The molecular and cellular biology of heart failure

Advances in molecular genetics established the basis for several familial cardiovascular diseases by identifying the mutated gene and its defective protein. Polymorphisms in the angiotensin-converting enzyme gene were associated with inherited increases in circulating levels of the enzyme and increased risk of myocardial infarction. Similar studies linked hypertension to variations in the angiotensinogen gene. Hypertrophic cardiomyopathy was linked in several families to mutations in the myosin heavy chain gene, with preclinical diagnosis now demonstrated, although many affected families have no identified errors in this gene. Specific genes and proteins have been linked with Marfan syndrome, long QT syndrome, and the cardiomyopathies associated with hereditary amyloidosis and myotonic dystrophy; dilated cardiomyopathy may soon join this list. These advances are leading to the emergence of gene therapy. Antisense oligonucleotides can prevent smooth muscle cell growth in injured rat arteries. Viral vectors containing recombinant DNA can supplement defective low-density lipoprotein receptor genes in hypercholesterolemic rabbits, and human experiments have begun.