RESUMEN
RATIONALE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease of desmosome proteins characterized by fibroadipogenesis in the myocardium. We have implicated signaling properties of junction protein plakoglobin (PG) in the pathogenesis of ARVC. OBJECTIVE: To delineate the pathogenic role of PG in adipogenesis in ARVC. METHODS AND RESULTS: We generated mice overexpressing PG, either a wildtype (PG(WT)) or a truncated (PG(TR)), known to cause ARVC, in the heart; and PG null (PGâ»/â») embryos. PG(WT) and PG(TR) mice exhibited fibro-adiposis, cardiac dysfunction, and premature death. Subcellular protein fractionation and immunofluorescence showed nuclear localization of PG(WT) and PG(TR) and reduced membrane localization of PG(TR). Coimmunoprecipitation showed reduced binding of PG(TR) but not PG(WT) to desmosome proteins DSP and DSG2. Transgene PG(WT) and PG(TR) were expressed in c-Kit+:Sca1+ cardiac progenitor cells (CPCs) isolated from the hearts of PG(WT) and PG(TR) by fluorescence activated cell sorting. CPCs isolated from the transgenic hearts showed enhanced adipogenesis, increased levels of adipogenic factors KLF15, C/EBP-α and noncanonical Wnt5b, and reduced level of CTGF, an inhibitor of adipogenesis. Treatment with BIO activated the canonical Wnt signaling, reversed the proadipogenic transcriptional switch and prevented adipogenesis in a dose-dependent manner. Moreover, c-Kit+ CPCs, isolated from PGâ»/â» embryos, were resistant to adipogenesis, expressed high mRNA levels of CTGF and other canonical Wnt signaling targets. CONCLUSIONS: Nuclear PG provokes adipogenesis in c-Kit+ CPCs by repressing the canonical Wnt signaling and inducing a proadipogenic gene expression. The findings suggest that adipocytes in ARVC, at least in part, originate from c-Kit+ CPCs.
Asunto(s)
Adipocitos/citología , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Diferenciación Celular/fisiología , Núcleo Celular/metabolismo , Miocitos Cardíacos/citología , Células Madre/citología , gamma Catenina/metabolismo , Adipogénesis/fisiología , Animales , Displasia Ventricular Derecha Arritmogénica/patología , Células Cultivadas , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Transducción de Señal/fisiología , Proteínas Wnt/metabolismo , gamma Catenina/deficiencia , gamma Catenina/genéticaRESUMEN
BACKGROUND: Slippage and pouch dilation are the most common surgical complications after laparoscopic adjustable gastric banding, yet few reports have described the specific outcomes after band repositioning for these complications. The objective of this study was to examine the intermediate outcomes of our patients who underwent band repositioning for slippage or pouch dilation. METHODS: From October 2000 to December 2005, 1275 patients underwent laparoscopic adjustable gastric banding at our center. Of these, we retrospectively reviewed the data of the first 40 consecutive patients (92.5% women, mean age 41.7 years, mean preoperative weight 123.3 kg [range 86.2-180.5], mean body mass index 44.8 kg/m2 [range 34.6-66.4]) who presented with anterior slippage (52.5%), posterior slippage (20%), or pouch dilation (27.5%, 7 with associated hiatal hernias) that required band repositioning (95%) or explantation (5%). RESULTS: The average time between laparoscopic adjustable gastric banding and reoperation was 22.9 months. Before band repositioning, the mean weight was 91.5 kg, mean body mass index was 33.2 kg/m(2), and mean percentage of excess weight loss was 49.4% (range 1-79.8%). One patient had a recurrent anterior slippage that required a second band repositioning. Two bands were explanted, one for intraoperative gastric perforation and one at the patient's request. The mean percentage of excess weight loss after band repositioning was 48.1% (range 18.2-77.4%) at an average follow-up of 17.6 months (range 6-36). To date, 38 (95%) of the 40 patients have functioning bands. Co-morbidity resolution was seen in 3 (60%) of 5 patients with diabetes, 13 (65%) of 20 with hypertension, and 8 (72%) of 11 with sleep apnea. CONCLUSION: Laparoscopic band repositioning can result in preservation of most of the initial weight loss and co-morbidity resolution.
