Editorial [Hot Topic: Current Strategies in Vascular Biology (Guest Editor: Elisabeth Deindl)]

The development and remodeling of vessels is a crucial process in many physiological and pathophysiological processes making it topic of in-depth research in laboratories all around the world. Vascular occlusive diseases as well as malignant tumors are head of death causing aliments in industrialized countries. The notion that tumor angiogenesis may have therapeutic implications in the control of tumor growth was already introduced 1971. This special issue of Current Pharmaceutical Biotechnology contains in depth reviews on latest and most important developments in therapeutic strategies aiming to modulate vascular growth in terms of angiogenesis and arteriogenesis. Up to date reviews on maintenance and function of microcirculatory processes as well as on development of tissue engineered vascular grafts are supplied. Finally, the issue is round by an article containing some critical aspects on the potential of stem cells in terms of clinical application. In the past decade, many angiogenesis inhibitors have been developed for clinical use in oncology. Since angiogenesis inhibitors are relatively less toxic than conventional chemotherapy and have a lower risk of drug resistance “anti-angiogenic chemotherapy” has become a novel approach in cancer therapy. However, the encouraging results of pre-clinical studies could not fully meet the high expectations at bed side making further studies necessary. In this issue W.W. Kilarski & A. Bikfalvi focus on screening systems used to investigate the mechanisms of tissue neovasculariziation and recent progresses in vessel targeted tumor therapy. Whereas it is the aim of scientists working in the field of tumor development to block angiogenesis, others are interested in processes of vascular function and maintenance under normal physiological conditions. Small arteries and arterioles play a key role in regulation organ blood flow. Striking differences with respect to behavior and sensitivity for metabolic or mechanical stimuli between arterioles of different size have been reported. Endothelial cells of muscular vessels crucially contribute to the control of vascular tone by the release of autocaids like endothelium-dependent hyperpolarizing factors (EDHFs). The special features and properties of small arteries and microcirculatory vessels with respect to endothelium are highlighted by the article of C. de Wit & S.E. Woelfle. The review by C. Kupatt stresses the role of the microcirculation in vascular occlusive diseases. He comes up with the concept that therapeutically induced angiogenesis, i.e. the sprouting of capillaries, may result in a backward signaling triggering the growth of blood supplying collateral arteries. It is known for many years that collateral arteries grow spontaneously as an adaptive response around arteries with progressive stenosis. Hypoxia, the most important stimulus for capillary sprouting is not required for arteriolar growth. However, it is more than a hypothesis that newly formed capillaries may cause the growth of upstream-located arterioles satisfying the oxygen and nutrient demand of ischemic tissue - in particular when keeping in mind that arteries supplying blood to a growing tumor also increase in diameter and size. The term arteriogenesis, defining the growth of pre-existing arteriolar connections into true collateral arteries was introduced by W. Schaper. With his studies on the growth of natural bypasses he opened a new field in research. The article by M. Heil & W. Schaper does not only describe the basic mechanisms of collateral artery growth but provides information about the most recent findings. The review gives insight into the prominent role of fluid shear stress causing an activation of arterioles as well as an attraction and extravasation of monocytes presenting growth factor and cytokine producing micro-factories. However, the role of individual growth factors as master regulators of arteriogenesis was overestimated for a long time as shown by disappointing results of clinical studies. Collateral artery growth is a multi-factorial process requiring a well-defined action of biomolecules in terms of time and space. Unless it is not investigated how the process triggering mechanical stress, the fluid shear stress, is translated into the biological response, even approaches with cell therapies based on paracrine acting factors will only result in the support of collateral artery growth but will never be able to induce arteriogenesis de novo. One discipline en vogue is the induction of growth of natural bypasses, the other one the development of tissue engineered vascular grafts. G.R. and J.H. Campbell present fascinating results of this new discipline. Synthetic vascular grafts were already introduced several decades ago. However, they are limited to high-flow low resistance conditions........