Arteriogenesis refers to the growth of collateral arteries after stenosis and is distinct from angiogenesis. Factors such as shear forces, vascular dilatation, and monocyte accumulation play a role in the process. In the future, patients will likely be able to undergo “natural” bypass by inducing arteriogenesis.
What is arteriogenesis?
Arteriogenesis refers to the growth of collateral arteries after stenosis and is distinct from angiogenesis. The growth of arteries from already established networks of small arterial connections is called arteriogenesis. In angiogenesis, on the other hand, entirely new blood vessels sprout from old, i.e. already existing, blood vessels. Arteriogenesis in the sense of a growth of so-called collateral arteries takes place after the occlusion of larger arteries, i.e. after stenoses. Arteriogenesis corresponds to the only physiologically efficient type of blood vessel growth and can compensate for blood circulation deficits. The stimulation of arteriogenesis is subject to physical forces, such as the shear stress that exists after stenoses due to increased blood flow within collateral arterioles. In addition, monocytes are thought to be stimulatory factors. They are the largest immune cells within the human blood. Unlike the related process of angiogenesis, arteriogenesis occurs in complete independence of oxygen supply and is thus not affected by hypoxia in the sense of reduced oxygen supply.
Function and Purpose
The process of arteriogenesis is initiated with the sustained dilatation of the vessel lumen, which leads to the accumulation of myocytes and hypertrophy of the endothelium. Arteriogenesis is triggered by stenoses that occlude a supplying blood vessel. The occlusion lowers the perfusion pressure. At the same time, increased shear forces occur in the remaining blood vessels, which activate the endothelium of the vessel. On the basis of this activation, an inflammatory reaction occurs in which nitric oxide and transcription factors are released. The relevant transcription factors include, above all, HIF-1α, the hypoxia-induced factor. Cytokines are released by the processes described, most notably MCP-1 or better monocyte chemotactic protein-1. In addition, inflammatory cells are activated, which include monocytes and macrophages. Gene expression of adhesion molecules, such as Intracellular Adhesion Molecule-1 and ICAM-1, is enhanced induced. During arteriogenesis, the original vessel diameter sometimes expands 20-fold, thus allowing adequate blood supply again. The Max Planck Society points out that arteriogenesis has been associated with the accumulation of monocytes in growing collateral vessel walls in a number of studies. The research group led by Wolfgang Schaper then investigated the origin of the cells and the role that circulating monocytes play in arteriogenesis. In experimental approaches, they increased and decreased the number of monocytes in the blood circulation of the animals. In the first group, they initiated a depletion of monocytes from the blood, and the blood concentration of immune cells increased several times from the normal value after about two weeks due to the rebound effect. The group with sustained monocyte depletion showed a significantly lower level of arteriogenesis after blood flow restoration than the control group. In contrast, the rebound group showed increased arteriogenesis. Through their study, the investigators were able to establish functional relationships between peripheral blood monocyte concentration and the extent of collateral vessel growth during arteriogenesis.
Diseases and disorders
Medical researchers hope to stimulate arteriogenesis in the future and offer new therapeutic options to patients with cardiovascular diseases in the future. For example, arteriogenesis could produce natural bypass flow. Currently, the bypass is still created artificially during surgery and serves to bridge passage obstacles. Bypass surgery involves creating a connection between the beginning and end of stenoses. Most often, this operation is performed on the heart, so especially in the case of severely narrowed or completely blocked coronary arteries that need to be bypassed. The bypass restores the sufficient blood supply to the heart muscle.Bypasses are used in vascular surgery, for example, for the treatment of late-stage shambladder disease or for the treatment of aneurysms. In cardiac surgery, coronary artery bypass is a commonly placed bypass for coronary artery disease. Veins or arteries are taken from the patient’s body or from deceased patients for placement and used for bypass. Artificial tissue such as Gore-Tex or otherwise artificial vascular prostheses are now also used. For example, no sufficiently long vein is available for an aorta replacement, so that so-called tubular prostheses are the only therapeutic option to date. As an alternative to bypass, vascular surgery uses implants as interposition devices to replace the entire section of the vessel affected by an obstacle to passage. With research progress and ongoing research efforts in arteriogenesis, an entirely new and completely natural option for the therapy of passage obstructions may become available. Passage obstructions are a relevant issue especially in the Western world, where diseases such as arteriosclerosis have already become common diseases due to lifestyle. In the case of arteriosclerosis, the vessels “calcify”, become rigid and thus not only promote heart attacks and strokes, but also crack formation in the vessel walls. Bypass surgery, and with it the possibility of induced arteriogenesis, is becoming increasingly relevant, especially against this background. However, induction of arteriogenic processes by external influence is not yet used in clinical practice.