First-in-Man Use of the Percutaneous 10F Reitan Catheter Pump for Cardiorenal Syndrome.

Cardiorenal syndrome worsens outcome in patients with decompensated chronic heart failure, and complicates recompensation by medical therapy. Mechanical circulatory support has the potential to improve renal function, and likely mitigates diuretic resistance in patients with severe cardiorenal syndrome. The Reitan catheter pump (RCP) is a novel temporary percutaneous circulatory support system for reducing cardiac afterload and increasing renal preload. Here, we report on the first-in-man use of the 10F-version of the RCP device, which was associated with favorable effects on hemodynamics and diuresis. Further investigation to evaluate safety and efficacy of this promising approach is warranted.

Happy heart syndrome: role of positive emotional stress in takotsubo syndrome.

AIMS: Takotsubo syndrome (TTS) is typically provoked by negative stressors such as grief, anger, or fear leading to the popular term 'broken heart syndrome'. However, the role of positive emotions triggering TTS remains unclear. The aim of the present study was to analyse the prevalence and characteristics of patients with TTS following pleasant events, which are distinct from the stressful or undesirable episodes commonly triggering TTS. METHODS AND RESULTS: Takotsubo syndrome patients with preceding pleasant events were compared to those with negative emotional triggers from the International Takotsubo Registry. Of 1750 TTS patients, we identified a total of 485 with a definite emotional trigger. Of these, 4.1% (n = 20) presented with pleasant preceding events and 95.9% (n = 465) with unequivocal negative emotional events associated with TTS. Interestingly, clinical presentation of patients with 'happy heart syndrome' was similar to those with the 'broken heart syndrome' including symptoms such as chest pain [89.5% (17/19) vs. 90.2% (412/457), P = 1.0]. Similarly, electrocardiographic parameters, laboratory findings, and 1-year outcome did not differ. However, in a post hoc analysis, a disproportionate higher prevalence of midventricular involvement was noted in 'happy hearts' compared with 'broken hearts' (35.0 vs. 16.3%, P = 0.030). CONCLUSION: Our data illustrate that TTS can be triggered by not only negative but also positive life events. While patient characteristics were similar between groups, the midventricular TTS type was more prevalent among the 'happy hearts' than among the 'broken hearts'. Presumably, despite their distinct nature, happy and sad life events may share similar final common emotional pathways, which can ultimately trigger TTS.

Vascular importance of the miR-212/132 cluster.

RATIONALE: Many processes in endothelial cells including angiogenic responses are regulated by microRNAs. However, there is limited information available about their complex cross-talk in regulating certain endothelial functions. AIM: The objective of this study is to identify endothelial functions of the pro-hypertrophic miR-212/132 cluster and its cross-talk with other microRNAs during development and disease. METHODS AND RESULTS: We here show that anti-angiogenic stimulation by transforming growth factor-beta activates the microRNA-212/132 cluster by derepression of their transcriptional co-activator cAMP response element-binding protein (CREB)-binding protein (CBP) which is a novel target of a previously identified pro-angiogenic miRNA miR-30a-3p in endothelial cells. Surprisingly, despite having the same seed-sequence, miR-212 and miR-132 exerted differential effects on endothelial transcriptome regulation and cellular functions with stronger endothelial inhibitory effects caused by miR-212. These differences could be attributed to additional auxiliary binding of miR-212 to its targets. In vivo, deletion of the miR-212/132 cluster increased endothelial vasodilatory function, improved angiogenic responses during postnatal development and in adult mice. CONCLUSION: Our results identify (i) a novel miRNA-cross-talk involving miR-30a-3p and miR-212, which led to suppression of important endothelial genes such as GAB1 and SIRT1 finally culminating in impaired endothelial function; and (ii) microRNAs may have different biological roles despite having the same seed sequence.

A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction.

