Transforming growth factor β (TGF-β1) is a pleiotropic cytokine with many and complex effects in cell and tissue physiology. This is made possible by a very complex and interwoven signaling system, whose regulation continues to be the focus of a growing line of research. This complex regulation translates to a key role in cardiovascular physiology, hemostasis, and the blood–vessel interface. In accordance with this, the TGF-β1 pathway appears to be deregulated in related disorders, such as atherosclerotic vascular disease and myeloproliferative syndromes. It is expected that the growing amount of experimental and clinical research will yield medical advances in the applications of knowledge of the TGF-β1 pathway to diagnosis and therapeutics.

Abstract. We report the results of a laboratory study of the aestivation of Hormogaster elisae to determine the nature of the inactive period (diapause or quiescence) and to evaluate the influence of soil moisture, temperature, season, and earthworm body weight on the process. The results showed that specimens of H. elisae underwent facultative diapause—paradiapause—characterized by the construction of aestivation chambers in which the animal coils up and its activity decreases. Soil moisture appeared to be the most important environmental factor involved in the onset of aestivation. Temperature and time of year also had some influence, but earthworm body weight appeared to have none. Aestivating earthworms showed a decrease of 41.6% in mean body weight. Once replaced in soil with 20% moisture content, they took 6.4±3.1 d to exit their chambers and another 6.5±3.6 d to recover their initial body weight.

Aims/hypothesis Inflammation is a common feature in cardiovascular diseases, including diabetes mellitus. In addition to the well-known inflammatory role of cyclooxygenase-2 (COX-2), this protein has also been implicated in apoptosis resistance in tumour cells. Vascular smooth muscle cells (VSMC) from diabetic patients are also resistant to apoptosis because of an increased abundance of B cell lymphoma 2 protein (BCL2). In this work, we investigated whether overproduction of COX-2 was involved in the resistance to apoptosis in VSMC from diabetic patients. Methods VSMC were obtained from internal mammary arteries from patients who had undergone coronary artery bypass graft surgery. Apoptosis was measured by DNA fragmentation, BCL2 degradation and cytochrome c release.Results Apoptosis induced by C-reactive protein in cells from non-diabetic patients was mediated by COX-2. VSMC from diabetic patients showed higher basal levels of COX-2 compared with those from non-diabetic patients. Transfection of VSMC from non-diabetic patients with a plasmid containing COX-2 (also known as PTGS2) increased basal production of COX-2 and BCL2 and mimicked the resistance to apoptosis that occurs in diabetic patients. We also found a significant correlation (R=0.846, p=0.016) between COX-2 and BCL2 production in arterial rings from diabetic patients measured by confocal microscopy. However, inhibition of COX-2 production by small interfering RNA proved unable to reverse BCL2 production in diabetic VSMC. Conclusions/interpretation These results suggest a link between inflammation (COX-2) and apoptosis resistance (BCL2) in the arteries of diabetic patients. This relationship is not causative and the common production of these two proteins may be co-regulated by shared regulatory elements in diabetes.

Dabigatran is an emerging oral anticoagulant which is a direct inhibitor of thrombin activity. It has been approved in the European Union and the United States of America for the prevention of thrombosis after major orthopedic surgery. It has also been approved by the American Food and Drug Administration and the European Medicines Agency for the prevention of stroke in chronic atrial fibrillation. Dabigatran provides a stable anticoagulation effect without any need to perform periodical laboratory controls. Of note, there is a growing amount of clinical evidence which shows its safety and efficacy. For these reasons, dabigatran may suppose a revolution in oral anticoagulation. However, two important limitations remain. First, it is contraindicated in patients with end-stage renal disease. Second, there is no evidence of the prevention of thrombosis in mechanical heart valves.

