Adenoviral VEGF-D gene therapy for myocardial ischemia.

Cardiovascular diseases are the leading cause of death globally. In spite of the availability of improved treatments, there is still a large group of chronic ischemia patients who suffer from significant symptoms and disability. Thus, there is a clear need to develop new treatment strategies for these patients.

AdVEGF-B186 and AdVEGF-DΔNΔC induce angiogenesis and increase perfusion in porcine myocardium.

Objective: Coronary heart disease remains a significant clinical problem, and new therapies are needed especially for patients with refractory angina for whom the current therapies do not provide sufficient relief. The aim of this study was to find out if angiogenic gene therapy using new members of the vascular endothelial growth factor (VEGF) family, VEGF-B and VEGF-D, increase myocardial perfusion as measured by the positron emission tomography (PET) O-imaging, and whether there would be coronary steal effect to the contralateral side. Furthermore, safety of intramyocardial angiogenic adenoviral gene transfer was evaluated.

VEGF-C and VEGF-C156S in the pro-lymphangiogenic growth factor therapy of lymphedema: a large animal study.

Introduction: VEGF-C156S, a lymphangiogenesis-specific form of vascular endothelial growth factor C (VEGF-C), has been considered as a promising candidate for the experimental pro-lymphangiogenic treatment, as it lacks potential angiogenic effects. As a precursor to future clinical trials, the therapeutic efficacy and blood vascular side effects of VEGF-C and VEGF-C156S were compared in a large animal model of secondary lymphedema. Combination of lymphatic growth factor treatment and autologous lymph node transfer was used to normalize the lymphatic anatomy after surgical excision of lymphatic tissue.

HIF-1α and HIF-2α induce angiogenesis and improve muscle energy recovery.

Background: Cardiovascular patients suffer from reduced blood flow leading to ischaemia and impaired tissue metabolism. Unfortunately, an increasing group of elderly patients cannot be treated with current revascularization methods. Thus, new treatment strategies are urgently needed.

The bottleneck stent model for chronic myocardial ischemia and heart failure in pigs.

A large animal model of chronic myocardial ischemia and heart failure is crucial for the development of novel therapeutic approaches. In this study we developed a novel percutaneous one- and two-vessel model for chronic myocardial ischemia using a stent coated with a polytetrafluoroethylene tube formed in a bottleneck shape. The bottleneck stent was implanted in the proximal left anterior descending (LAD) or proximal circumflex artery (LCX), or in both proximal LCX and mid LAD 1 wk later (2-vessel model), and pigs were followed for 4-5 wk.

Lymph node transfer and perinodal lymphatic growth factor treatment for lymphedema.

Objective: Our objective was to define the optimal growth factor treatment to be used in combination with lymph node transfer to normalize lymphatic vascular anatomy.

Background: In the lymph node transfer method, lymphatic anastomoses are expected to form spontaneously. However, lymphangiogenic growth factor therapies have shown promising results in preclinical models of lymphedema.

Neuropilin-2 and vascular endothelial growth factor receptor-3 are up-regulated in human vascular malformations.

Despite multiple previous studies in the field of vascular anomalies, the mechanism(s) leading to their development, progression and maintenance has remained unclear. In this study, we have characterized the expression levels of vascular endothelial growth factors and their receptors in 33 human vascular anomalies. Analysis with quantitative real-time PCR and gene-specific assays showed higher expression of neuropilin-2 (NRP2) and VEGF-receptor-3 (VEGFR-3) mRNAs in vascular malformations (VascM) as compared to infantile hemangiomas (Hem).

Antegrade in situ fenestration of aortic stent graft: in-vivo experiments using a pig model.

Background: Short proximal neck of an abdominal aortic aneurysm is associated with risk of treatment failure during abdominal aortic repair. Important side branches, such as renal arteries, cannot be covered without serious consequences.

Purpose: To test the feasibility of preoperative fenestration of abdominal aortic stent grafts with a re-entry catheter and steerable sheath to preserve the patency of renal arteries in an animal model.

Growth factor therapy and autologous lymph node transfer in lymphedema.

Background: Lymphedema after surgery, infection, or radiation therapy is a common and often incurable problem. Application of lymphangiogenic growth factors has been shown to induce lymphangiogenesis and to reduce tissue edema. The therapeutic effect of autologous lymph node transfer combined with adenoviral growth factor expression was evaluated in a newly established porcine model of limb lymphedema.