MicroRNAs in mesenteric lymph and plasma during acute pancreatitis.

OBJECTIVE: To isolate microRNAs (miRNAs) from mesenteric lymph (ML) and peripheral blood and identify those that change with experimental acute pancreatitis (AP). To assess identified AP-associated miRNAs in patient plasma to evaluate them as clinical biomarkers of AP. BACKGROUND: miRNAs, small non-protein-coding molecules that regulate gene expression, are present in many biological fluids. They are increasingly interesting as biomarkers of disease and as novel signaling molecules in pathogenesis. METHODS: Affymetrix miRNA profiling was performed on ML collected from 3 groups of rats with either mild or moderate taurocholate-induced AP and sham controls. Quantitative reverse transcription-polymerase chain reaction was used to validate selected miRNAs in matched rat lymph and plasma and then measured in patients with mild or moderate AP and in healthy volunteers. RESULTS: Eighty-five miRNAs were detectable in rat ML, and many were abundant in all animals irrespective of the presence of AP. Seven miRNAs, comprising miR-375, -217, -148a, -216a, -122, -214, and -138, were increased in ML from rats with AP (P < 0.01). Their abundance also altered with disease severity. miRNAs miR-217, -375, -122, and -148a were also increased in matched rat plasma samples by quantitative reverse transcription-polymerase chain reaction. In the clinical studies, plasma miR-216a was significantly increased in both mild and moderate AP. CONCLUSIONS: This study is the first to demonstrate both the presence of circulating miRNAs in lymph and the alteration of specific miRNAs in AP. Furthermore, these miRNAs alter in rat and human AP plasma and have potential to be explored as novel biomarkers of pancreatitis.

Acute pancreatitis conditioned mesenteric lymph causes cardiac dysfunction in rats independent of hypotension.

BACKGROUND: Critical illness including severe acute pancreatitis is associated with the multiple organ dysfunction syndrome. The "gut-lymph" hypothesis states that multiple organ dysfunction syndrome is due to release of toxic factors from the intestine into the mesenteric lymph. The aims of this study were to determine the effect of normotensive acute pancreatitis conditioned mesenteric lymph on cardiac function and whether external drainage of mesenteric lymph would protect the heart. METHODS: Groups of normal rats and those with normotensive taurocholate induced acute pancreatitis, had either no lymphatic intervention or thoracic duct ligation and external drainage of mesenteric lymph. After 6 hours, the hearts were removed for ex vivo functional measurements, including cardiac output, ventricular contractility (+dP/dt), and relaxation (-dP/dt). In a second experiment, mesenteric lymph from normal rats and those with established acute pancreatitis was infused into ex vivo perfused normal working rat hearts to assess impact on cardiac function. Heart and lung tissues were collected for assessment of edema. RESULTS: Significant cardiac dysfunction, denoted by decreased cardiac output (21%), contractility (37%), relaxability (23%), and increased cardiac tissue edema (2-fold), developed in rats with established acute pancreatitis and no lymphatic intervention compared with the control group (all P < .05). Strikingly this cardiac dysfunction and edema was normalized in acute pancreatitis rats that had undergone prior thoracic duct ligation and external drainage of mesenteric lymph. In the second experiment, infusion of acute pancreatitis conditioned mesenteric lymph resulted in an immediate and significant similar magnitude decrease in of cardiac output (17%), contractility (22%), and relaxation (27%) compared with the infusion of normal lymph (all P <.05). CONCLUSION: Mesenteric lymph from normotensive acute pancreatitis animals caused significant cardiac dysfunction which could be prevented by thoracic duct ligation and external drainage of mesenteric lymph.