IL-11 is a crucial determinant of cardiovascular fibrosis.

Fibrosis is a common pathology in cardiovascular disease. In the heart, fibrosis causes mechanical and electrical dysfunction and in the kidney, it predicts the onset of renal failure. Transforming growth factor ß1 (TGFß1) is the principal pro-fibrotic factor, but its inhibition is associated with side effects due to its pleiotropic roles. We hypothesized that downstream effectors of TGFß1 in fibroblasts could be attractive therapeutic targets and lack upstream toxicity. Here we show, using integrated imaging-genomics analyses of primary human fibroblasts, that upregulation of interleukin-11 (IL-11) is the dominant transcriptional response to TGFß1 exposure and required for its pro-fibrotic effect. IL-11 and its receptor (IL11RA) are expressed specifically in fibroblasts, in which they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il-11 injection causes heart and kidney fibrosis and organ failure, whereas genetic deletion of Il11ra1 protects against disease. Therefore, inhibition of IL-11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli. These results reveal a central role of IL-11 in fibrosis and we propose that inhibition of IL-11 is a potential therapeutic strategy to treat fibrotic diseases.

Does preoperative statin therapy prevent postoperative atrial fibrillation in patients undergoing cardiac surgery?

A best evidence topic was written according to a structured protocol. The question addressed was: does preoperative statin therapy prevent postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery? There were 445 papers found using the reported search. From these, 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This paper includes three systematic reviews with meta-analysis, five randomized controlled trials and four retrospective studies. All the papers compared either all or some of the following postoperative complications: mortality, morbidity, AF, length of hospital stay (intensive care unit and hospital) and inflammatory markers. The largest study in this paper includes a systematic review of 91 491 patients that showed a reduction in postoperative AF with preoperative statin therapy (OR = 0.71, 95% CI 0.61-0.82, P <0.0001). However, the durations (3 days to 2 months preoperatively), doses and types of preoperative statin differed between these papers. Although the majority of studies (10 of 12) support the use of statins preoperatively, 2 studies found no association between preoperative statin therapy and the reduction of postoperative AF. In conclusion, the available evidence suggests that preoperative statin therapy in patients undergoing elective cardiac surgery is associated with the following: (1) a lower incidence and risk of developing postoperative AF, (2) reduced stroke, (3) a shorter hospital stay and (4) reduced levels of inflammatory markers postoperatively. However, while the evidence supports the use of statins preoperatively, the optimal duration, dose and type of statin cannot be concluded from this review.