Abstract P135: Specialized Pro-resolving Molecular Pathway Is Impaired In Resistance Arteries From Hypertensive Rats.

Abstract

Specialized pro-resolving mediators (SPMs), derived from essential fatty acids, are known to playa major role in the immune system, as immunoresolvents. SPMs reduce acute inflammatoryresponses and leads to the clearance of pathogens and dying cells. Although we have demonstratedthat lipoxin A4, biosynthesized from the 5-lipoxygenase (LOX-5), improved endothelium-dependent relaxation in resistance arteries from SHR, it is unknown if (1) SPMs molecularpathways are present in resistance arteries independent of immune system activation, and (2)whether this pathway is dysfunctional in SHR. We hypothesized that the synthesis and downstreamsignaling of LOX-5-derived SPMs are impaired in resistance arteries from SHR. Mesentericresistance arteries (MRA) from male SHR (14-weeks old, n=5) and Wistar Kyoto (WKY) (14-weeks old, n=4) were collected to assess protein expression using Western blotting analysis. SHR`sMRA showed an increase in COX-2 expression (400%) when compared to WKY (p<0.05),demonstrating an inflammatory state. However, there was a reduction in the total LOX-5expression (30%) (Fig.1). Interestingly, an 65% increase in phosphorylation of 5-LOX at Ser 271was observed in MRA from SHR (Fig. 1) Ser 271 is responsible for the pro-inflammatory effectsof LOX-5, leading to a reduction of lipoxin A4, but an increase in the synthesis of leukotrienes.Supporting our previous data, we observed that formyl peptide receptor, a receptor that recognizesSPMs, was 30% decreased in arteries from in SHR. Together, these data show that vascular tissuepresents with the “machinery” to synthesize SPMs, and the resolution of inflammation“machinery” is impaired in hypertension.