Improving our insights into the genetic predisposition to cardiovascular disease is one of the most important challenges in our field in the next millennium, not only to unravel the cause of disease but also to improve the selection of patients for particular treatments. Nowadays, for example, subjects with a cholesterol above a particular plasma level are exposed to a cholesterol lowering regime based upon the beneficial outcome of epidemiological studies which include subjects not prone to the disease, despite a plasma cholesterol above the accepted level. Identification of the patients who are genetically predisposed to the consequences of this disorder will reduce the number of subjects unnecessarily treated and, hence, the costs of health care. Because in most cardiovascular diseases the genetic component is a consequence of more than one gene defect, only limited progress has as yet been made in identifying subjects genetically at risk. For example, in hypertension only in less than 10% of the patients the genetic defect has been identified. It has been known for quite some time that in heart and blood vessels fetal genes are as high blood pressure and upregulated or induced when they are exposed to such disorders ischemia. Little is known about the function of these genes in the cardiac and vascular adaptation to these disorders; only guesses can be made.

Inhalt

1. Cardiology approaching the year 2000. A clinician's look at molecular cardiology.- One: Cardiovascular specific gene expression.- 2. The transcriptional building blocks of the heart.- 3. A cardiac-specific troponin I promoter. Distinctive patterns of regulation in cultured fetal cardiomyocytes, adult heart and transgenic mice.- 4. Mice deficient in muscle LIM protein (MLP) reveal a pathway to dilated cardiomyopathy and heart failure.- 5. Regulation of endothelial cell specific receptor tyrosine kinase gene expression during development and disease.- 6. Smoothelins: one gene, two proteins, three muscle cell types .... so far.- Two: Transcription regulation.- 7. Regionalization of transcriptional potential in the myocardium: 'cardiosensor' transgenic mice.- 8. Human troponin genes: transcriptional regulation and chromosomal organization.- 9. Retinoid signaling: insight from genetically engineered mice.- 10. Ventricular expression of the atrial regulatory myosin light chain gene.- 11. Expression of rat gap junction protein connexin 40 in the heart.- three: Ion channels and gap junction.- 12. Sympathetic regulation of cardiac delayed rectification: relationship to cardiac arrhythmias.- 13. The sarco(endo)plasmic reticulum Ca2+ pumps in the cardiovascular system.- 14. Potassium channels; genes, proteins, and patients.- 15. Expression of Cx43 in cardiac and aortic muscle cells of hypertensive rats.- 16. Genetic engineering and cardiac ion channels.- four: Intracellular signaling.- 17. Receptor tyrosine kinase signaling in vasculogenesis and angiogenesis.- 18. Molecular analysis of vascular development and disorders.- 19. Crosstalk between the estrogen receptor and the insulin-like growth factor (IGF-1) receptor. Implications for cardiac disease.- 20. Expression ofbasic helix-loop-helix proteins and smooth muscle phenotype in the adult rat aorta.- 21. Expression of the IGF system in acute and chronic ischemia.- 22. Long-chain fatty acids and signal transduction in the cardiac muscle cell.- five: DNA transfer.- 23. Reduction of kidney renin expression by ribozymes.- 24. Receptor-dependent cell specific delivery of antisense oligonucleotides.- 25. Tissue-specific gene delivery by recombinant adenoviruses containing cardiac-specific promoters.- 26. Catheter-mediated delivery of recombinant adenovirus to the vessel wall to inhibit restenosis.