). The change in CD34-positive cells on day 7 relative to baseline was closely correlated with that in activated Mac-1 at 48 hours (R=0.52, P<0.01) and that in granulocyte-colony stimulating factor levels at 24 hours (R=0.42, P<0.05). Cell culture assay on day 7 showed that mononuclear cells differentiated into CD31-positive endothelium-like cells after bare-metal stenting. In patients with restenosis, mononuclear cells differentiating into alpha-smooth muscle actin-positive smooth muscle-like cells also were observed. Implantation of sirolimus-eluting stents suppressed both types of differentiation. Stent implantation may induce differentiation of bone marrow cells into endothelial or smooth muscle cells. Endothelial cells may participate in reendothelialization, a protective reaction against vascular injury, whereas smooth muscle cells may participate in neointimal thickening and restenosis. Sirolimus-eluting stents appear to inhibit the mobilization and differentiation of bone marrow cells.Circulation 02/2007; 115(5):553-61. · 15.20 Impact Factor