Asunto(s)
Gastroplastia/métodos , Gastroscopía , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/cirugía , Adulto , Índice de Masa Corporal , Dilatación Patológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to examine 1,014 consecutive laparoscopic adjustable gastric banding (LAGB) procedures with up to 48 months of followup, including evolution and changes in surgical technique, learning curve issues, weight loss outcomes, and complications. STUDY DESIGN: Between October 2000 and December 2004, 1,014 consecutive patients (81.8% women, mean age 42.3 years, mean body mass index 47.7 +/- 8.6 kg/m(2)) underwent LAGB operation at our center. Perigastric dissection was used in the first 44 patients; pars flaccida technique was used for the latter 970 patients. Fluoroscopy-guided adjustments were performed and patients received intensive followup. RESULTS: Excess weight loss at 12, 24, 36, and 48 months was 40.5 +/- 17%, 52.9 +/- 19.5%, 62 +/- 20.9%, and 64.3 +/- 19%, respectively, with data available in > 85% of patients who had reached each of the time intervals. Patients with lower preoperative body mass index had higher excess weight loss initially, but this difference was not apparent at 3 and 4 years' followup. At 36 and 48 months, respectively, 73.5% and 75% of patients had > 50% excess weight loss. Perigastric dissection led to 9 of 44 (20.5%) slippages, compared with 14 of 970 (1.4%) with pars flaccida technique. Other complications included 2 erosions (0.2%), 5 tubing breaks (0.5%), 7 access port problems (0.7%), and 14 acute stoma obstructions (1.4%). Eight (0.8%) bands were explanted. No deaths occurred. CONCLUSIONS: LAGB can achieve effective and safe weight loss. Change from perigastric to pars flaccida technique reduced slippage rate. Preoperative body mass index alone was not found to be a predictor of effective weight loss in the longterm.
Asunto(s)
Gastroplastia/métodos , Laparoscopía , Obesidad Mórbida/cirugía , Adolescente , Adulto , Anciano , Análisis de Varianza , Índice de Masa Corporal , Distribución de Chi-Cuadrado , Femenino , Fluoroscopía , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Severe obesity is associated with type 2 diabetes and hypertension. Improvement in these comorbidities after surgically-induced weight loss has been documented, and laparoscopic adjustable gastric banding (LAGB) is an effective weight loss operation. METHODS: Of 840 patients who underwent Lap-Band, data are available in 402 out of 413 patients whose surgery took place at >/= 1 year ago. Preoperative and follow-up data were studied retrospectively to examine the effect of Lap-Band-induced weight loss on diabetes and hypertension. RESULTS: Of 413 patients with at least 1 year postoperative follow-up, 53 (12.8%) were taking medications for type 2 diabetes preoperatively and 189 (45.7%) were on antihypertensive medications. 66% (n=35) of diabetic patients were also hypertensive. Resolution of diabetes was observed in 66% at 1-year and 80% at 2-year follow-up. HbA1c dropped from 7.25% (5.6-11.0, n=53) preoperatively to 5.58% (5.0-6.2, n=15) at 2 years after surgery. Hypertension resolved in 59.8% and 74% at 1 and 2 years, respectively. Percent excess weight loss (%EWL) was lower for diabetic patients than for our cohort population (39.2% vs 41.2% at 1 year, 46.7% vs 54.2% at 18 months, and 52.6% vs 63.3% at 2 years, respectively). Patients in whom diabetes was improved but not resolved had lower %EWL than did those whose diabetes went into remission (27.0% at 1 year and 26.5% at 2 years). Patients with the shortest duration of diabetes (<5 years) and better weight loss after surgery achieved higher resolution rates. CONCLUSIONS: Dramatic improvement in - and frequent resolution of - diabetes and hypertension have been observed as a result of weight loss after Lap-Band surgery.