Down-Regulation of miR-34a-5p Potentiates Protective Effect of Adipose-Derived Mesenchymal Stem Cells Against Ischemic Myocardial Infarction by Stimulating the Expression of C1q/Tumor Necrosis Factor-Related Protein-9.

Adipose-derived stem cells (ADSCs) have shown great promise for the treatment of myocardial infarction (MI), although their potential therapeutic mechanism remains poorly understood. Growing evidence has implicated microRNAs (miRNAs or miRs) in the biological processes whereby ADSCs could ameliorate cardiovascular disease. In this study, we explored the contribution of miR-34a-5p down-regulation to the protective actions of ADSCs against MI. We initially identified the interaction between miR-34a-5p and C1q/tumor necrosis factor-related protein-9 (CTRP9) through in silico analysis. We next tested the effects of miR-34a-5p and CTRP9 on the expression of extracellular signal-regulated kinase 1 (ERK1), matrix metalloproteinase-9 (MMP-9), nuclear factor (erythroid-derived 2)-like 2 (NRF2), and antioxidant proteins [manganese superoxide dismutase (MnSOD), and heme oxygenase-1 (HO-1)] through gain- and loss-of-function tests. In other experiments, we assessed the proliferation, migration, and apoptosis of ADSCs using the EdU assay, scratch test, Transwell assay, and flow cytometry. Finally, we studied whether miR-34a-5p/CTRP9 axis could modulate the protective effect of ADSCs against MI during stem cell transplantation in MI mouse models. miR-34a-5p could target and down-regulate CTRP9 in cardiomyocytes. Down-regulated miR-34a-5p increased the expression of ERK1, MMP-9, NRF2, MnSOD, and HO-1, whereas down-regulation of miR-34a-5p or up-regulation of CTRP9 in vitro promoted ADSC proliferation and migration and inhibited ADSC apoptosis. Moreover, miR-34a-5p down-regulation or CTRP9 up-regulation promoted the protective role of ADSCs against MI damage in vivo. Thus, inhibition of miR-34a-5p may facilitate ADSC's protective function against MI damage by stimulating the expression of CTRP9.

Downregulation of Sirt1 as aging change in advanced heart failure.

BACKGROUND: In congestive heart failure the balance between cell death and cell survival in cardiomyocytes is compromised. Sirtuin 1 (Sirt1) activates cell survival machinery and has been shown to be protective against ischemia/reperfusion injury in murine heart. The role of Sirt1 in heart failure, especially in human hearts is not clear. RESULTS: The expression of Sirt1 and other (associated) downstream molecules in human cardiomyocytes from patients with advanced heart failure was examined. Sirt1 was down-regulated (54.92% ± 7.80% in advanced heart failure samples compared with healthy control cardiomyocytes). The modulation of molecules involved in cardiomyocyte survival and death in advanced heart failure were also examined. The expression of Mn-superoxide dismutase and thioredoxin1, as well as an antiapoptotic molecule, Bcl-xL, were all significantly reduced in advanced heart failure cardiomyoctes (0.71 ± 0.02-fold, 0.61 ± 0.05-fold, and 0.53 ± 0.08-fold vs. control, respectively); whereas the expression of proapoptotic molecule Bax was significantly increased (1.62 ± 0.18-fold vs. control). Increased TUNEL-positive number of cardiomyocytes and oxidative stress, confirmed by 8-hydorxydeoxyguanosine staining, were associated with advanced heart failure. The AMPK-Nampt-Sirt1 axis also showed inhibition in advanced heart failure in addition to severely impaired AMPK activation. Increased p53 (acetyl form) and decreased FoxO1 translocation in the nucleus may be the mechanism of down-regulation of antioxidants and up-regulation of proapoptotic molecules due to low expression of Sirt1. CONCLUSION: In advanced heart failure, low Sirt1 expression, like aging change may be a significant contributing factor in the downregulation of antioxidants and upregulation of proapoptotic molecules through the p53, FoxO1, and oxidative stress pathways.

P-side up AlGaInP-based light emitting diodes with dot-patterned GaAs contact layers.

High-brightness p-side up AlGaInP-based red light emitting diodes (LEDs) with dot-patterned GaAs contact layer and surface rough structure are presented in this article. Initial LED structure of p-GaP/AlGaInP/GaAs is epitaxially grown using metal organic chemical vapor deposition technique. Using novel twice transferring process, the p-GaP layer is remained at the top side as both the current spreading and-window layer. Dot patterned GaAs contact dots are formed between main structure and rear mirror to improve light reflection and current spreading. Moreover, the surface of p-GaP window is further textured by nano-sphere lithography technique for improving the light extraction. Significant improvement in output power is found for AlGaInP LEDs with GaAs contact dots and roughened p-GaP window as compared with those of LEDs with traditional n-side up and p-side up structures without roughened surfaces.

Early endovascular experience for treatments of Takayasu's arteritis.

