Inflammation plays a central role in development of cardiovascular pathology, and enhanced understanding of the innate immune response will help direct novel therapeutic strategies to address heart disease. Host defense peptides (HDPs)—hereunder defensins —exhibit antimicrobial, chemotactic, tissue healing and other key biological properties. Beta-defensin ex pression in whole-heart-homogenate has been reported in different species, and plasma alpha-defensins have been associated with cardiovascular morbidity and mortality. Still, the role of defensins in cardiac pathophysiology remains widely undetermined. Here, we show that a subset of rat-beta-defensins (rBDs) is constitutively expressed in the myocardium, and that their gene-expression level is influenced by systemic exposure to inflammatory mediators (high fat-diet and lipopolysaccharide). Using synthetic analogues of select rBD peptides, we evaluated the antimicrobial activity of these HDPs against clinically relevant pathogens and their ability as immunoregu latory compounds. We found that an innate myocardial response that involves rBDs is activated by highfat-diet feeding in rats, and that these HDPs influence monocyte migration- findings that suggest the peptides respond ing to exogenous danger-signals, and act with in the context of a myocardial “first-line-of-defense”.
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