Abstract
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 expression 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 (highfat-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 immunoregulatory 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 responding to exogenous danger-signals, and act within the context of a myocardial “first-line-of-defense”.
Highlights
Defensins are small cationic host defense peptides (HDPs) with a broad functional repertoire that position them as central players within the context of an innate immune response [1,2]
We found that an innate myocardial response that involves rBDs is activated by highfat-diet feeding in rats, and that these Host defense peptides (HDPs) influence monocyte migration-findings that suggest the peptides respond to exogenous danger-signals, and act within the context of a myocardial “first-line-of-defense”
RT-PCR products were subsequently assessed by gel electrophoresis, and identified as single bands of anticipated amplicon size. These findings suggest that known inflammatory mediators trigger an up-regulation of cardiac host defense peptides-likely contributing to an intrinsic molecular defense of the myocardium against danger signals
Summary
Defensins are small cationic host defense peptides (HDPs) with a broad functional repertoire that position them as central players within the context of an innate immune response [1,2]. Several studies have in recent years reported on pattern recognition receptors (TLRs), signaling pathways (NF B), as well as different effector molecules relevant to an innate immune response (e.g. cytokines and defensins) expressed intrinsically by the cardiovascular system, as previously reviewed [3]. These findings support that the heart is capable of establishing a local innate defense response, and as such is not solely positioned at the mercy of classical immune cells’ efficacy at fighting off pathogens and other injurious danger elements. The role played by certain lipoproteins in atherosclerotic CVD has been confirmed in clinical trials [19], and en-
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