Abstract 423: Potential Role of Natriuretic Peptides in Atherosclerosis and Inflammation

Abstract

Background: Brain natriuretic peptide (BNP) is currently recognized as one of the important markers of Congestive heart failure (CHF). BNP levels are simple and objective measures of cardiac function in patients with ischemic injury. These measurements can be used to diagnose HF, including diastolic dysfunction and inflammation. Plasma levels of BNP and ANP are elevated in CHF, especially after myocardial infarction (MI). Furthermore, within the heart tissue, gene expression of BNP and ANP is reportedly up-regulated in animal models with MI and CHF, and in human heart disease. In this study, we tested the natriuretic peptides ability in reduction of peroxides as well as inflammation Methods: BNP and ANP were commercially synthesized and their ability to reduce lipid peroxides (LOOH) was measured using 13-hydroperoxyoctadecadienoic acid (13-HPODE). Low density lipoprotein (LDL) was isolated from human plasma and its oxidation was performed using copper in the presence or absence of the peptides. The ability of these peptides to neutralize charges of modified lipoproteins, as well as attenuate inflammation, were analyzed. Oxidized LDL (Ox-LDL)/Ac-LDL was pretreated with increasing concentrations of peptides to evaluate charge neutralizing properties of the peptides. RAW cells were incubated with LPS pretreated with peptides. RNA was isolated from treated cells and real time PCR was performed using mouse IL-1α and IL-6 primers. Results: Natriuretic peptides reduced 13-HPODE and inhibited the oxidation of LDL. Reduced IL-1α and IL-6 gene expression was observed in the presence of LPS. Conclusion: The results of our studies suggest that these peptides a) inhibit the oxidation of LDL and b) have an inhibitory effect on inflammatory cytokine/gene production in the presence of LPS. Based on these results, we predict that natriuretic peptides could have therapeutic potential in reducing CVD/atherosclerosis-associated inflammation.