Attenuation of monocyte chemotaxis--a novel anti-inflammatory mechanism of action for the cardio-protective hormone B-type natriuretic peptide

B-type natriuretic peptide (BNP) is a prognostic and diagnostic marker for heart failure (HF). An anti-inflammatory, cardio-protective role for BNP was proposed. In cardiovascular diseases including pressure overload-induced HF, perivascular inflammation and cardiac fibrosis are, in part, mediated by monocyte chemoattractant protein (MCP)1-driven monocyte migration. We aimed to determine the role of BNP in monocyte motility to MCP1. A functional BNP receptor, natriuretic peptide receptor-A (NPRA) was identified in human monocytes. BNP treatment inhibited MCP1-induced THP1 (monocytic leukemia cells) and primary monocyte chemotaxis (70 and 50 %, respectively). BNP did not interfere with MCP1 receptor expression or with calcium. BNP inhibited activation of the cytoskeletal protein RhoA in MCP1-stimulated THP1 (70 %). Finally, BNP failed to inhibit MCP1-directed motility of monocytes from patients with hypertension (n = 10) and HF (n = 6) suggesting attenuation of this anti-inflammatory mechanism in chronic heart disease. We provide novel evidence for a direct role of BNP/NPRA in opposing human monocyte migration and support a role for BNP as a cardio-protective hormone up-regulated as part of an adaptive compensatory response to combat excess inflammation.

Lifestyle Risk Factors for Serrated Colorectal Polyps: a Systematic Review and Meta-Analysis

Background & Aims: Certain subsets of colorectal serrated polyps (SP) have malignant potential. Weperformed a systematic review and meta-analysis to investigate the association between modifiablelifestyle factors and risk for SPs. 
Methods: We conducted a systematic search of Medline, Embase, and Web of Science, forobservational or interventional studies that contained the terms risk or risk factor, and serrated orhyperplastic, and polyps or adenomas, and colorectal (or synonymous terms), published by March2016. Titles and abstracts of identified articles were independently reviewed by at least 2 reviewers.Adjusted relative risks (RR) and 95% CIs were combined using random effects meta-analyses toassess the risk of SP, when possible. 
Results: We identified 43 studies of SP risk associated with 7 different lifestyle factors: smoking,alcohol, body fatness, diet, physical activity, medication and/or hormone replacement therapy.When we compared the highest and lowest categories of exposure, factors we found to significantlyincrease risk for SP included tobacco smoking (RR, 2.47; 95% CI, 2.12–2.87), alcohol intake (RR, 1.33;95% CI, 1.17–1.52), body mass index (RR, 1.40; 95% CI, 1.22–1.61), and high intake of fat or meat.Direct associations for smoking and alcohol, but not body fat, tended to be stronger for sessileserrated adenomas/polyps than hyperplastic polyps. In contrast, factors we found to significantlydecrease risks for SP included use of non-steroidal anti-inflammatory drugs (RR, 0.77; 95% CI, 0.65–0.92) or aspirin (RR, 0.81; 95% CI, 0.67–0.99), as well as high intake of folate, calcium, or fiber. Nosignificant associations were detected between SP risk and physical activity or hormone replacementtherapy. 
Conclusions: Several lifestyle factors, most notably smoking and alcohol, are associated with SP risk.These findings enhance our understanding of mechanisms of SP development and indicate that riskof serrated pathway colorectal neoplasms could be reduced with lifestyle changes.

Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas, and hyperplastic polyps

Objective: To identify modifiable factors associated with sessile serrated polyps (SSPs), and compare the association of these factors to conventional adenomas (ADs) and hyperplastic polyps (HPs). Design: We utilized data from the Tennessee Colorectal Polyp Study, a colonoscopy-based case-control study. Included were 214 SSP cases, 1779 AD cases, 560 HP cases and 3851 polyp-free controls. Results: Cigarette smoking was associated with increased risk for all polyps and was stronger for SSPs than for ADs (OR 1.74. 95% CI: 1.16-2.62, for current vs. never, ptrend=0.008). Current regular use of nonsteroidal anti-inflammatories (NSAID) was associated with a 40% reduction in SSPs risk in comparison to never-users (OR 0.68, 95% CI 0.48-0.96, ptrend=0.03), similar to the association with AD. Red meat intake was strongly associated with SSPs risk (OR 2.59, 95% CI 1.41-4.74 for highest vs. lowest intake, ptrend<0.001) and the association with SSP was stronger than with AD (ptrend=0.003). Obesity, folate intake, fiber intake, and fat intake were not associated with SSP risk after adjustment for other factors. Exercise, alcohol use, and calcium intake were not associated with risk for SSPs. Conclusion: SSPs share some modifiable risk factors for ADs, some of which are more strongly associated with SSPs than ADs. Thus, preventive efforts to reduce risk for ADs may also be applicable to SSPs. Additionally, SSPs have some distinctive risk factors. Future studies should evaluate the preventive strategies for these factors. The findings from this study also contribute to an understanding of the etiology and biology of SSPs.