MOLECULAR AND CELLULAR PATHOPHYSIOLOGY OF HEART-FAILURE

The science and technology of molecular biology promises to revolutionize the understanding of the basis and treatment for many diseases. The focus of this review is its influence on knowledge of the pathophysiology of heart failure in the past year. Heart failure is a syndrome, and the molecular genetic basis for some single-gene diseases of the cardiovascular system has been determined, whereas the basis for the more common polygenic disorders is under investigation. Gene cloning as well as biochemical and cellular physiology studies have contributed insights into the basis for abnormal cardiac function in heart failure as influenced by a number of factors, eg, myocyte calcium homeostasis, myofibrillar proteins, cardiac neuroendocrine systems, myocyte energetics and myocardial development, growth and hypertrophy. Recombinant DNA, already an established part of new drug development, ushered in the new era of gene therapy. Initiated in experimental models, gene therapy in human cancer has already begun, whereas application to cardiovascular disease is under development.