BACKGROUND: Takayasu's arteritis (TA) is a chronic inflammatory disease that involves the aorta and its major branches; however, only limited data are available on TA in Taiwan. This study presents the clinical features, angiographic findings, and response to treatment of patients with TA at a single institute in Taiwan. METHODS: A search of the hospital database for ICD9 code 446.7 (Takayasu's disease) between 1990 and 2010 was performed. Seven cases fulfilled the 1990 American College of Rheumatology diagnostic criteria for Takayasu's disease. Angiographic classification was made according to the guidelines of the 1994 International TA Conference in Tokyo. RESULTS: All of our cases were female, and the median age at diagnosis was 27.5 years (range 14-36 years). Four patients had an angiographic classification of type I (57.1%), two were classified as type V (28.6%), and one was classified as type III (14.3%). The most common symptoms/signs were dizziness and vascular bruits. Two patients underwent bypass surgery, four endovascular stenting, and one hybrid bypass with stenting. After a mean follow-up period of 50.3 ± 68.2 months (range 12.3-199.6 months), both the procedure success and survival rates were 100%. There were four restenosis cases (57.1%), one in the surgical bypass group without symptoms (33.3%), and three in the endovascular group (60%), five restenosis in 14 stents (35.7%). Also, these three patients received secondary endovascular procedure for percutaneous transluminal angioplasty or restenting. CONCLUSION: There have not been any case series reports about treatments of Takayasu's disease in Taiwan to date, based on a search of the PubMed/MEDLINE and Cochrane Library databases. Although endovascular treatment is becoming more prevalent, the restenosis rate is still high, and long-term follow-up and further strategy for restenosis management are the main challenges.

Factors predictive of distal stent graft-induced new entry after hybrid arch elephant trunk repair with stainless steel-based device in aortic dissection.

OBJECTIVES: Stent graft-induced new entry (SINE) has been increasingly observed after thoracic endovascular aortic repair of aortic dissection. We illustrate the possible mechanism by exploring predictive factors of late distal SINE after hybrid arch elephant trunk repair for aortic dissection. METHODS: From November 2006, to May 2011, 20 of 99 patients underwent hybrid arch repair using the elephant trunk graft as the proximal landing zone. After a mean follow-up period of 27.9 ± 12.0 months, 12 patients had late distal SINE events and the others were free of events. False lumen remodeling level was observed and maximal longitudinal diameter, average of longitudinal and transverse maximal diameter, circumference, and area of true lumen were analyzed for precise size selection of stent graft before and after the procedure. Taper ratio, true lumen:aorta ratio, prestent grafting oversizing ratio, poststent grafting oversizing ratio, and expansion mismatch ratio of distal true lumen were proposed and calculated for further evaluation of the mechanism of late distal SINE. RESULTS: Only the area oversizing ratio between true lumen and the distal selected stent graft at the presumed distal end of stent grafting was found as a significant predictive factor of SINE before procedure (4.00 ± 2.96 vs 1.98 ± 0.66 for SINE vs non-SINE, respectively; P = .031). The significant difference of the expansion mismatch ratio of true lumen between the 2 groups was found not only in the size measurement of mean diameter (1.48 ± 0.29 vs 1.22 ± 0.15; P = .039), but also in the area (2.39 ± 0.85 vs 1.58 ± 0.42; P = .031) and circumference (1.43 ± 0.27 vs 1.18 ± 0.14; P = .016) after stent grafting. CONCLUSIONS: We found that taper ratio is not an optimal criteria for stent graft size selection and distal oversizing calculated by true-lumen area is a significant factor causing delayed distal SINE. Use of the prestenting area oversizing ratio should be limited.

Reintervention for distal stent graft-induced new entry after endovascular repair with a stainless steel-based device in aortic dissection.

OBJECTIVE: Stent graft-induced new entry (SINE) has been increasingly observed after thoracic endovascular aortic repair (TEVAR) for aortic dissection. We investigated the mechanism of late distal SINE, prevention strategies, proper size selection of the stent graft, and implantation sequence. METHODS: From November 2006 to May 2011, 99 patients with aortic dissection underwent TEVAR with Zenith TX2 stent grafts (Cook, Bloomington, Ind) at our center. Among them, 27 distal SINEs were recognized. Eight of these patients with complicated distal SINE required intervention with new distal endografts, and all were enrolled for further analysis. RESULTS: Eight of the 27 patients with distal SINE underwent a secondary endograft procedure from February 2011 to July 2011. All were successfully treated without any complications or deaths. A high taper ratio (35%±11%) and excessive oversizing of the true lumen area at the distal stent level (293%±76%) were noted among these patients. CONCLUSIONS: The incidence of distal SINE seemed to be high; however, there were also low rates of death and complications after TEVAR for aortic dissection using stainless steel-based stent grafts. Complicated distal SINE can successfully be resolved by distal endograft implantation. Excessive oversizing of the distal stent graft, as measured by the true lumen area, may be a significant factor causing delayed distal SINE. Precise size selection is crucial for the distal end of the stent, especially for high taper ratio dissection pathology in which the implantation sequence of a distal small-sized stent graft first might be considered to prevent future distal SINE.

