We have previously shown that C1q is expressed on endothelial cells (ECs) of newly formed decidual tissue. Here we demonstrate that C1q is deposited in wound-healing skin in the absence of C4 and C3 and that C1q mRNA is locally expressed as revealed by real-time PCR and in situ hybridization. C1q was found to induce permeability of the EC monolayer, to stimulate EC proliferation and migration, and to promote tube formation and sprouting of new vessels in a rat aortic ring assay. Using a murine model of wound healing we observed that vessel formation was defective in C1qa^−/− mice and was restored to normal after local application of C1q. The mean vessel density of wound-healing tissue and the healed wound area were significantly increased in C1q-treated rats. On the basis of these results we suggest that C1q may represent a valuable therapeutic agent that can be used to treat chronic ulcers or other pathological conditions in which angiogenesis is impaired, such as myocardial ischemia. Significance C1q is a well-known initiator of the complement classical pathway and interacts with several immune and nonimmune cells inducing complement activation-independent functions. Endothelial cells represent one of the potential targets of C1q that binds to cell surface-expressed receptors and stimulates inflammation. Here we report a unique and hitherto unrecognized function of C1q to promote angiogenesis acting through the globular heads. The angiogenic activity of C1q was supported by its ability to induce new vessel formation in in vitro and in vivo models of wound healing. These findings have important implications for the treatment of clinical diseases associated with impaired angiogenesis such as chronic skin ulcers in diabetic patients.

Functional recovery after peripheral nerve injury depends on both improvement of nerve regeneration and prevention of denervation-related skeletal muscle atrophy. To reach these goals, in this study we overexpressed vascular endothelial growth factor (VEGF) by means of local gene transfer with adeno-associated virus (AAV). Local gene transfer in the regenerating peripheral nerve was obtained by reconstructing a 1-cm-long rat median nerve defect using a vein segment filled with skeletal muscle fibers that have been previously injected with either AAV2-VEGF or AAV2-LacZ, and the morphofunctional outcome of nerve regeneration was assessed 3 months after surgery. Surprisingly, results showed that overexpression of VEGF in the muscle-vein-combined guide led to a worse nerve regeneration in comparison with AAV-LacZ controls. Local gene transfer in the denervated muscle was obtained by direct injection of either AAV2-VEGF or AAV2-LacZ in the flexor digitorum sublimis muscle after median nerve transection and results showed a significantly lower progression of muscle atrophy in AAV2-VEGF-treated muscles in comparison with muscles treated with AAV2-LacZ. Altogether, our results suggest that local delivery of VEGF by AAV2-VEGF-injected transplanted muscle fibers do not represent a rational approach to promote axonal regeneration along a venous nerve guide. By contrast, AAV2-VEGF direct local injection in denervated skeletal muscle significantly attenuates denervation-related atrophy, thus representing a promising strategy for improving the outcome of post-traumatic neuromuscular recovery after nerve injury and repair.

Purpose: To report a retrospective evaluation of the 6-F Angio-Seal closure device in antegrade and retrograde common femoral artery (CFA) punctures during endovascular procedures in diabetic patients with critical limb ischemia (CLI). Methods: From January 2005 to March 2009, 2374 diabetic CLI patients underwent interventional procedures in the lower limbs at a single center under systemic anticoagulation (heparin 70 U/kg). In this population, 2016 patients (1184 men; mean age 69.6±9.1 years) had 2372 CFA punctures treated with either manual compression [205 punctures in 161 (8.0%) patients] or Angio-Seal deployment (2167 punctures in 1855 patients) and were eligible for this analysis. In the study cohort, there were 1889 antegrade CFA punctures closed with the device in 1626 (87.6%) patients compared to 278 retrograde punctures sealed in 229 (12.4%) patients. The complications from the antegrade CFA punctures were compared to those from retrograde closure and manual compression. Results: The success rate for achieving hemostasis after antegrade and retrograde Angio-Seal placement was 97.9% and 97.8%, respectively. Major complications following antegrade Angio-Seal deployment, retrograde Angio-Seal deployment, and manual compression occurred in 20/1889 (1.1%), 5/278 (1.8%), and 4/205 (2.0%) cases, respectively. All complications developed within 24 hours of the procedure. No further complications were recorded in the 18-month follow-up (range 1–36). The overall complication rates after antegrade puncture closure, retrograde puncture closure, and manual compression at 30 days was 2.5%, 4.0%, and 4.9%, respectively (p = NS). Conclusion: This retrospective study shows that the 6-F Angio-Seal is a valuable and safe vascular closure device for percutaneous transfemoral antegrade access in diabetic patients undergoing interventional procedures for CLI.