Search

Purpose This RCT study investigates the effects of a self-management program on clinical status indexes of COPD patients. Design In this study, 50 COPD patients referred to the respiratory clinic participated. Methods Patients were randomly assigned to control and intervention groups. The control group received standard care, and the intervention group received standard care plus the self-management program. Patients were assessed by spirometry, Modified Borg scale, and 6-minute walking test at the baseline and the end of 12-weeks. Paired t-test, independent t-test, and chi-square were used to analyze variables. Findings No significant difference was noted in the spirometry indexes mean in the two groups; however, significant differences were noted in dyspnea and exercise tolerance at the end. Conclusion/clinical relevance Using the 5A model can lead to increased exercise tolerance and decreased dyspnea in COPD patients. Therefore, this self-management program is recommended as an effective way to improve their functional status.

Background: Four-and-a-half LIM domain protein 2 (FHL2) is an adaptor molecule that regulates signalling cascades and gene transcription. We have uncovered vasculoprotective and atheroprotective effects of FHL2 knockout in mice. Since B cells could regulate these processes, we investigated the potential role of FHL2 in B cell function and activity. Methods and Results: Under basal conditions, FHL2-/- mice presented a mild splenomegaly (84.0±9.0 vs 68.0±5.0mg), associated with bigger spleen follicles (1.6 fold) and higher proportions of spleen B cells (56.0±2.0 vs 40.0±9.0%) vs WT mice. Flow cytometry confirmed significantly higher (p Conclusion: These results suggest that FHL2 plays a critical role in spleen antibody production in response to a T-dependent antigen, possibly by affecting activation or antigen presentation by Fo T helper cells.

Objective: Recent data point to an important immunomodulatory role for neural guidance molecules, including semaphorin 3a (Sema-3A), in inflammatory diseases. Sema-3A is a secreted member of the Sema family and is produced by several immune cells including macrophages. We found that Sema-3A receptors are expressed in macrophages and in atherosclerotic plaques. Approach and results: To investigate the role of Sema-3A in atherosclerosis, ApoE-/- mice were administered with a Sema-3A overexpressing or a control plasmid and were fed a high fat diet for 9 weeks. Sema-3A receptors were expressed in macrophages and atherosclerotic plaques. Our results show that Sema-3A overexpressing mice had significantly smaller atherosclerotic plaques than control mice in the aortic sinus (0.3±0.02 vs. 0.4±0.03 mm 2 ), the brachiocephalic artery (0.04±0.01 vs. 0.1±0.01 mm 2 ) and the aorta (9.5±1.4 vs 15.3±2.9%), assessed by oil red O staining. No differences were observed in plaque stability, measured by collagen and smooth muscle cell alpha-actin staining. However, there was significantly less (2-fold) macrophage content in the plaques of Sema-3A compared to control mice, associated with decreased circulating monocytes determined by flow cytometry as cd11b positive and Gr-1 negative cells (4.97±0.74 vs. 7.2±0.62%). To better define the involved mechanisms, we investigated macrophage function In vitro and found that recombinant Sema-3A increased by 4 fold migration of M2 but not M1 macrophages. In addition, active beta-1 integrin expression was significantly enhanced (2-fold) by Sema-3A in human M2 macrophages. Importantly, Sema-3A induced a significant increase (by 50%) of focal adhesion kinase phosphorylation. Conclusions: Our data show that Sema-3A prevents atherosclerotic plaque formation in ApoE -/- mice. This may be due in part to enhanced motility and function of M2 macrophages through regulation of beta-1 integrin.

