RESUMO
Obesity imposes well-established deficits to endothelial function. We recently showed that obesity-induced endothelial dysfunction was mediated by disruption of the glycocalyx and a loss of Kir channel flow sensitivity. However, obesity-induced endothelial dysfunction is not observed in all vascular beds: visceral adipose arteries (VAAs), but not subcutaneous adipose arteries (SAAs), exhibit endothelial dysfunction. To determine whether differences in SAA versus VAA endothelial function observed in obesity are attributed to differential impairment of Kir channels and alterations to the glycocalyx, mice were fed a normal rodent diet, or a high-fat Western diet to induce obesity. Flow-induced vasodilation (FIV) was measured ex vivo. Functional downregulation of endothelial Kir2.1 was accomplished by transducing adipose arteries from mice and obese humans with adenovirus containing a dominant-negative Kir2.1 construct. Kir function was tested in freshly isolated endothelial cells seeded in a flow chamber for electrophysiological recordings under fluid shear. Atomic force microscopy was used to assess biophysical properties of the glycocalyx. Endothelial dysfunction was observed in VAAs of obese mice and humans. Downregulating Kir2.1 blunted FIV in SAAs, but had no effect on VAAs, from obese mice and humans. Obesity abolished Kir shear sensitivity in VAA endothelial cells and significantly altered the VAA glycocalyx. In contrast, Kir shear sensitivity was observed in SAA endothelial cells from obese mice and effects on SAA glycocalyx were less pronounced. We reveal distinct differences in Kir function and alterations to the glycocalyx that we propose contribute to the dichotomy in SAA versus VAA endothelial function with obesity.NEW & NOTEWORTHY We identified a role for endothelial Kir2.1 in the differences observed in VAA versus SAA endothelial function with obesity. The endothelial glycocalyx, a regulator of Kir activation by shear, is unequally perturbed in VAAs as compared with SAAs, which we propose results in a near complete loss of VAA endothelial Kir shear sensitivity and endothelial dysfunction. We propose that these differences underly the preserved endothelial function of SAA in obese mice and humans.
Assuntos
Artérias/metabolismo , Gordura Intra-Abdominal/irrigação sanguínea , Obesidade/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Gordura Subcutânea/irrigação sanguínea , Adulto , Animais , Células Cultivadas , Endotélio Vascular/metabolismo , Glicocálix/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Canais de Potássio Corretores do Fluxo de Internalização/genéticaRESUMO
BACKGROUND: Neck fat distribution plays an important role in aging, yet how fat distribution changes with age is largely unknown. This study used volumetric computed tomography in live patients to characterize neck fat volume and distribution in young and elderly women. METHODS: A retrospective analysis was conducted of head and neck computed tomographic angiographs of 20 young (aged 20 to 35 years) and 20 old (aged 65 to 89 years) women. Fat volume in the supraplatysmal and subplatysmal planes was quantified. Distribution of fat volume was assessed by dividing each supraplatysmal and subplatysmal compartment into upper, middle, and lower thirds. RESULTS: Total supraplatysmal fat volume was greater than subplatysmal in all patients. Young patients had more total supraplatysmal fat than old patients (p < 0.0001). No difference was found between age groups in subplatysmal fat (p > 0.05). No difference was found between upper/middle/lower third supraplatysmal fat volumes in young patients. When comparing supraplatysmal thirds within the elderly population, the middle third fat volume (28.58 ± 20.01 cm3) was greater than both upper (18.93 ± 10.35 cm3) and lower thirds (15.46 ± 11.57 cm3) (p < 0.01). CONCLUSIONS: This study suggests that total supraplatysmal fat volume decreases with age. Older patients had more fat volume in the upper and middle thirds compared with the lower third of the supraplatysmal fat compartment, whereas young patients had more evenly distributed fat. These results suggest that fat deposition and redistribution in the neck occur with age and may be a contributing factor to the obtuse cervicomandibular angle of the elderly.
