Flow directionality, mountain barriers and functional traits determine diatom metacommunity structuring of high mountain streams.

Stream metacommunities are structured by a combination of local (environmental filtering) and regional (dispersal) processes. The unique characters of high mountain streams could potentially determine metacommunity structuring, which is currently poorly understood. Aiming at understanding how these characters influenced metacommunity structuring, we explored the relative importance of local environmental conditions and various dispersal processes, including through geographical (overland), topographical (across mountain barriers) and network (along flow direction) pathways in shaping benthic diatom communities. From a trait perspective, diatoms were categorized into high-profile, low-profile and motile guild to examine the roles of functional traits. Our results indicated that both environmental filtering and dispersal processes influenced metacommunity structuring, with dispersal contributing more than environmental processes. Among the three pathways, stream corridors were primary pathway. Deconstructive analysis suggested different responses to environmental and spatial factors for each of three ecological guilds. However, regardless of traits, dispersal among streams was limited by mountain barriers, while dispersal along stream was promoted by rushing flow in high mountain stream. Our results highlighted that directional processes had prevailing effects on metacommunity structuring in high mountain streams. Flow directionality, mountain barriers and ecological guilds contributed to a better understanding of the roles that mountains played in structuring metacommunity.

Extracardiac-Lodged Mesenchymal Stromal Cells Propel an Inflammatory Response Against Myocardial Infarction via Paracrine Effects.

Transplantation of stem cells, including mesenchymal stromal cells (MSCs), improves the recovery of cardiac function after myocardial infarction (MI) in experimental studies using animal models and in patients. However, the improvement of cardiac function following MSC transplantation remains suboptimal in both preclinical and clinical studies. Understanding the mechanism of cell therapy may improve its therapeutic outcomes, but the mode of action mediating stem cell promotion of cardiac repair is complex and not fully understood. Recent studies suggest that the immunomodulatory effects of MSCs on the macrophage M1/M2 subtype transition allow the transplanted stem cells to inhibit inflammation-induced injury and promote cardiac repair in acute MI. However, equally compelling evidence shows that there is poor survival and minimal graft persistence of transplanted MSCs within the infarcted heart tissues, negating the view that graft survival per se is required for the observed high rate and long duration of the transition from proinflammatory M1 to reparative M2 macrophages in the infarcted myocardium. Therefore, we raised a novel hypothesis that the therapeutic effects of MSC transplantation for acute MI depends not primarily on the grafted cells in infarct myocardium, but that MSCs migrating to and being lodged in the extracardiac organs, demonstrating good graft survival and persistence, may render the therapeutic effects in MI. More specifically, MSC transplantation promotes the transition from M1 to M2 in extracardiac organs, such as spleen and bone marrow, and therapeutic effects are conferred to the infarcted myocardium via paracrine effects. In MSC transplantation, the conversion from proinflammatory M1 to anti-inflammatory M2 monocytes may occur remotely from the heart and may serve as one of the major pathways in regulating the dual effects of inflammation. This hypothesis, if proven valid, may represent an important new mechanism of action to be considered for the future of MSC transplantation in the treatment of MI.

Comparison of restenosis rate with sirolimus-eluting stent in STEMI patients with and without diabetes at 6-month angiographic follow-up.

OBJECTIVE: Patients with diabetes mellitus (DM) are at high risk for restenosis after coronary stenting. However, whether drug-eluting stents are effective in diabetic patients presenting with ST-segment elevation myocardial infarction (STEMI) is uncertain. We report on a series of patients with or without DM followed up for 6 months after sirolimus-eluting stent implantation. METHODS: This cohort study enrolled 195 STEMI patients who underwent sirolimus-eluting stent implantation and accepted angiographic followup at 6 months. RESULTS: There were no significant differences between the two groups in baseline clinical characteristics and risk factors. The two groups were treated with similar stent lengths and diameters. The unadjusted in-stent restenosis was significantly higher in diabetic than in non-diabetic patients at 6 months (7.8 vs. 1.7, P < 0.05). Multivariate analysis showed that only diabetes and current smoking were independent predictors of restenosis (odds ratio 12.82 and 7.98, respectively, both P < 0.05). CONCLUSION: The present study demonstrated that diabetes increased restenosis after sirolimus-eluting stent placement in STEMI patients. This finding implicates that diabetes remains an important predictor for restenosis in the DES era.

Cardiac extracellular matrix tenascin-C deposition during fibronectin degradation.

Tenascin-C (TN-C) might aggravate left ventricular remodeling after myocardial infarction (MI). Our previous study demonstrated that ventricular remodeling after MI is linked with the degradation of fibronectin (FN). The aim of the present study was to determine whether cardiac extracellular matrix TN-C deposition after MI requires FN degradation. We found that treatment with angiotensin (ANG) II significantly down-regulated FN while remarkably up-regulated TN-C in co-cultured cardiomyocytes and fibroblasts. Inhibitors of matrix metalloproteinase (MMP)-2, MMP-3 or MMP-9 significantly attenuated ANG II-induced loss of FN and obviously blunted ANG II-induced re-expression of TN-C in co-cultured cells. Moreover, FN fragments dose-dependently induced the deposition of TN-C. In addition, MI induced a significant reduction of FN protein expression and a marked elevation of TN-C expression level at day 7 after MI compared with the sham group. The present findings suggest that cardiac TN-C matrix deposition after MI is induced by FN degradation, which is dependent on the activation of MMPs. These findings might contribute to gain mechanistic insights into the regulation of TN-C formation after MI.