Background: Four-and-a-half LIM domain protein-2 (FHL2) is expressed in endothelial and vascular smooth muscle cells. It negatively regulates endothelial cell survival and migration, but its role in atherogenesis is unknown. Methods and Results: FHL2-deficient (FHL2-/-) mice were crossed with apolipoprotein E-deficient (ApoE-/-) mice to generate ApoE/FHL2-/- mice. After high-fat, high-cholesterol diet, ApoE/FHL2-/- mice displayed significantly smaller atherosclerotic plaques than ApoE-/- mice in the aortic sinus, the brachiocephalic artery and the aorta. This was associated with significantly enhanced collagen and smooth muscle cell contents and a significant 2-fold reduction of macrophage content within the plaques of ApoE/FHL-2-/- vs ApoE-/- mice. There was a significant reduction in aortic ICAM-1 mRNA and VCAM-1 protein expression in the plaques of ApoE/FHL2-/- mice. Aortic gene expression of CX3CL1 and CCL5 was significantly increased in ApoE/FHL2-/- vs ApoE-/- mice. Peritoneal thioglycollate injection elicited equivalent numbers of monocytes and macrophages in both groups, but a significantly lower number of pro-inflammatory Ly6C-high monocytes were recruited in ApoE/FHL2-/- vs ApoE-/- mice. Furthermore, mRNA levels of CX3CR1 were 2-fold higher in monocytes from ApoE/FHL2-/- vs ApoE-/- mice. Finally, we investigated the potential importance of myeloid cell FHL2 deficiency in atherosclerosis. After being irradiated, ApoE-/- or ApoE/FHL2-/- mice were transplanted with ApoE-/- or ApoE/FHL2-/- bone marrow. After high-fat, high-cholesterol diet, both chimeric groups developed significantly smaller plaques than ApoE-/- mice transplanted with ApoE-/- bone marrow. Conclusion: These results suggest that FHL2 in both myeloid and vascular cells may play an important role in atherogenesis by promoting pro-inflammatory chemokine production, adhesion molecule expression, and pro-inflammatory monocyte recruitment.

Four-and-a-half LIM domain protein-2 (FHL2) is expressed in endothelial and vascular smooth muscle cells. It negatively regulates endothelial cell survival and migration, but its role in atherogenesis is unknown. To investigate the role of FHL2 in atherosclerosis, FHL2-deficient (FHL2-/-) mice were crossed with ApoE-deficient (ApoE -/-) mice, to generate ApoE/FHL2-/- mice. After 7 weeks of high fat diet, ApoE/FHL2-/- mice had significantly smaller (P

Semaphorin3A (SEMA3A) is a secreted member of the Semaphorin family, first found to play a role in axon guidance. Recently many studies revealed immune functions for this protein. However, how SEMA3A may regulate monocyte and macrophage functions associated with atherosclerosis is unknown. An early step in plaque formation is the adhesion of monocytes on activated endothelial cells expressing adhesion molecules. However, we found that 25-100 ng/ml SEMA 3A did not affect the adhesion of monocyes on ICAM-1- or VCAM-1-coated plates. Similarly, stimulation of mouse carotid arteries with SEMA3A in an ex-vivo perfusion system, either administered alone or in conjunction with TNF-α, did not increase adhesiveness of monocytes injected in the intraluminal compartment. Furthermore SEMA3A did not stimulate monocyte migration in a boyden chamber assay. However SEMA3A had significant effects on macrophages, the most abundant cells in the plaque. Inefficient apoptotic cell phagocytosis and macrophage retention in the artery wall are hallmarks of atherosclerosis progression. We found that SEMA3A increased the migration of M2 “wound healing” macrophages more than 4-fold (p

OBJECTIVE Four-and-a-half LIM domain protein-2 (FHL2), a member of the FHL family of proteins, is expressed in endothelial and vascular smooth muscle cells. FHL2 negatively regulates endothelial cell survival and migration, but its role in atherogenesis is unknown. METHODS AND RESULTS To investigate the role of FHL2 in atherosclerosis, we crossed FHL2 knockout (FHL2-/-) with apolipoprotein (Apo) E-deficient (ApoE -/-) mice, and fed them a high fat diet for 7 weeks. Despite a total plasma cholesterol levels comparable to the ApoE-/- mice, FHL2-/-ApoE-/- mice showed a strong increase in plasma HDL-cholesterol as compared to ApoE -/- mice (P2 ) and aorta (6.9±0.9 vs 10.3±1%) (P CONCLUSIONS These results suggest that FHL2 may play an important role in atherosclerosis by promoting plaque formation, through upregulation of adhesion molecule expression and suppression of regulatory T cells.