Peripheral chronic total occlusions treated with subintimal angioplasty and a true lumen re-entry device.

OBJECTIVE: We sought to verify how effective the Pioneer catheter (Medtronic, Inc., Minneapolis, Minnesota) is in overcoming the complexity of re-entry during subintimal angioplasty and provide a case series describing the technique. BACKGROUND: Subintimal angioplasty is effective in treating peripheral chronic total occlusions (CTO). However, this technique is often limited by the inability to re-enter the true lumen after subintimal crossing of the occluded segment. The Pioneer catheter was the first device to address this difficulty associated with subintimal angioplasty. METHODS: A retrospective review of 21 consecutive cases of peripheral CTOs requiring use of the Pioneer catheter were reviewed. The patients' demographics, indications for the procedure, location and extent of occlusion, lesion characteristics, technique, procedural success and complications were recorded. RESULTS: Twenty of 21 cases were procedurally successful (defined as < or = 30% post-procedure stenosis), for a rate of 95%. The most commonly occluded vessels were the common iliac artery and the superficial femoral artery. The average occlusion length was 107 mm (standard deviation = 87) with a range of 23-300 mm. Both antegrade and retrograde approaches were successful. There was only 1 complication in the study population. CONCLUSIONS: The Pioneer catheter is a re-entry device that is versatile and improves success rates of subintimal angioplasty, which may lead to improvement in the care of patients with CTOs. The cases series demonstrates the use of the Pioneer catheter in treating CTOs.

Endothelial cells modulate osteogenesis in calcifying vascular cells.

The potential role of vascular endothelium in atherosclerotic calcification is unknown. Endothelial cells (EC) express bone morphogenetic proteins (BMP), and EC-conditioned medium is osteoinductive in marrow stromal cells. To test whether EC are osteoinductive in vascular cells, we used calcifying vascular cells (CVC) that form nodules and mineralize in vitro. We established a coculture model with EC grown opposite CVC on membranes coated with collagen I or collagen IV, both of which are expressed in atherosclerotic lesions. On collagen I, EC did not alter CVC nodule formation, calcification or expression of the osteogenic marker Cbfa1, the chondrogenic marker collagen IX or smooth muscle cell alpha-actin. However, on collagen IV, EC abolished nodule formation and calcification, and expression of cell markers decreased, suggesting dedifferentiation. Matrix GLA protein (MGP), also expressed in atherosclerotic lesions, was added to CVC in coculture. Unexpectedly, MGP enhanced Cbfa1 expression in CVC on both collagen I and IV. The enhancement was most apparent on collagen IV, where calcification also increased. However, MGP did not restore nodule formation on collagen IV, suggesting that nodule formation and cell differentiation are separate processes. The effect of EC on CVC calcification was suppressed by noggin, an inhibitor of BMP activity, and in part mimicked by replacement of EC by BMP-2. Our results support a role for endothelium in vascular calcification, modulated by collagens and MGP.

Matrix GLA protein and BMP-2 regulate osteoinduction in calcifying vascular cells.

Expression of matrix GLA protein (MGP), an alleged calcification inhibitor, is increased in calcified arteries. We used calcifying vascular cells (CVC) that form calcified nodules in vitro to clarify the importance of MGP in vascular cell calcification and differentiation. Unexpectedly, MGP dose-dependently increased calcification in CVC. It also increased expression of the osteogenic marker Cbfal, while decreasing expression of the smooth muscle marker alpha-actin as assessed by immunoblotting. Bone morphogenetic protein-2 (BMP-2), a known osteoinductive factor also increased calcification and osteogenic differentiation in CVC. We hypothesized that the effect of MGP was linked to that of BMP-2 since previous studies show that MGP modulates BMP-2 activity. Therefore, we compared the effect of MGP at different levels of exogenous BMP-2. Results showed that high BMP-2 levels significantly increased the stimulatory effect of low levels of MGP. A relative inhibition of calcification was observed at intermediate levels of MGP and a trend towards renewed stimulation at high levels of MGP. Thus, addition of MGP either promoted or inhibited calcification, depending on the relative amounts of BMP-2 and MGP. This was confirmed in human CVC with different relative expression of BMP-2 and MGP. Calcification in CVC with high relative expression of BMP-2 was inhibited by MGP, while calcification in CVC with low relative expression of BMP-2 was stimulated by MGP. MGP and BMP-2 both accelerated nodule formation, but had opposite effects on nodule size; MGP decreased while BMP-2 increased nodule size. The effect of BMP-2 may partly be explained by a BMP-2 induced decrease in MGP expression. Together, our results suggest that the effect of MGP on calcification and osteogenic differentiation is determined by availability of BMP-2.