The clinical significance of endothelial dysfunction.
OBJECTIVE
Endothelial dysfunction is thought to play a pivotal role in the development, progression, and clinical complications of atherosclerosis. Several recent studies have addressed the clinical implications of endothelial dysfunction for cardiovascular events, atherosclerosis, restenosis, and heart failure. Novel findings with respect to endothelial progenitor cells and their alteration by cardiovascular risk factors are characterized and potential therapeutic interventions to improve endothelial and endothelial progenitor cell function are discussed.


RESULTS
Over the past 5 years evidence has accumulated from clinical studies for a close association of the degree of endothelial dysfunction and clinical cardiovascular events in patients with cardiovascular risk factors, coronary disease, acute coronary syndrome, or heart failure. Understanding of the mechanisms leading to endothelial dysfunction has improved, including the notion that dysfunctional endothelial nitric oxide synthase, in part due to deficiency of the endothelial nitric oxide synthase cofactor tetrahydrobiopterin, likely plays an important role. Major progress has been made in understanding the role of endothelial progenitor cells, which likely contribute to both ischemia-induced neovascularization and endothelial regeneration after injury. Endothelial progenitor cell function is altered in patients with cardiovascular risk factors.


CONCLUSIONS
Recent research on endothelial and endothelial progenitor cell dysfunction supports their clinical significance and has led to important insights in the pathophysiology of cardiovascular disease and at the same time provides an important opportunity to develop novel therapeutic approaches. Endothelial function represents a valuable surrogate endpoint to assess the impact of therapeutic interventions.
Landmesser
Ulf
U
Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany. Landmesser.Ulf@MH-Hannover.DE
Drexler
Helmut
H
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008019:Life Style; D019001:Nitric Oxide Synthase / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D012307:Risk Factors; D013234:Stem Cells / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019001:Nitric Oxide Synthase