Assuntos
Adiposidade/fisiologia , Envelhecimento/fisiologia , Gordura Subcutânea/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Angiografia por Tomografia Computadorizada/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Feminino , Humanos , Pescoço , Estudos Retrospectivos , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/fisiologia , Adulto JovemAssuntos
Síndrome de Cushing/induzido quimicamente , Dexametasona/efeitos adversos , Face/diagnóstico por imagem , Linfoma de Células T/tratamento farmacológico , Mandíbula/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Gordura Subcutânea/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Dexametasona/administração & dosagem , Face/irrigação sanguínea , Face/patologia , Humanos , Masculino , Especificidade de Órgãos , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/patologiaRESUMO
Background Pathophysiological mechanisms that connect obesity to cardiovascular disease are incompletely understood. FSP27 (Fat-specific protein 27) is a lipid droplet-associated protein that regulates lipolysis and insulin sensitivity in adipocytes. We unexpectedly discovered extensive FSP27 expression in human endothelial cells that is downregulated in association with visceral obesity. We sought to examine the functional role of FSP27 in the control of vascular phenotype. Methods and Results We biopsied paired subcutaneous and visceral fat depots from 61 obese individuals (body mass index 44±8 kg/m2, age 48±4 years) during planned bariatric surgery. We characterized depot-specific FSP27 expression in relation to adipose tissue microvascular insulin resistance, endothelial function and angiogenesis, and examined differential effects of FSP27 modification on vascular function. We observed markedly reduced vasodilator and angiogenic capacity of microvessels isolated from the visceral compared with subcutaneous adipose depots. Recombinant FSP27 and/or adenoviral FSP27 overexpression in human tissue increased endothelial nitric oxide synthase phosphorylation and nitric oxide production, and rescued vasomotor and angiogenic dysfunction (P<0.05), while siRNA-mediated FSP27 knockdown had opposite effects. Mechanistically, we observed that FSP27 interacts with vascular endothelial growth factor-A and exerts robust regulatory control over its expression. Lastly, in a subset of subjects followed longitudinally for 12±3 months after their bariatric surgery, 30% weight loss improved metabolic parameters and increased angiogenic capacity that correlated positively with increased FSP27 expression (r=0.79, P<0.05). Conclusions Our data strongly support a key role and functional significance of FSP27 as a critical endogenous modulator of human microvascular function that has not been previously described. FSP27 may serve as a previously unrecognized regulator of arteriolar vasomotor capacity and angiogenesis which are pivotal in the pathogenesis of cardiometabolic diseases linked to obesity.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Doenças Cardiovasculares/metabolismo , Células Endoteliais/metabolismo , Gordura Intra-Abdominal/irrigação sanguínea , Microvasos/metabolismo , Neovascularização Fisiológica , Obesidade/metabolismo , Gordura Subcutânea/irrigação sanguínea , Vasodilatação , Adiposidade , Adulto , Proteínas Reguladoras de Apoptose/genética , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Células Cultivadas , Feminino , Humanos , Masculino , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/complicações , Obesidade/fisiopatologia , Fosforilação , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
AIMS: Low-grade chronic inflammation characterizes obesity and metabolic syndrome. Here, we aim at investigating the impact of the acute-phase protein long pentraxin 3 (PTX3) on the immune-inflammatory response occurring during diet-induced obesity. METHODS AND RESULTS: PTX3 deficiency in mice fed a high-fat diet for 20 weeks protects from weight gain and adipose tissue deposition in visceral and subcutaneous depots. This effect is not related to changes in glucose homeostasis and lipid metabolism but is associated with an improved immune cell phenotype in the adipose tissue of Ptx3 deficient animals, which is characterized by M2-macrophages polarization and increased angiogenesis. These findings are recapitulated in humans where carriers of a PTX3 haplotype (PTX3 h2/h2 haplotype), resulting in lower PTX3 plasma levels, presented with a reduced prevalence of obesity and decreased abdominal adiposity compared with non-carriers. CONCLUSION: Our results support a critical role for PTX3 in the onset of obesity by promoting inflammation and limiting adipose tissue vascularization and delineate PTX3 targeting as a valuable strategy for the treatment of adipose tissue-associated inflammatory response.
