How the endothelium and its bone marrow-derived progenitors influence development of disease.
The association between diseases accompanied by abnormal endothelial/vascular function (atherosclerosis, hypertension, diabetes mellitus, preeclampsia), and conditions characterized by increased tissue growth and normal endothelial/vascular function (cancer, placental size, birth length, adult height) could be caused by inherited characteristics of endothelial cells and their bone marrow-derived precursors. The genotype responsible for normal endothelial/precursor function could be modified by intrauterine and postnatal endothelial injury; telomere shortening caused by increased endothelial precursor proliferation in response to injury can result in premature endothelial senescence and a decreased precursor proliferative potential, thereby leading to an abnormal endothelial/precursor phenotype and the associated diseases. The individual endothelial/precursor phenotype could be established early in life and its changes in response to risk factors for diseases followed over time, thus providing a unique opportunity for identification and early institution of prophylactic and therapeutic interventions in diseases that cause most of the morbidity and mortality in advanced industrialized societies.