Neovascularization is the natural formation of new

blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...

s ('' neo-'' + ''

vascular The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...

'' + '' -ization''), usually in the form of functional microvascular networks, capable of perfusion by

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

s, that form to serve as

collateral circulation Collateral circulation is the alternate circulation around a blocked artery or vein via another path, such as nearby minor vessels. It may occur via preexisting vascular redundancy (analogous to engineered redundancy), as in the circle of Wil ...

in response to local poor perfusion or

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

. Growth factors that inhibit neovascularization include those that affect endothelial cell division and differentiation. These growth factors often act in a

paracrine Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse ove ...

autocrine Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with pa ...

fashion; they include

fibroblast growth factor Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their ...

placental growth factor Placental growth factor (PlGF) is a protein that in humans is encoded by the ''PGF'' gene. Placental growth factor (PGF) is a member of the VEGF (vascular endothelial growth factor) sub-family - a key molecule in angiogenesis and vasculogenesis, ...

insulin-like growth factor The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF "a ...

hepatocyte growth factor Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts o ...

, and platelet-derived endothelial growth factor. There are three different pathways that comprise neovascularization:(1) vasculogenesis,(2) angiogenesis, and (3) arteriogenesis.

Three pathways of neovascularization

Vasculogenesis

Vasculogenesis is the de novo formation of blood vessels. This primarily occurs in the developing embryo with the development of the first primitive vascular plexus, but also occurs to a limited extent with post-natal vascularization. Embryonic vasculogenesis occurs when endothelial cells precursors (hemangioblasts) begin to proliferate and migrate into avascular areas. There, they aggregate to form the primitive network of vessels characteristic of embryos. This primitive vascular system is necessary to provide adequate blood flow to cells, supplying oxygen and nutrients, and removing metabolic wastes.

Angiogenesis

Angiogenesis is the most common type of neovascularization seen in development and growth, and is important to both physiological and pathological processes. Angiogenesis occurs through the formation of new vessels from pre-existing vessels. This occurs through the sprouting of new capillaries from post-capillary venules, requiring precise coordination of multiple steps and the participation and communication of multiple cell types. The complex process is initiated in response to local tissue ischemia or hypoxia, leading to the release of angiogenic factors such as

VEGF Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...

and

HIF-1 Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They are only present in parahoxozoan animals. Discovery The HIF transcriptional complex w ...

. This leads to vasodilatation and an increase in vascular permeability, leading to sprouting angiogenesis or

intussusceptive angiogenesis Intussusceptive angiogenesis also known as splitting angiogenesis, is a type of angiogenesis, the process whereby a new blood vessel is created. By intussusception a new blood vessel is created by splitting of an existing blood vessel in two. In ...

Arteriogenesis

Arteriogenesis is the process of flow-related remodelling of existing vasculature to create collateral arteries. This can occur in response to ischemic vascular diseases or increase demand (e.g. exercise training). Arteriogenesis is triggered through nonspecific factors, such as shear stress and blood flow.

Ocular pathologies

Corneal neovascularization

Corneal neovascularization is a condition where new blood vessels invade into the cornea from the limbus. It is triggered when the balance between angiogenic and antiangiogenic factors are disrupted that otherwise maintain corneal transparency. The immature new blood vessels can lead to persistent inflammation and scaring, lipid exudation into the corneal tissues, and a reduction in corneal transparency, which can affect visual acuity.

Retinopathy of prematurity

Retinopathy of prematurity is a condition that occurs in premature babies. In premature babies, the retina has not completely vascularized. Rather than continuing in the normal ''in utero'' fashion, the vascularization of the retina is disrupted, leading to an abnormal proliferation of blood vessels between the areas of vascularized and avascular retina. These blood vessels grow in abnormal ways and can invade into the vitreous humor, where they can hemorrhage or cause retinal detachment in neonates.

Diabetic retinopathy

Diabetic retinopathy, which can develop into proliferative diabetic retinopathy, is a condition where capillaries in the retina become occluded, which creates areas of ischemic retina and triggering the release of angiogenic growth factors. This retinal ischemia stimulates the proliferation of new blood vessels from pre-existing retinal venules. It is the leading cause of blindness of working age adults.

Age-related macular degeneration

In persons who are over 65 years old, age-related macular degeneration is the leading cause of severe vision loss. A subtype of age-related macular degeneration, wet macular degeneration, is characterized by the formation of new blood vessels that originate in the choroidal vasculature and extend into the subretinal space.

Choroidal neovascularization

ophthalmology Ophthalmology ( ) is a surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a medic ...

choroidal neovascularization Choroidal neovascularization (CNV) is the creation of new blood vessels in the choroid layer of the eye. Choroidal neovascularization is a common cause of neovascular degenerative maculopathy (i.e. 'wet' macular degeneration) commonly exacerbated ...

is the formation of a microvasculature within the innermost layer of the

choroid The choroid, also known as the choroidea or choroid coat, is a part of the uvea, the vascular layer of the eye, and contains connective tissues, and lies between the retina and the sclera. The human choroid is thickest at the far extreme rear ...

of the eye. Neovascularization in the eye can cause a type of

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

(neovascularization glaucoma) if the new blood vessels' bulk blocks the constant outflow of

aqueous humour The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posterio ...

from inside the eye.

Neovascularization and therapy

Ischemic heart disease

Cardiovascular disease is the leading cause of death in the world. Ischemic heart disease develops when stenosis and occlusion of coronary arteries develops, leading to reduced perfusion of the cardiac tissues. There is ongoing research exploring techniques that might be able to induce healthy neovascularization of ischemic cardiac tissues.

References

{{Reflist Angiology Medical terminology