Human neutrophil peptides: a novel potential mediator of inflammatory cardiovascular diseases

1 The Keenan Research Centre in the Li Ka Shing Knowledge Institute of Saint Michael's Hospital; and 2 Departments of Anaesthesia and Physiology, 3 Cardiovascular Sciences Collaborative Program, 4 Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada ABSTRACT The traditional view of atherosclerosis has recently been expanded from a predominantly lipid retentive disease to a coupling of inflammatory mechanisms and dyslipidemia. Studies have suggested a novel role for polymorphonuclear neutrophil (PMN)-dominant inflammation in the development of atherosclerosis. Human neutrophil peptides (HNPs), also known as -defensins, are secreted and released from PMN granules upon activation and are conventionally involved in microbial killing. Current evidence suggests an important immunomodulative role for these peptides. HNP levels are markedly increased in inflammatory diseases including sepsis and acute coronary syndromes. They have been found within the intima of human atherosclerotic arteries, and their deposition in the skin correlates with the severity of coronary artery diseases. HNPs form complexes with LDL in solution and increase LDL binding to the endothelial surface. HNPs have also been shown to contribute to endothelial dysfunction, lipid metabolism disorder, and the inhibition of fibrinolysis. Given the emerging relationship between PMN-dominant inflammation and atherosclerosis, HNPs may serve as a link between them and as a biological marker and potential therapeutic target in cardiovascular diseases including coronary artery diseases and acute coronary syndromes. -defensins; inflammation; cytokine Address for reprint requests and other correspondence: H. Zhang, Rm. 7-007, Queen Wing, 30 Bond St., Toronto, ON M5B 1W8, Canada (e-mail: zhangh{at}smh.toronto.on.ca )