Bone morphogenic protein-4: a potential novel target for preventing vein graft failure in coronary revascularization

Coronary artery bypass surgery is an effective and durable therapy in both acute coronary syndrome and chronic coronary stenotic disease refractory to pharmacological treatment. Despite rapid development in operation-specific technologies and secondary prevention measures, the benefits of surgical revascularization are largely limited by inadequate patency of one of the most commonly used conduits, namely the autologous saphenous vein. However, apart from antiplatelet and lipid-lowering drugs, no other pharmacologic agent has hitherto proven clinically effective in preventing short- and long-term vein graft failure. Aiming at a large number of known biomolecules, multiple promising strategies failed to translate their beneficial effects observed in animal models into the clinical settings. Bone morphogenic protein-4 (BMP4), originally identified as a mediator in bone formation, has been recently demonstrated to participate in the process of arterial post-injury remodeling. Existing evidence has demonstrated that BMP4 is closely involved in the pathogenesis of thrombus formation, neointimal hyperplasia and superimposed atherosclerosis, all of which significantly contribute to arterial stenotic lesions. Although the post-injury responses inherent to arterial and venous vessel are unique, they share common elements and present with similar physiologic characteristics and clinical sequelae. Therefore, with regard to the multifaceted effects of BMP4 in regulating arterial wall remodeling, we hypothesize that BMP4 may play an important role in mediating the pathological responses of the venous wall to the arterial circulation. If our hypothesis is demonstrated correct, BMP4 inhibition could presumably serve as a novel strategy for preventing vein graft failure in coronary revascularization.