Publications

Hematopoietic stem cell transplantation has evolved as a central treatment modality in the management of different hematologic malignancies. Despite adequate posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in the hematopoietic stem cell transplantation setting, even in patients who receive human leukemic antigen (HLA) identical sibling grafts. Up to 30% of the recipients of stem cells or bone marrow transplantation from HLA-identical related donors and most patients who receive cells from other sources (matched-unrelated, non-HLA-identical siblings, cord blood) will develop > Grade 2 acute GVHD despite immunosuppressive prophylaxis. Thus, GVHD continues to be a major limitation to successful hematopoietic stem cell transplantation. In this review, the authors summarize the most current knowledge on the pathophysiology, clinical manifestations, and management of this potentially life-threatening transplantation complication.

The endothelium integrates and modulates critical functions of the arterial wall. As well as regulating vasomotion, it controls inflammation, coagulation, and thrombosis. Many of these actions are mediated through the release of nitric oxide. Endothelial dysfunction is associated with atherosclerosis and its risk factors. It is independently correlated to adverse cardiovascular events, including myocardial infarction, coronary death, and the need for revascularization. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) protect against cardiovascular death, myocardial ischemia, myocardial infarction, and stroke. Although cholesterol reduction accounts for some of these benefits, others appear to be independent of cholesterol lowering. The endothelium mediates many of these "lipid-dependent" and "lipid-independent" actions of statins. This chapter reviews the effects of statins on endothelial dysfunction. To do so, a brief outline of the biology of the endothelium is a prerequisite. This will be followed by a summary of the advances in vascular research on cholesterol-dependent and cholesterol-independent effects of statins, with a focus on the endothelium. Ultimately, clinical relevance of observations derived from basic biology will be discussed.