title: Nitric oxide and endothelin in the development of cardiac allograft vasculopathy. Potential targets for therapeutic interventions.
abstract: Extensive research has been carried out in recent years to discover the potential risk factors contributing to cardiac allograft atherogenesis. Injury to endothelial cells has been regarded as an important early mechanism in the development of transplant atherosclerosis; it leads to the manifestation of epicardial and microvascular endothelial dysfunction and development of intimal hyperplasia. Moreover, continuous minor endothelial cell damage contributes to endothelial dysfunction which reflects one of the first measurable steps in the cascade of atherogenesis without macroscopic evidence of vascular lesions. The discovery of two important vasoactive substances nitric oxide (NO) and endothelin (ET) has brought new insights but also new unsolved questions regarding the mechanisms leading to atherosclerosis. To date it is known that both substances play a major role in both prevention and development of atherosclerosis. NO appears to be protective in low concentrations by inhibiting leukocyte and platelet activation/adherence and smooth muscle cell proliferation. Impaired endothelial NO production, as one cause of endothelial dysfunction may occur in early stages of atherosclerosis before macroscopic lesions are evident. In addition, increased endothelin release also results in endothelial dysfunction by inducing vasoconstriction; it promotes vascular lesion formation due to endothelial- and vascular smooth muscle cell proliferation. Direct and indirect manipulation of both the NO and ET signal transduction systems may provide novel preventive and therapeutic approaches for limiting transplant atherogenesis and to treat native atherosclerosis. This review summarizes important experimental and clinical evidence which points to nitric oxide and endothelin as potential therapeutic targets in the process of cardiac allograft vasculopathy.
authors.affiliation: Department of Cardiac Surgery, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: S M
authors.initials: SM
authors.lastname: Wildhirt
authors.forename: S
authors.initials: S
authors.lastname: Weismüller
authors.forename: C
authors.initials: C
authors.lastname: Schulze
authors.forename: N
authors.initials: N
authors.lastname: Conrad
authors.forename: B
authors.initials: B
authors.lastname: Reichart
mesh_terms: D000818:Animals; D016232:Endothelins / Q000096:biosynthesis / Q000502:physiology*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D012307:Risk Factors; D015398:Signal Transduction; D014652:Vascular Diseases / Q000209:etiology*
chemical_list: D016232:Endothelins; D009569:Nitric Oxide