Overexpression of angiotensin II type 2 receptor suppresses neointimal hyperplasia in a rat carotid arterial balloon injury model.

Angiotensin II (ANG II) type 2 receptor (AT2R) has been recognized to suppress the proliferation of vascular smooth muscle cells (VSMCs). The aim of the present study was to determine whether AT2R overexpression inhibits neointimal hyperplasia in a rat carotid arterial balloon injury model and to examine the underlying mechanisms of its activity. Balloon-injured rats receiving Ad-AT2R showed significant diminutions in neointimal area and intima/media ratio compared to non-treated rats or rats receiving adenovirus containing green fluorescent protein (Ad-GFP). In addition, extracellular regulated kinase 1/2 (ERK1/2) and basic transcription element-binding protein 2 (BTEB2) were significantly down-regulated in the arteries and VSMCs of Ad-AT2R-treated rats and compared to Ad-GFP-treated rats. However, Ad-AT2R transfection failed to affect the expression of ANG II type 1 receptor (AT1R) in carotid arteries and cultured VSMCs. The present study provides direct evidence that AT2R plays a beneficial role in balloon injury-induced neointimal hyperplasia, which is mainly attributed to the inhibition of VSMC proliferation and involves the down-regulation of the ERK1/2 and BTEB2 pathways, but is independent of the expression of AT1R.

BTEB2 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model.

Basic transcription element-binding protein 2 (BTEB2) is a regulator of the proliferation and phenotypic changes of vascular smooth muscle cells (SMCs). The aim of the present study was to determine whether or not BTEB2 knockdown inhibits balloon injury-induced neointimal hyperplasia attributed to the proliferation and phenotypic changes of vascular SMCs. We found that the knockdown of BTEB2 with antisense oligonucleotides (Ad-As-BTEB2) significantly reduced the intima/media ratio compared to uninjured arteries and vessels treated with Ad-LacZ. Knockdown of BTEB2 suppresses the proliferation of cultured vascular SMCs, concurrent with the down-regulation of proliferating cell nuclear antigen, angiotensin II type 1 receptor and platelet-derived growth factor BB. In addition, BTEB2 knockdown caused the up-regulation of the differentiation marker smooth muscle α-actin and down-regulation of the dedifferentiation marker embryonic smooth muscle myosin heavy chain. The present study provides direct evidence that BTEB2 plays a critical role in balloon injury-induced neointimal hyperplasia, which is closely linked to vascular SMC proliferation and phenotypic modulation. This study highlights the fact that BTEB2 may be a potential target for the prevention of restenosis after vascular intervention.

Increased expression of calpain and elevated activity of calcineurin in the myocardium of patients with congestive heart failure.

The angiotensin (Ang) II/Ang II receptor (ATR)-associated calcium signaling pathway is the major cause of ventricular remodelling in patients with congestive heart failure (CHF). However, the calcium-regulated proteinases responsible for Ang II-induced remodelling are not well understood. We investigated the profiles of the Ang II/ATR/calpain/calcineurin (CaN) pathway in human failing heart. We measured both the plasma and cardiac levels of Ang II and cardiac mRNA expression of ATR in 39 patients with CHF and 38 healthy controls. Importantly, protein expression of calpains, cleavage of cain/cabin1 and activity of CaN were tested. Both plasma and cardiac levels of Ang II were significantly increased in patients with CHF (both p<0.01), and the plasma Ang II concentration was closely correlated with the parameters of ventricular remodelling (r=+/-0.29-0.65, p<0.05 or <0.01). In addition, the cardiac level of AT1R but not AT2R was significantly upregulated in mild failing hearts (p<0.05) but dramatically downregulated in severe failing ones (p<0.01). CHF was associated with a marked upregulation of calpains, an increased cleavage of cain/cabin1, and the activation of CaN in the failing ventricular tissue. In patients with CHF, calpain upregulation was associated with an increase in cleavage of cain/cabin1 and the activation of CaN, indicating that these changes in calcium-regulated proteinases contribute to Ang II-induced cardiac remodelling.

[Cloning and sequence analysis of the molecular-adjuvant gene of the complement C3d of mouse].

OBJECTIVE: Considering that the complement C3d plays a stronger positive role in the control of immunologic system, we constructed the recombinant plasmid of the molecular-adjuvant gene of the complement C3d in order to enhance the immunologic efficacy of the gene vaccine. METHODS: The main points were amplifying the segment of complement C3d gene by using of PCR; inserting it into PGEM-T; detecting it by digesting with Eco RI and sequencing; the whole length being 897 bp; then sub-cloning it into pVAX1. RESULTS: The DNA sequencing confirmed the C3d sequence. CONCLUSION: We have successfully cloned the gene of C3d and constructed the recombinant plasmid of pVAX1 C3d.