THE MOLECULAR AND CELLULAR BIOLOGY OF HEART-FAILURE

Advances in molecular genetics established the basis for several famil ial cardiovascular diseases by identifying the mutated gene and its de fective protein. Polymorphisms in the angiotensin-converting enzyme ge ne were associated with inherited increases in circulating levels of t he enzyme and increased risk of myocardial infarction. Similar studies linked hypertension to variations in the angiotensinogen gene. Hypert rophic cardiomyopathy was linked in several families to mutations in t he myosin heavy chain gene, with preclinical diagnosis now demonstrate d, although many affected families have no identified errors in this g ene. Specific genes and proteins have been linked with Marfan syndrome , long QT syndrome, and the cardiomyopathies associated with hereditar y amyloidosis and myotonic dystrophy; dilated cardiomyopathy may soon join this list. These advances are leading to the emergence of gene th erapy. Antisense oligonucleotides can prevent smooth muscle cell growt h in injured rat arteries. Viral vectors containing recombinant DNA ca n supplement defective low-density lipoprotein receptor genes in hyper cholesterolemic rabbits, and human experiments have begun.