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Introduction Coronary heart disease is the leading cause of death worldwide with an estimated 3.8 million men and 3.4 million women dying each year from this condition (Mackay et al. [...], The saphenous vein is the most commonly used bypass graft in patients with coronary artery disease. During routine coronary artery bypass, grafting the vascular damage inflicted on the vein is likely to stimulate the release of endothelin-1, a potent endothelium-derived vasoconstrictor that also possesses cell proliferation and inflammatory properties, conditions associated with vein graft failure. In both in vitro and in vivo studies, endothelin receptor antagonists reduce neointimal thickening. The mechanisms underlying these observations are multifactorial and include an effect on cell proliferation and cell/tissue damage. Much of the data supporting the beneficial action of endothelin-1 receptor antagonism at reducing intimal thickening and occlusion in experimental vein grafts were published over 20 years ago. The theme of the recent ET-16 conference in Kobe was 'Visiting Old and Learning New'. This short review article provides an overview of studies showing the potential of endothelin receptor antagonists to offer an adjuvant therapeutic approach for reducing saphenous vein graft failure and poses the question why this important area of research has not been translated from bench to bedside given the potential benefit for coronary artery bypass patients. Key words: endothelin-1, endothelin A receptor, endothelin B receptor, endothelin receptor antagonists, coronary artery disease, saphenous vein, bypass graft, neointima, patency. La veine saphene est le vaisseau qui est le plus souvent utilise comme greffon lors du pontage de patients atteints de coronaropathie. Lors d'un pontage aortocoronarien, les dommages vasculaires infliges a la veine sont susceptibles de stimuler la liberation d'endotheline 1, un puissant vasoconstricteur derive de l'endothelium qui est aussi dote de proprietes sur le plan inflammatoire et de la proliferation cellulaire, etats pathologiques associes a l'echec de la greffe veineuse. Dans les etudes in vitro comme in vivo, les antagonistes des recepteurs de l'endotheline permettent de reduire l'epaississement de la neointima. Les modes d'action sous-jacents de ces observations sont multifactoriels et comprennent un effet sur la proliferation cellulaire et les dommages cellulaires/tissulaires. Une grande partie des donnees a l'appui des bienfaits de l'antagonisme des recepteurs de l'endotheline 1 dans la reduction de l'epaississement de l'intima et l'occlusion dans des modeles experimentaux de greffes veineuses ont ete publiees il y a plus de 20 ans. Le theme du recent congres ET-16 a Kobe etait<> (ou << lecture des donnees anciennes et apprentissage de nouvelles donnees >>). Ce court article de synthese fournit un apercu d'etudes montrant la possibilite que des antagonistes des recepteurs de l'endotheline puissent permettre d'acceder a une approche therapeutique adjuvante en vue de rendre les echecs de la greffe de la veine saphene moins frequents, et pose la question a savoir pourquoi cet important champ de recherche n'est pas passe de la paillasse au chevet des patients etant donne les bienfaits que pourraient en tirer ceux d'entre eux qui subissent un pontage aortocoronarien. [Traduit par la Redaction] Mots-cles: endotheline-1, recepteur de l'endotheline A, recepteur de l'endotheline B, antagonistes des recepteurs de l'endotheline, coronaropathie, veine saphene, pontage, neointima, permeabilite.

SAP is selectively concentrated in amyloid deposits by its avid binding to all amyloid fibril types (2,3). SAP binding stabilizes amyloid fibrils, protects them from proteolysis in vitro (5) and [...], Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries (1). Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present (1). There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation (1). Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous (1). There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP) (2,3). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-D-proline compound CPHPC4, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.