The wnt-frizzled cascade in cardiovascular disease

Time for primary review 31 days. Wnt-proteins constitute a family of secreted cystein-rich glycosylated proteins, involved in a variety of modeling and remodeling processes including cell proliferation, differentiation, apoptosis and the control of cell orientation 1–3. Malfunctioning of the wnt-frizzled pathway has been implied in diseases as divergent as cancer and Alzheimer's disease 1, 4. The wnt-frizzled signal transduction pathway plays an important role during non-vertebrate and vertebrate development 5. Several studies have shown the importance of wnts in the control of processes such as patterning of the body axis and development of the central nervous system and the limbs 6, 7. Moreover, interventions in wnt signaling have been described to affect cardiac morphogenesis 8, 9 and several members of the wnt-frizzled signal transduction pathway were found to be expressed during cardiac development in vertebrates 10–14. In cardiovascular pathology, re-expression of a fetal gene expression pattern is a generally observed phenomenon 15. The study of gene expression during development may therefore provide clues about the expression profile during cardiovascular pathology. Recently, considerable progress has been made concerning the role of the wnt-frizzled signal transduction pathway in the development and progression of cardiovascular pathology. This review will focus on the possible role of the wnt-frizzled signal transduction pathway in cardiovascular diseases. The family of wnt proteins consists of 16 members 5. These proteins are extremely difficult to purify because they tend to bind to the extracellular matrix 16, which hampers the study of their characteristics. An overview of the wnt proteins and their proposed function during development, derived from the study of null mutants, is provided in Table 1. Based on functional differences, wnt proteins can be divided into two classes, the wnt1 class and the wnt5a class. Members of the wnt1 class are able … * Corresponding author. Tel.: +31-43-388-1417; fax: +31-43-388-4149 wm. blankesteijnatfarmaco. unimaas. nl