The role of the red blood cell and platelet in the evolution of mammalian and avian endothermy.

This review presents evidence to support the hypothesis that the reduced O2 during the Permian/Triassic period was the impetus for the evolutionary selection of endothermic animals. The evolution of smaller red blood cells with greater surface areas along with increased: capillary density, capillary surface area, hematocrits, blood pressure, blood flow rates, and shear rates were critical for efficient gas exchange in endothermy. The evolution of the four-chambered mammalian/avian heart allowed for low pulmonary and high systemic blood pressure. It is proposed that hypoxia-induced angiogenesis led to increased vascularization in endothermic animals. The increased blood pressure, flow rates, and shear forces likely required changes in hemostatic mechanisms that were met in mammals by the evolution of anucleate platelets. The evolution of mammals and birds occurred in a parallel fashion with further genetic changes to anucleate RBCs/platelets occurring in mammals. Although it is possible that the evolution of endothermy in birds and mammals occurred as two independent events, it is more likely that a common ancestor developed genetic mutations that laid down the road map for parallel alterations of their cardiovascular system in response to environmental pressures. Model systems to support the proposed changes from ectotherm to endotherm were developed from published data. The evolutionary development of endothermy occurred over millions of years with a continuum of genetic alterations that involved skeletal, soft tissue, cardiovascular macrochanges along with numerous molecular alterations. Genetic signals and potential regulators for the evolutionary changes of endothermic blood cells from their bipotential stem cells are also proposed.