Almost all our detailed knowledge about the endothelium is proximate knowledge about its structure, development, and functioning, and how its dysfunctions lead to disease. The other, evolutionary half of endothelial biology has been neglected. Some researchers are unfamiliar with the fundamental distinction between proximate and evolutionary questions, and methods for formulating and testing evolutionary hypotheses about the endothelium remain underappreciated. This chapter offers a brief overview of the distinction between evolutionary and proximate explanations, followed by an introduction to evolutionary medicine and its applications to the endothelium.

Evolutionary, or Darwinian, medicine simply brings the power of evolutionary biology to bear on the problems of medicine. Some areas, such as pathogen evolution and population genetics, are well developed. Another aspect, emphasized in Darwinian medicine, is the enterprise of formulating and testing hypotheses about why natural selection has not shaped bodies that are more resistant to disease. The six key reasons for traits that leave bodies vulnerable to disease are reviewed below. Each is illustrated with examples from general medicine, and then with examples from a major disease of the endothelium, atherosclerosis.

TWO SEPARATE BIOLOGICAL QUESTIONS

Ernst Mayr passed away early in 2005 at age 100, shortly after publishing his twentieth book and the last of his 700+ scientific articles. One of his enduring contributions was his dogged emphasis on the importance of distinguishing proximate from evolutionary (sometimes called ultimate) biological explanations. His treatise, The Growth of Biological Thought, traces these two only-occasionally intersecting threads in biology: one that studies how things work (proximate), the other that studies why organisms are the way they are (evolutionary) (1). His final book, What Makes Biology Unique, continues and updates the theme (2).