AIMS: Takotsubo cardiomyopathy (TTC) remains a potentially life-threatening disease, which is clinically indistinguishable from acute myocardial infarction (MI). Today, no established biomarkers are available for the early diagnosis of TTC and differentiation from MI. MicroRNAs (miRNAs/miRs) emerge as promising sensitive and specific biomarkers for cardiovascular disease. Thus, we sought to identify circulating miRNAs suitable for diagnosis of acute TTC and for distinguishing TTC from acute MI. METHODS AND RESULTS: After miRNA profiling, eight miRNAs were selected for verification by real-time quantitative reverse transcription polymerase chain reaction in patients with TTC (n = 36), ST-segment elevation acute myocardial infarction (STEMI, n = 27), and healthy controls (n = 28). We quantitatively confirmed up-regulation of miR-16 and miR-26a in patients with TTC compared with healthy subjects (both, P < 0.001), and up-regulation of miR-16, miR-26a, and let-7f compared with STEMI patients (P < 0.0001, P < 0.05, and P < 0.05, respectively). Consistent with previous publications, cardiac specific miR-1 and miR-133a were up-regulated in STEMI patients compared with healthy controls (both, P < 0.0001). Moreover, miR-133a was substantially increased in patients with STEMI compared with TTC (P < 0.05). A unique signature comprising miR-1, miR-16, miR-26a, and miR-133a differentiated TTC from healthy subjects [area under the curve (AUC) 0.835, 95% CI 0.733-0.937, P < 0.0001] and from STEMI patients (AUC 0.881, 95% CI 0.793-0.968, P < 0.0001). This signature yielded a sensitivity of 74.19% and a specificity of 78.57% for TTC vs. healthy subjects, and a sensitivity of 96.77% and a specificity of 70.37% for TTC vs. STEMI patients. Additionally, we noticed a decrease of the endothelin-1 (ET-1)-regulating miRNA-125a-5p in parallel with a robust increase of ET-1 plasma levels in TTC compared with healthy subjects (P < 0.05). CONCLUSION: The present study for the first time describes a signature of four circulating miRNAs as a robust biomarker to distinguish TTC from STEMI patients. The significant up-regulation of these stress- and depression-related miRNAs suggests a close connection of TTC with neuropsychiatric disorders. Moreover, decreased levels of miRNA125a-5p as well as increased plasma levels of its target ET-1 are in line with the microvascular spasm hypothesis of the TTC pathomechanism.

Ex vivo expanded haematopoietic progenitor cells improve dermal wound healing by paracrine mechanisms.

BACKGROUND: Although dermal wounds are common, treatment remains limited and largely ineffective. Recent studies suggest that therapeutic application of progenitor cells is useful for tissue regeneration. OBJECTIVE: We here investigated the effects exerted by the recently characterized immortalized haematopoietic progenitor cell line DKmix and their conditioned medium in a murine wound healing model. METHODS AND RESULTS: Injection of both DKmix cells and their conditioned medium accelerated wound repair between days 3 and 10 compared with PBS-injected control mice (n = 8, P < 0.01 DKmix cells vs control, P < 0.01 conditioned medium vs control at day 6). The treated groups exhibited more CD31(+)-capillaries at day 6 after injury compared with the control group (n = 4, P < 0.01 DKmix cells vs control, P < 0.001 conditioned medium vs control), whereas there was no change in infiltrated CD68(+) macrophages. Conditioned medium of DKmix cells induced tube formation of human endothelial cells in Matrigel assays (n = 4-6, P < 0.05 conditioned medium vs control) as well as migration (n = 4, P < 0.01 conditioned medium vs control) and proliferation of murine 3T3 fibroblasts (n = 5, P < 0.05 conditioned medium vs control). Abundant levels of matrix metalloproteinase -2 and -9 in the supernatants were detected. Protein arrays of the supernatants revealed a strong secretion of cytokines and growth factors, such as monocyte chemoatractant protein-1 and GM-CSF from DKmix cells. CONCLUSION: DKmix cells improve skin-substitute wound healing by promoting angiogenesis as well as migration and proliferation of fibroblasts. These data suggest that immortalized haematopoietic progenitor cells significantly improve dermal wound healing by paracrine effects.