Microvascular repair (angiogenesis) following trauma or surgery is a complex process that is triggered initially by hypoxia and inflammation. Angiogenesis is controlled by an integrated but extremely complex interaction between exogenous and intracellular factors that ultimately result in the reestablishment of a fully functioning microvascular system that services any given organ or tissue. Since an impairment of this process, particularly after surgery, may compromise the outcome of the procedure, further understanding of microvascular repair may be of great clinical importance. How metabolic factors and risk factors for vascular disease influence microvascular repair and how this can be obviated is therefore an area that needs to be
Angiogenesis: The formation of new microvessels from existing endothelial cells. The process involves the migration and proliferation of endothelial cells, which form tubes. These elongate until they reach another microvessel or capillary with which they connect to restore blood flow.
Endothelial cell: Specialized cells that line all blood vessels. Their principal functions are the prevention of thrombosis, the control of vascular tone, and microvessel formation. Endothelial cells possess the capacity to generate modulators of these functions, which include nitric oxide, prostacyclin, and peptide growth factors.
Migration: A process by which cells, including endothelial cells, move from one site to another. Migration is dependent on the intracellular cytoskeleton, which is formed principally of actin and myosin. Migration is orchestrated by the focal adhesion complexes that link sites of adhesion with intracellular actin.
Proliferation: A process by which cells, including endothelial cells, divide (replicate) and multiply; axiomatic in angiogenesis. Cell replication is a highly controlled and orchestrated process known as the cell cycle. Peptide growth factors, including vascular endothelial growth factor, are key initiators of cell proliferation.
addressed in further research.
Abo-Auda, W., and Benza, R. L. (2003). Therapeutic angiogenesis: Review of current concepts and future directions. J. Heart Lung Transplant. 22, 370-382. This review covers the current therapeutic applications of angiogenesis, as does the review by Carmeliet (2003). Both are indispensable reading.
Conway, E. M., Collen, D., and Carmeliet, P. (2001). Molecular mechanisms of blood vessel growth. Cardiovasc. Res. 49, 507-521; Carmeliet, P. (2003). Angiogenesis in health and disease. Nat. Med. 9, 653-660. Both these reviews are "must" reading. They provide the reader not only with up-to-date concepts and directions but with a superb basic grounding even for those not versed in the intricacies of angiogenesis.
Folkman, J. (2003). Angiogenesis and apoptosis. Semin. Cancer Biol. 13, 159-167. Apoptosis is a key factor in the stabilization and regression of newly formed microvessels that is likely to be a key line of research in the coming years. This review provides an excellent grounding for those interested in pursuing this area.
Li, J., Zhang, Y. P., and Kirsner, R. S. (2003). Angiogenesis in wound repair: Angiogenic growth factors and the extracellular matrix. Microsc. Res. Tech. 60, 107-114. Matrix proteins play an axiomatic role in mediating angiogenesis. This review provides an excellent and accessible overview of the topic.
Martin, A., Komada, M. R., and Sane, D. C. (2003). Abnormal angiogenesis in diabetes mellitus. Med. Res. Rev. 23, 117-145. Although this review focuses on diabetes, it highlights how disorders of metabolism and risk factors for cardiovascular disease can influence angiogenesis, which in turn can influence the progression of vascular disease.
Pugh, C. W., and Ratcliffe, P. J. (2003). Regulation of angiogenesis by hypoxia: Role of the HIF system. Nat. Med. 9, 677-684; Wenger, R. H.
(2002). Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression. FASEB J. 16, 1151-1162; De Boer, R. A., Pinto, Y. M., and Van Veldhuisen, D. J. (2003). The imbalance between oxygen demand and supply as a potential mechanism in the pathophysiology of heart failure: The role of microvascular growth and abnormalities. Microcirculation 10, 113-126. These three excellent reviews cover the emerging and complex relationship between hypoxia and angiogenesis. Hypoxia and its role in new microvessel growth is likely to become a prominent area of research in the coming years. Ware, J. A. (1999). Cellular mechanisms of repair. In: Angiogenesis and Cardiovascular Disease Ware, J. A., and Simons, J. A., eds., pp. 30-78. Oxford: Oxford University Press. This chapter gives a comprehensive overview of all the key components of angiogenesis, ranging from definitions to intracellular signal transduction. Indeed, this book as a whole is highly recommended as an ideal reference source and for all interested in angiogenesis and microvascular repair.
Dr. Jamie Jeremy is a Reader in Vascular Biology at The Bristol Heart Institute, UK. For the past 10 years Dr. Jeremy has focused his research on the pathophysiology of vein graft failure with a particular emphasis on the role of microvessel regrowth.
Dr. Michael Dashwood is a Senior Research Fellow in the Department of Clinical Biochemistry, Royal Free Hospital. His main research interests are the mechanisms underlying vein graft failure in patients undergoing coronary artery bypass surgery. Another major focus of research is the role of microvessels in various aspects of vascular disease.
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