[PDF][PDF] Molecular basis of cardiac performance. Plasticity of the myocardium generated through protein isoform switches.

B Nadal-Ginard, V Mahdavi - The Journal of clinical …, 1989 - Am Soc Clin Investig
B Nadal-Ginard, V Mahdavi
The Journal of clinical investigation, 1989Am Soc Clin Investig
Although the physiological properties of the myocardium and their dynamic character have
been the focus of intense re-search during the past three decades, the biochemical and
molecular correlates underlying cardiac performance for the most part remain poorly
understood. The central role of the myo-cardium in the maintenance of the cardiac output
notwith-standing, until very recently the prevailing view of the heart was that of a
biochemically very static organ. Therefore, it did not seem eitherparticularly interesting or …
Although the physiological properties of the myocardium and their dynamic character have been the focus of intense re-search during the past three decades, the biochemical and molecular correlates underlying cardiac performance for the most part remain poorly understood. The central role of the myo-cardium in the maintenance of the cardiac output notwith-standing, until very recently the prevailing view of the heart was that of a biochemically very static organ. Therefore, it did not seem eitherparticularly interesting or suitable to address major questions of cellular and molecular biology affecting normal and pathological states. As a consequence, theimpact of the newly developed techniques of recombinant DNA and genetic manipulation in transgenic animals on the under-standing of cardiac cellular and molecular biology has been less significant than on other fields of biomedical sciences. With few exceptions, the power of these new techniques and approaches is just beginning to be felt in the field of cardiovas-cular biology. This state of affairs is more surprising given the biomedical importance of the cardiovascular system in general and the myocardium in particular, as well as the large number of investigators dedicated to its study. This situation is due, at least in part, to the characteristics of the myocardium that, until recently, have made this organ a less than ideal model system for a molecular and genetic approach. Due to the essential role ofthe myocardium in the survival of the organism, most of the genetic mutations that significantly affect its development and/or function are likely to be lethal. This feature explains the very small number of muta-tions described so far affecting the myocardium either in human or animal models. This is in contrast with the large number of mutations affecting blood cells, the endocrine system, and metabolicpathways, amongothers. The existence of these mutations has provided the port of entry for the molecular dissection ofthese systems. In addition to the unavailability of mutations, the difficulty in obtaining repeated samples of the myocardium that are suitable for biochemical and molecu-lar analysis from the same animal has also slowed progress. Furthermore, the existence ofwell-characterized cell lines that can be grown in homogeneous populations and mutated at will are an almost essential requirement for the exploitation of
The Journal of Clinical Investigation