Neovascularization Of Ischemic Tissue Research Articles

Cardiac angiogenesis and gene therapy: a strategy for myocardial revascularization.

Angiogenesis, the de novo formation of new vasculature, is a critical response to ischemia that provides neovascularization of ischemic tissues. In therapeutic angiogenesis, an angiogen--a mediator that induces angiogenesis--is delivered to targeted tissues, augmenting the native angiogenic process and enhancing reperfusion of ischemic tissues. Gene transfer is a novel means of providing therapeutic angiogenesis: the cDNA coding for specific angiogens, rather than the proteins themselves, is administered to the tissues in which angiogenesis is desired. This review is focused on therapeutic angiogenesis based on gene transfer strategies for the provision of myocardial revascularization.

Impaired collateral vessel development associated with reduced expression of vascular endothelial growth factor in ApoE-/- mice.

The impact of disordered lipid metabolism on collateral vessel development was studied in apolipoprotein (apo)E-/- mice with unilateral hindlimb ischemia. Hindlimb blood flow and capillary density were markedly reduced in apoE-/- mice versus C57 controls. This was associated with reduced expression of vascular endothelial growth factor (VEGF) in the ischemic limbs of apoE-/- mice. Cell-specific immunostaining localized VEGF protein expression to skeletal myocytes and infiltrating T cells in the ischemic limbs of C57 mice; in contrast, T-cell infiltrates in ischemic limbs of apoE-/- mice were severely reduced. The critical contribution of T cells to VEGF expression and collateral vessel growth was reinforced by the finding of accelerated limb necrosis in athymic nude mice with operatively induced hindlimb ischemia. Adenoviral VEGF gene transfer to apoE-/- mice resulted in marked augmentation of hindlimb blood flow and capillary density. These findings thus underscore the extent to which hyperlipidemia adversely affects native collateral development but does not preclude augmented collateral vessel growth in response to exogenous cytokines. Moreover, results obtained in the apoE-/- and athymic nude mice imply a critical role for infiltrating T cells as a source of VEGF in neovascularization of ischemic tissues.

Vascular endothelial factor (VEGF): therapeutic angiogenesis and vasculogenesis in the treatment of cardiovascular disease

The formation of new blood vessel is essential for a variety of physiological processes like embryogenesis and the female reproduction as well as pathological processes like tumor growth, wound healing and neovascularization of ischemic tissue. Vasculogenesis and angiogenesis are the mechanisms responsible for the development of the blood vessels. While angiogenesis refers to the formation of capillaries from pre-existing vessels in the embryo and adult organism, vasculogenesis, the development of new blood vessels from in situ differentiating endothelial cells, has been previously considered restricted to embryogenesis. Recent investigations, however, show the existence of endothelial progenitor cells (EPCs) in the peripheral blood of the adult and their participation in ongoing neovascularization. Molecular and cell-biological experiments suggest that different cytokines and growth factors have a stimulatory effect on these bone-marrow derived EPCs. Results with GM-CSF (granulocyte macrophage-colony stimulating factor) and VEGF (vascular endothelial growth factor) open a new insight into the clinical use of cytokines and in particular the use of growth factors in gene therapy. The administration via protein or plasmid-DNA for neovascularization seems to enhance both pathways, angiogenesis and vasculogenesis.

Prospects for intravascular gene therapy

The goal of this review is to provide an overview of gene delivery systems and candidate genes currently being evaluated for genetic strategies in vascular gene therapy. We will discuss treatment strategies that have been shown by in vivo model systems to be efficacious in promoting neovascularization of ischemic tissue or limiting post-interventional restenosis by inhibiting smooth muscle cell proliferation and/or encouraging re-endothelialization.

Hyperbaric Oxygen Therapy in Plastic Surgery

The most important effects of hyperbaric oxygen (HBO), for the surgeon, are the stimulation of leukocyte microbial killing, the enhancement of fibroblast replication, and increased collagen formation and neovascularization of ischemic tissue. Preoperative hyperbaric oxygen induces neovascularization in tissue with radionecrosis. Refractory osteomyelitis and necrotizing fasciitis appear to respond to adjunctive hyperbaric oxygen. Crush injury and compartment syndrome appear to benefit through preservation of ATP in cell membranes, which limits edema. Hyperbaric oxygen in burn injury permits shorter hospital stays, a reduced number of surgeries, and less fluid replacement. Skin grafts and flaps are reported to take more completely and more rapidly. The same mechanisms may apply in ischemic problem wounds such as infected diabetic extremities. Contraindications and side effects are described. Hyperbaric oxygen will not heal normal wounds more rapidly but may, under certain circumstances, induce problem wounds to heal more like normal ones.

Angiogenic factor: A possible mechanism for neovascularization produced by omental pedicles

To determine possible mechanisms by which omental pedicles protect bronchial anastomoses from ischemia, we studied the angiogenic potential of a lipid extract of omentum. A rabbit cornea model was used to quantify neovascularization produced by methanol-chloroform extract of homogenized autologous omentum or perirenal fat. In 22 anesthetized rabbits, 10 microliters of omental lipid extract was injected into the cornea. In each animal the opposite eye was used as a control and was injected with a similar volume of extract prepared from perirenal fat. The side of injection of autologous omental fat was randomized and was not known to the investigator who assessed neovascularization on days 4, 7, 14, and 21 after injection. Neovascularization was recorded on microphotography and quantified by a point-counting method. Four days after injection, neovascularization in corneas injected with autologous omental fat was significantly (p less than 0.05) greater than in control corneas for all indices of neovascularization including total point count, which was three times greater than control. The angiogenic effect diminished with time, and by 21 days after injection corneal neovascularization was comparable for the two groups. Our results suggest that the lipid fraction of omentum has angiogenic activity that may stimulate neovascularization in ischemic tissues. Lack of sustained activity may be due to washout by neovessels or local tissue metabolism.