The lymphatic vasculature is a blind-ended network crucial for tissue fluid homeostasis, immune surveillance and lipid absorption from the gut. Recent evidence has proposed an entirely venous-derived mammalian lymphatic system. In contrast, we reveal here that cardiac lymphatic vessels have a heterogeneous cellular origin, whereby formation of at least part of the cardiac lymphatic network is independent of sprouting from veins. Multiple cre-lox based lineage tracing revealed a potential contribution from the hemogenic endothelium during development and discrete lymphatic endothelial progenitor populations were confirmed by conditional knockout of Prox1 in Tie2+ and Vav1+ compartments. In the adult heart, myocardial infarction (MI) promoted a significant lymphangiogenic response, which was augmented by treatment with VEGF-C resulting in improved cardiac function. These data prompt the re-evaluation of a century-long debate on the origin of lymphatic vessels and suggest that lymphangiogenesis may represent a therapeutic target to promote cardiac repair following injury.

From historical studies of developing chick hearts to recent advances in regenerative injury models, the epicardium has arisen as a key player in heart genesis and repair. The epicardium provides paracrine signals to nurture growth of the developing heart from mid-gestation, and epicardium-derived cells act as progenitors of numerous cardiac cell types. Interference with either process is terminal for heart development and embryogenesis. In adulthood, the dormant epicardium reinstates an embryonic gene programme in response to injury. Furthermore, injury-induced epicardial signalling is essential for heart regeneration in zebrafish. Given these critical roles in development, injury response and heart regeneration, the application of epicardial signals following adult heart injury could offer therapeutic strategies for the treatment of ischaemic heart disease and heart failure.

Epicardium-derived cells (EPDCs) contribute cardiovascular cell types during development and in adulthood respond to Thymosin β4 (Tβ4) and myocardial infarction (MI) by reactivating a fetal gene programme to promote neovascularization and cardiomyogenesis. The mechanism for epicardial gene (re-)activation remains elusive. Here we reveal that BRG1, the essential ATPase subunit of the SWI/SNF chromatin–remodelling complex, is required for expression of Wilms’ tumour 1 (Wt1), fetal EPDC activation and subsequent differentiation into coronary smooth muscle, and restores Wt1 activity upon MI. BRG1 physically interacts with Tβ4 and is recruited by CCAAT/enhancer-binding protein β (C/EBPβ) to discrete regulatory elements in the Wt1 locus. BRG1-Tβ4 co-operative binding promotes optimal transcription of Wt1 as the master regulator of embryonic EPDCs. Moreover, chromatin immunoprecipitation-sequencing reveals BRG1 binding at further key loci suggesting SWI/SNF activity across the fetal epicardial gene programme. These findings reveal essential functions for chromatin–remodelling in the activation of EPDCs during cardiovascular development and repair.

ObjectiveThe study aims were (1) to identify the community prevalence of moderate or greater mitral or tricuspid regurgitation (MR/TR), (2) to compare subjects identified by population screening with those with known valvular heart disease (VHD), (3) to understand the mechanisms of MR/TR and (4) to assess the rate of valve intervention and long-term outcome.MethodsAdults aged ≥65 years registered at seven family medicine practices in Oxfordshire, UK were screened for inclusion (n=9504). Subjects with known VHD were identified from hospital records and those without VHD invited to undergo transthoracic echocardiography (TTE) within the Oxford Valvular Heart Disease Population Study (OxVALVE). The study population ultimately comprised 4755 subjects. The severity and aetiology of MR and TR were assessed by integrated comprehensive TTE assessment.ResultsThe prevalence of moderate or greater MR and TR was 3.5% (95% CI 3.1 to 3.8) and 2.6% (95% CI 2.3 to 2.9), respectively. Primary MR was the most common aetiology (124/203, 61.1%). Almost half of cases were newly diagnosed by screening: MR 98/203 (48.3%), TR 69/155 (44.5%). Subjects diagnosed by screening were less symptomatic, more likely to have primary MR and had a lower incidence of aortic valve disease. Surgical intervention was undertaken in six subjects (2.4%) over a median follow-up of 64 months. Five-year survival was 79.8% in subjects with isolated MR, 84.8% in those with isolated TR, and 59.4% in those with combined MR and TR (p=0.0005).ConclusionsModerate or greater MR/TR is common, age-dependent and is underdiagnosed. Current rates of valve intervention are extremely low.

An analysis of CSA, FSC, and SFI audit conditions was conducted identifying areas requiring operational changes to obtain certification. Audit reports for each standard differed in both number and focus of requirements. The FSC audits required more changes in environmental, social and economic themes, while CSA and SFI audit reports emphasized changes in management systems and aquatic ecosystems management. Although not a guarantee of changes in operations and management, the audit conditions point towards areas where forest certification can potentially have impacts on forest management.Key words: forest certification, standards, audit conditions, forest management