Vascular endothelial growth factor inhibits mitogen-induced vascular smooth muscle cell proliferation.

INTRODUCTION: Delivery of vascular endothelial growth factor (VEGF) protein or gene transfer has been shown to accelerate re-endothelialization and attenuate neointimal hyperplasia in various arterial injury models, including balloon injury, stent implantation, and vein grafts. In addition to stimulating re-endothelialization, we hypothesize that VEGF has further vascular protective functions to prevent neointimal hyperplasia by directly inhibiting mitogen-induced proliferation of vascular smooth muscle cells (VSMCs) via the mitogen-activated protein kinase pathway. MATERIALS AND METHODS: Human aortic VSMCs were seeded and serum starved for 24 h. The cells were then stimulated with a mitogen, recombinant human platelet derived growth factor at 20 ng/mL together with 0, 10, 20, 30, 40, 50 ng/mL recombinant human VEGF. A proliferation assay was used to quantitate bromodeoxyuridine uptake into newly synthesized DNA. Western immunoassay was used to quantify extracellular signal-regulated kinase (ERK) 2 protein and phosphorylation of retinoblastoma and ERK 1/2 protein. RESULTS: VEGF inhibited bromodeoxyuridine incorporation into mitogen-induced VSMC in a dose-dependent manner, reaching statistical significance at concentrations of 30 (P < 0.05), 40 (P < 0.05), and 50 ng/mL (P < 0.01). Densitometry of western immunoblots revealed an inhibition of phosphorylation of retinoblastoma at VEGF concentrations of 40 and 50 ng/mL and ERK 1/2 phosphorylation at concentrations of 30, 40 and 50 ng/mL. CONCLUSION: In addition to stimulating re-endothelialization, VEGF appears to have a vascular protective function by directly inhibiting VSMC proliferation. This effect occurs in the absence of endothelial cells and via the mitogen-activated protein kinase pathway. VEGF may serve as an important modulator of mitogen-induced VSMC proliferation after vascular injury.

The evolution of the axillofemoral bypass over two decades.

To determine if the indications and numbers of the axillofemoral bypass have changed, a retrospective analysis was performed of all patients undergoing axillofemoral bypass over the past two decades. Group A (1980-89) and group B (1990-99) were compared using demographics, comorbid illness, perioperative outcomes, and indications for operation. There were 33 extraanatomic bypasses performed in group A and 24 extraanatomic bypasses in group B. The average age in both group A and group B was 69 years. Males comprised a higher percentage in group B (75%) than in group A (55%). The percentage of smokers was roughly equivalent (group A 76%, group B 71%). Coronary artery disease was more prevalent in group A (85%) than in group B (63%). Diabetes mellitus was also more common in group A (33%) than in group B (21%). All of the grafts in group B were composed of PTFE and there were 2 early (30 day) failures (6%). There were no perioperative deaths, strokes, or myocardial infarctions. At our institution, the axillofemoral bypass is now reserved almost exclusively for the treatment of graft infections and rarely for primary limb ischemia. This evolution is a reflection of the increase in interventional techniques used to improve inflow in high-risk patients who require revascularization.

PhotoPoint photodynamic therapy with local drug delivery eliminates vessel wall cells in arteriovenous graft models.

PURPOSE: To demonstrate the feasibility of PhotoPoint photodynamic therapy (PDT) with local drug delivery, optimize dosimetry in a rabbit jugular vein model, and investigate its ability to deplete potential neointimal precursor cells in the vessel wall in a canine arteriovenous graft (AVG) model. METHODS AND MATERIALS: Photosensitizer MV2101 was administered locally in rabbit veins, incubated for 0-40 min and activated with external laser light. In canine veins, MV2101 was incubated for 30 min and activated by light. Tissues were excised at acute and chronic timepoints. RESULTS: PhotoPoint PDT reduced cell populations in both models with maximum depletions occurring at 20 min (> or = 100 J/cm2) in rabbit veins (> 90% depletion) and 30 min (200 J/cm2) in canine veins (> 85% depletion). Chronic veins revealed no evidence of PhotoPoint PDT-related abnormalities. CONCLUSIONS: PhotoPoint PDT with local MV2101 dramatically depleted potential neointimal precursor cells in the vessel wall. This suggests local drug delivery is feasible and that PhotoPoint PDT may be an efficacious treatment that could prolong AVG patency in the clinic.