Interventions in Wnt signaling as a novel therapeutic approach to improve myocardial infarct healing

Cardiovascular diseases (CVDs) are the leading causes of mortality worldwide. More people die from CVDs than from any other disease. According to WHO, 17.3 million people died from CVDs in 2008, representing 30% of all global deaths. Of these deaths, 7.3 million were due to coronary heart disease [1].Myocardial infarction (MI) is the result of an occlusion of a coronary artery, caused by a thrombus or an atheromatous ruptured plaque, which deprives the myocardium from sufficient blood flow. This leads to ischemia and eventually death of cardiomyocytes [2]. The location and duration of the occlusion is determinant for the outcome. However, during the last decades, more patients enter the wound-healing phase due to improvements in antithrombolytic and antiarrhythmic therapy.Wound healing is a complex process of consecutive cascades involving several cell types, and finalizes with scar formation. The first phase begins when necrotic cardiomyocytes trigger an inflammatory response by activation of the complement cascade [3]. In humans, the primary inflammatory phase occurs within 12 to 16？hours after MI and mainly attracts polymorphonuclear leukocytes (PMNLs) into the infarcted area. Peak numbers of PMNLs are observed at 24 to 48？hours after infarction. These cells partly remove the cellular debris by phagocytosis and attract lymphocytes, which in turn causes infiltration of macrophages that help to remove the dead cardiomyocytes [2,4]. The infiltrated inflammatory cells not only clear dead cells by phagocytosis but also release proteolytic enzymes and reactive oxygen species, which lead to additional cardiomyocyte death [5]. The second phase is defined by deposition of granulation tissue and starts two to three days after infarction. Here, new extracellular matrix (ECM) proteins are being deposited, starting from the border zone, and progressing into the central area of the infarct later on. Anti-inflammatory cytokines such as transforming growth factor (TGF)-β1, relea