BackgroundTransforming growth factor beta (TGF-β1) is a pleiotropic cytokine, which is deregulated in atherosclerosis; however the role of age in this process is unknown. We aimed to assess whether TGF-β1 signaling is affected by age.MethodsVascular smooth muscle cells (VSMC) were obtained from patients undergoing abdominal surgery. Levels of TGF-β1 were measured by ELISA in sera from 169 patients undergoing coronary artery bypass grafting (CABG). The p27 expression was determined by Western blot from internal mammary arteries (IMA) obtained from CABG patients (n = 13). In VSMC from these patients undergoing abdominal surgery, secretion of TGF-β1 was determined by ELISA of cell-conditioned media.ResultsIn VSMC from aged patients we observed a lower TGF-β1 secretion, measured as TGF-β1 concentration in cell conditioned medium (p < 0.001). This effect was correlated to an age-dependent decrease of p27 expression in IMA from aged CABG patients. In a similar manner, there was an age-dependent decrease of serum TGF-β1 levels in CABG patients (p = 0.0195).ConclusionsVSMC from aged patients showed a higher degree of cellular senescence and it was associated to a lower TGF-β1 secretion and signaling.

BackgroundWe aimed to test the antiproliferative effect of acetylsalicylic acid (ASA) on vascular smooth muscle cells (VSMC) from bypass surgery patients and the role of transforming growth factor beta 1 (TGF-β1).Methodology/Principal FindingsVSMC were isolated from remaining internal mammary artery from patients who underwent bypass surgery. Cell proliferation and DNA fragmentation were assessed by ELISA. Protein expression was assessed by Western blot. ASA inhibited BrdU incorporation at 2 mM. Anti-TGF-β1 was able to reverse this effect. ASA (2 mM) induced TGF-β1 secretion; however it was unable to induce Smad activation. ASA increased p38MAPK phosphorylation in a TGF-β1-independent manner. Anti-CD105 (endoglin) was unable to reverse the antiproliferative effect of ASA. Pre-surgical serum levels of TGF-β1 in patients who took at antiplatelet doses ASA were assessed by ELISA and remained unchanged.Conclusions/Significance In vitro antiproliferative effects of aspirin (at antiinflammatory concentration) on human VSMC obtained from bypass patients are mediated by TGF-β1 and p38MAPK. Pre-surgical serum levels of TGF- β1 from bypass patients who took aspirin at antiplatelet doses did not change.

BackgroundCardiovascular disease has been linked to endothelial progenitor cell (EPC) depletion and functional impairment in atherosclerosis and aortic stenosis. EPCs may play a pivotal role in vascular grafting. However, the EPC depletion in coronary artery bypass grafting (CABG) patients has not been compared to coronary artery disease-free valvular replacement patients with aortic stenosis.MethodsWe aimed to assess the basal number of CD34+/KDR+ and CD34+/CD144+ cells in CABG patients, compared to aortic stenosis valvular replacement patients. 100 patients (51 CABG and 49 valvular surgery ones) were included in the present study. All CABG or valvular patients had angiographic demonstration of the presence or the absence of coronary artery disease, respectively. Numbers of CD34+/KDR+ and CD34+/CD144+ were assessed by flow cytometry of pre-surgical blood samples.ResultsWe found a lower number of CD34+/CD144+ cells in CABG patients compared to valvular patients (0.21 ± 0.03% vs. 0.47 ± 0.08%), and this difference remained statistically significant after the P was adjusted for multiple comparisons (P = 0.01428). Both groups had more EPCs than healthy controls.ConclusionsPre-surgical CD34+/CD144+ numbers are decreased in CABG patients, compared to valvular patients with absence of coronary disease.

SummaryThis paper reports the composition and horizontal distribution of an earthworm community at El Molar (Madrid), and the underlying causes of its distribution. Five species of earthworms were found. The most abundant species were Hormogaster elisae, Allolobophora rosea and Allolobophora caliginosa trapezoides, which showed an aggregate-type distribution. Coarse sand, organic matter and nitrogen appear to be the factors with the greatest influence on H. elisae distribution, whereas porosity and aeration have influence on A. c. trapezoides, and clay, organic matter and nitrogen on the presence of A. rosea.