“
“Background: Galectin-3 (Gal-3) shows the ability of survival prediction in heart failure (HF) patients. However, Gal-3 is strongly associated with serum markers of cardiac extracellular matrix (ECM) turnover. The aim of this study is to compare the impact of Gal-3 and serum markers of cardiac ECM turnover on prognostic prediction of chronic systolic HF patients. Methods: Serum Gal-3, brain natriuretic peptide (BNP), extracellular matrix including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2,

9 (MMP-2, 9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed. Cox regression analysis was used for survival analysis. Results: A total of 105 (81 male) patients were enrolled. During 980 +/- 346 days follow-up, 17 patients died and 36 episodes of HF Thiazovivin admission happened. Mortality of these patients

was significantly associated with the log PIIINP (beta= 15.380; P=0.042), log TIMP-1(beta= 44.530; P=0.003), HDAC assay log MMP-2 (beta= 554.336; P smaller than 0.001), log BNP (beta= 28.273; P=0.034). Log Gal-3 (beta= 7.484; P=0.066) is borderline associated with mortality. Mortality or first HF admission of these patients was significantly associated with the log TIMP-1(beta= 16.496; P=0.006), log MMP-2 (beta= 221.864; P smaller than 0.001), log BNP (beta= 5.999; P=0.034). Log Gal-3 (beta= 4.486; P=0.095) only showed borderline significance. In several models adjusting clinical parameters, log MMP-2 was significantly associated

with clinical outcome. In contrast, log Gal-3 was not. Conclusion: The prognostic strength of MMP-2 to clinical outcome prediction in HF patients is stronger than Gal-3.”
“Objective-The present studies aimed a elucidating the role of prostaglandin E-2 receptor subtype 3 (E-prostanoid [EP] 3) in regulating blood pressure.\n\nMethods and Results-Mice bearing a genetic disruption of the EP3 gene (EP3-/-) exhibited reduced baseline mean arterial pressure monitored by both tail-cuff and carotid arterial catheterization. The pressor responses induced Nepicastat chemical structure by EP3 agonists M&B28767 and sulprostone were markedly attenuated in EP3(-/-) mice, whereas the reduction of blood pressure induced by prostaglandin E-2 was comparable in both genotypes. Vasopressor effect of acme or chronic infusion of angiotensin II (Ang II) was attenuated in EP3(-/-) mice. Ang II-induced vasoconstriction in mesenteric arteries decreased in EP3(-/-) group. In mesenteric arteries from wild-type mice, Ang II-induced vasoconstriction was inhibited by EP3 selective antagonist DG-041 or L798106. The expression of Arhgef-1 is attenuated in EP3 deficient mesenteric arteries. EP3 antagonist DG-041 diminished Ang II-induced phosphorylation of myosin light chain 20 and myosin phosphatase target subunit 1 in isolated mesenteric arteries.