Repair of Traumatic Tricuspid Regurgitation.

UNLABELLED: Severe tricuspid regurgitation (TR) after blunt chest trauma is rare and often results from damage to the subvalvular apparatus. When injured, the damaged subvalvular apparatus may break immediately or at a later stage due to mechanical fatigue. We report the case of a 30-year-old man who sustained a blunt thoraco-abdominal trauma in a motorbike accident. The patient's condition immediately after the accident precluded any intervention for the moderate TR that was detected by transesophageal echocardiography. However, he later developed a severe TR which required surgical intervention 11 months after the accident. The operative findings included a ruptured anterior common chordae, a contracted and perforated anterior leaflet, and an enlarged annulus. A satisfactory valve competence was achieved with several techniques including chordae re-implantation, suture commissurotomy, and ring annuloplasty. This report highlights the unpredictable course of deterioration in traumatic TR and the possibility of complex repair. KEY WORDS: Blunt cardiac injury; Tricuspid regurgitation; Tricuspid valve repair.

Aortic remodeling after endovascular repair with stainless steel-based stent graft in acute and chronic type B aortic dissection.

OBJECTIVE: This study analyzes the experience of a single center using hybrid stainless steel-based endovascular stent graft repair of acute complicated and chronic type B aortic dissection aneurysm, and assesses the proximal and distal aortic morphologic changes of the midterm results. METHODS: Between November 2006 and March 2011, 61 patients with type B aortic dissection underwent stainless steel-based stent graft repair and were divided into an acute complicated dissection group (AD; n = 33) and a chronic dissection aneurysm group (CD; n = 28). Serial computed tomography (CT) images were obtained to evaluate the changes of true and false lumen diameter at four levels during the postoperative period. RESULTS: The stent graft was successfully implanted in all patients (100%), with two surgical mortalities in the AD group and low perioperative morbidity (3.6%) of stroke and paraplegia. The cumulative survival rates of the two groups were similar (77.6% and 89.0%; P = .585) in a mean follow-up period of 24.1 ± 15.6 months. Complete thrombosis of the thoracic false lumen down to the diaphragm level was achieved in 80.6% of the patients in the AD group and 88.5% in the CD group without significant difference (P = .221), but the complete regression rate of the thoracic false lumen down to the diaphragm level showed a tendency of propitious remodeling in the AD group (54.8% vs 30.8%; P = .068). During follow-up, despite the proximal changes of stented true and adjacent false lumen diameter being significantly increased and decreased, respectively, in both acute and chronic settings (P < .05), they were less prominent at the distal aorta in the CD aneurysm group. Intimomedial erosion of the distal end of the stent graft occurred in both acute (n = 6; 18.9%) and chronic (n = 10; 35.7%; P = .121) dissection settings after mean follow-up of 14.0 ± 4.8 months in the AD group and 24.8 ± 5.9 months in the CD group. Three patients with chronic dissection developed either pseudoaneurysm or true lumen compromise by expanded false lumen thrombi and required re-endografting. CONCLUSIONS: Endovascular stainless steel-based stent graft implantation with vascular bypass to gain a sufficient proximal landing zone is feasible for type B aortic dissection and has low early and midterm mortality and morbidity in both the acute and chronic phases. Although early intervention might result in more favorable aortic remodeling with a higher possibility of complete regression and lower risk of late distal erosion, longer-term follow-up still necessitates continuous careful surveillance of the entire aorta, especially the distal condition.

Association of polymorphisms in genes involved in the dopaminergic pathway with blood pressure and uric acid levels in Chinese females.

Since the high degree of heritability of physiological traits was demonstrated by twin and adoption studies, contemporary researchers in the fields of clinical medicine, behavioral science, and genetics have acknowledged the crucial role of genetic factors in human physiology. The study described herein explores the association between physiological parameters and the dopaminergic system using molecular genetic techniques. A total of 558 Taiwanese female volunteers, ranging from 16 to 17 years, were recruited. Single nucleotide polymorphisms in genes involved in the dopaminergic pathway were selected for analysis. Systolic blood pressure and diastolic blood pressure were associated significantly with the catechol-O-methyltransferase (COMT) Val158Met polymorphism and the dopamine ß-hydroxylase (DBH) C1021T polymorphism. Furthermore, plasma uric acid was associated significantly with the COMT Val158Met polymorphism. Our study suggests the possible involvement of genetic polymorphisms in COMT and DBH in the regulation of blood pressure and plasma uric acid.

High-output heart failure resulting from an obscure traumatic arteriovenous fistula.

Traumatic arteriovenous fistula (AVF) is not an uncommon disorder, but late discovery and the presentation of high-output heart failure is very rare. This patient did not know that he had traumatic AVF after a gunshot injury in the left thigh 14 years ago. The major presentation of the AVF was signs of heart failure. We performed surgical repair after making the diagnosis. The patient recovered with an uneventful course. This report stresses the importance of history-taking and physical examination in making the diagnosis of traumatic AVF.