Assuntos
Proteína C-Reativa/deficiência , Dieta Hiperlipídica , Metabolismo Energético , Imunidade Inata , Mediadores da Inflamação/metabolismo , Inflamação/prevenção & controle , Gordura Intra-Abdominal/irrigação sanguínea , Gordura Intra-Abdominal/metabolismo , Proteínas do Tecido Nervoso/deficiência , Obesidade/metabolismo , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/metabolismo , Adipogenia , Adiposidade , Idoso , Animais , Proteína C-Reativa/genética , Plasticidade Celular , Células Cultivadas , Modelos Animais de Doenças , Feminino , Haplótipos , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/imunologia , Gordura Intra-Abdominal/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Neovascularização Fisiológica , Proteínas do Tecido Nervoso/genética , Obesidade/imunologia , Obesidade/fisiopatologia , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/genética , Obesidade Abdominal/fisiopatologia , Fenótipo , Componente Amiloide P Sérico/genética , Transdução de Sinais , Gordura Subcutânea/imunologia , Aumento de PesoRESUMO
Background: Cell-assisted lipotransfer (CAL) has been considered a promising technique for promoting adipogenesis and angiogenesis in fat grafts. Objectives: The author sought to objectively analyze the change of breast volume in patients who underwent stromal vascular fraction (SVF)-enriched fat grafting for breast augmentation and compared the clinical results with those who underwent conventional fat grafting without SVF by using 3-dimensional laser scanning. Methods: From April 2015 to March 2016, 105 patients who underwent traditional fat grafting without SVF enrichment for breast augmentation were assigned to group A and served as the control. The other 101 patients who underwent SVF-enriched fat grafting for breast augmentation were assigned to group B. The charts of these patients were retrospectively reviewed. Results: The survival rate of the transplanted fat was 67.9% in group A and 68.7% in group B at 12 months after the operation. Postoperative complication rate was 3.8% in group A and 5.9% in group B. The differences were statistically insignificant. Conclusions: SVF does not ensure a higher survival rate in autologous fat grafting for breast augmentation. Considering the potential drawbacks of adipose-derived stem cells (ADSC) and the extra cost of the consumables, in particular the need for harvesting larger amount of fat which could be reserved for additional fat grafting at a later time to achieve even better improvement, the results of this study do not support the use of SVF in autologous fat grafting for breast augmentation in terms of graft survival and postoperative complications.
Assuntos
Sobrevivência de Enxerto , Mamoplastia/métodos , Tamanho do Órgão , Complicações Pós-Operatórias/epidemiologia , Gordura Subcutânea/transplante , Adulto , Mama/anatomia & histologia , Mama/diagnóstico por imagem , Mama/cirurgia , Feminino , Seguimentos , Humanos , Imageamento Tridimensional/instrumentação , Lasers , Lipectomia/métodos , Mamoplastia/efeitos adversos , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Células Estromais/transplante , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/citologia , Transplante Autólogo/métodos , Resultado do Tratamento , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: External volume expansion improves the survival of adipose tissue grafts by preoperatively conditioning ("preconditioning") tissues that will receive the graft. External volume expansion's mechanisms of action (induction of angiogenesis and of adipogenesis) could improve graft survival also when applied postoperatively ("postconditioning"). METHODS: Fifty-six 8-week-old athymic (nu/nu) mice received dorsal subcutaneous grafts of human lipoaspirate (0.3 ml each) bilaterally before undergoing external volume expansion (left dorsum) or no treatment (right dorsum, controls). External volume expansion was started either on the same day of (immediate group), 2 days after (early group), or 1 week after surgery (delayed group). At follow-up, grafts were analyzed for tissue survival, remodeling, adipogenesis, and angiogenesis using histology. The authors subsequently assessed the effects of the delayed application of external volume expansion adopting a foam-shaped interface to deliver the treatment. RESULTS: At 28-day follow-up, delayed postconditioning with external volume expansion significantly improved the survival of grafts (18 percent) compared with controls (viable graft thickness ratio, 58 ± 15 percent versus 49 ± 13 percent) and increased the density of blood vessels within the graft (63 percent; blood vessels per 10× magnification field, 44 ± 12 versus 27 ± 11). Other groups did not experience significant changes. Adoption of external volume expansion with a foam-shaped interface similarly improved outcomes and further reduced fibrosis within the grafts. CONCLUSIONS: Postoperative delayed application of external volume expansion modestly improves the survival of adipose tissue grafts by inducing adipogenesis and angiogenesis. Use of a foam-shaped interface decreases the fibrosis induced in the grafts.
