Evolution of the heart from bacteria to man

This review provides an overview of the evolutionary path to the mammalian heart from the beginnings of life (about four billion years ago) to the present. Essential tools for cellular homeostasis and for extracting and burning energy are still in use and essentially unchanged since the appearance of the eukaryotes. The primitive coelom, characteristic of early multicellular organisms (similar to 800 million years ago), is lined by endoderm and is a passive receptacle for gas exchange, feeding, and sexual reproduction. The cells around this structure express genes homologous to NKX2.5/tinman, and gradual specialization of this "gastroderm" results in the appearance of mesoderm in the phylum Bilateria, which will produce the first primitive cardiac myocytes. Investment of the coelom by these mesodermal cells forms a "gastrovascular" structure. Further evolution of this structure in the bilaterian branches Ecdysoa (Drosophila) and Deuterostoma (amphioxus) culminate in a peristaltic tubular heart, without valves, without blood vessels or blood, but featuring a single layer of contracting mesoderm. The appearance of Chordata and subsequently the vertebrates is accompanied by a rapid structural diversification of this primitive linear heart: looping, unidirectional circulation, an enclosed vasculature, and the conduction system. A later innovation is the parallel circulation to the lungs, followed by the appearance of septa and the four-chambered heart in reptiles, birds, and mammals. With differentiation of the cardiac chambers, regional specialization of the proteins in the cardiac myocyte can be detected in the teleost fish and amphibians. In mammals, growth constraints are placed on the heart, presumably to accommodate the constraints of the body plan and the thoracic cavity, and adult cardiac myocytes lose the ability to re-enter the cell cycle on demand. Mammalian cardiac myocyte innervation betrays the ancient link between the heart, the gut, and reproduction: the vagus nerve controlling heart rate emanates from centers in the central nervous system regulating feeding and affective behavior.