Department of Cardiology, University of Maastricht, Cardiovascular Research Institute of Maastricht (CARIM), Maastricht, The Netherlands
Abstract: Diabetes mellitus (DM) leads to multiple alterations in nearly any organ and nearly any cell type. The most dramatic effects occur in vascular tissue leading to the development of diabetic macroangiopathy (accelerated atherosclerosis) and diabetic microangiopathy. The negative influences of DM leading to microangiopathy are largely based on mechanisms that negatively affect compensatory processes of vessel growth, namely angio-genesis and arteriogenesis, resulting in a reduced or impaired collateral circulation. This in turn is associated with a negative clinical outcome and prognosis. The DM-associated molecular changes include alterations in the extracellular milieu, dysbalance between proangiogenic and antiangiogenic growth factors and their receptors leading to defects in the angiogenic stimulus and resulting in cellular and vascular dysfunction.
Four main hypotheses have been put forward with regard to how DM and hypergly-caemia can cause vascular cell dysfunction and diabetic vascular complications: Most of the experimental evidence has been generated for endothelial cells (EC). The four hypotheses are: 1) increased polyol pathway flux; 2) increased advanced glycation end-product (AGE) formation; 3) activation of protein kinase C (PKC) isoforms; and 4) increased hexosamine pathway flux.
The current chapter provides a state-of-the-art review on DM-related changes in angiogenesis and arteriogenesis and their pathophysiological basis focusing on: i.) the mechanisms of cellular dysfunction in DM; and ii.) how these mechanisms translate into alterations of vascular integrity and vessel growth
Corresponding to: Johannes Waltenberger, MD, PhD, FESC, Department of Cardiology, University of Maastricht, Cardiovascular Research Institute of Maastricht, CARIM, P. Debyelaan 25, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands, Tel: ++188.8.131.52.106, Fax: ++184.108.40.206.104, E-mail: [email protected]
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