Assuntos
Tecido Adiposo/transplante , Sobrevivência de Enxerto/fisiologia , Pós-Condicionamento Isquêmico/métodos , Gordura Subcutânea/transplante , Tecido Adiposo/irrigação sanguínea , Animais , Modelos Animais de Doenças , Feminino , Seguimentos , Camundongos , Camundongos Nus , Neovascularização Fisiológica , Distribuição Aleatória , Valores de Referência , Gordura Subcutânea/irrigação sanguínea , Fatores de Tempo , Expansão de Tecido/métodos , Transplante de Tecidos/efeitos adversos , Transplante de Tecidos/métodosRESUMO
OBJECTIVE: Tetrahydrobiopterin (BH4) is the essential cofactor of endothelial nitric oxide synthase (eNOS) and intracellular levels of BH4 is regulated by oxidative stress. The aim of this paper was to describe the influence of exogenous endothelin-1 on intracellular BH4 and its oxidation products dihydrobiopterin (BH2) and biopterin (B) in a wide range of vascular tissue. DESIGN: Segments of internal mammary artery (IMA) and human saphenous vein (SV) from 41 patients undergoing elective surgery were incubated in ET-1 (0.1 µM). Aorta and lung from transgenic mice overexpressing ET-1 in the endothelium (ET-TG) were analysed with regards to intracellular biopterin levels. Human umbilical vein endothelial cells (HUVEC) were incubated in ET-1 (0.1 µM) and intracellular biopterin levels were analysed. From 6 healthy women undergoing caesarean section, subcutaneous fat was harvested and the resistance arteries in these biopsies were tested for ET-mediated endothelial dysfunction. RESULTS: In HUVEC, exogenous ET-1 (0.1 µM) did not significantly change intracellular BH4, 1.54 ± 1.7 vs 1.68 ± 1.8 pmol/mg protein; p = .8. In IMA and SV, exogenous ET-1(0.1 µM) did not change intracellular BH4 n = 10, p = .4. In aorta from wild type vs ET-TG mice there was no significant difference in intracellular BH4 between the groups: 1.3 ± 0.49 vs 1.23 ± 0.3 pmol/mg protein; p = .6. In resistance arteries (n = 6) BH4 together with DTE (an antioxidant) was not able to prevent ET-mediated endothelial dysfunction. CONCLUSION: ET-1 did not significantly alter intracellular tetrahydrobiopterin levels in IMA, SV, HUVEC or aorta from ET-TG mice. These findings are important for future research in ET-1 mediated superoxide production and endothelial dysfunction.
Assuntos
Biopterinas/análogos & derivados , Endotelina-1/farmacologia , Artéria Torácica Interna/efeitos dos fármacos , Veia Safena/efeitos dos fármacos , Gordura Subcutânea/irrigação sanguínea , Idoso , Animais , Antioxidantes/farmacologia , Aorta/metabolismo , Biopterinas/metabolismo , Linhagem Celular , Endotelina-1/genética , Endotelina-1/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Pulmão/metabolismo , Masculino , Artéria Torácica Interna/metabolismo , Camundongos Transgênicos , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III , Gravidez , Veia Safena/metabolismo , Superóxidos/metabolismo , Técnicas de Cultura de Tecidos , Vasodilatação/efeitos dos fármacosRESUMO
BACKGROUND: The evaluation of the morphological characteristics of small resistance arteries in humans is challenging. The gold standard method is generally considered to be the measurement by wire or pressure micromyography of the media-to-lumen ratio of subcutaneous small vessels obtained by local biopsies. However, noninvasive techniques for the evaluation of retinal arterioles were recently proposed; in particular, two approaches, scanning laser Doppler flowmetry (SLDF) and adaptive optics, seem to provide useful information; both of them provide an estimation of the wall-to-lumen ratio (WLR) of retinal arterioles. Moreover, a noninvasive measurement of basal and total capillary density may be obtained by videomicroscopy/capillaroscopy. No direct comparison of these three noninvasive techniques in the same population was previously performed; in particular, adaptive optics was never validated against micromyography. METHODS: In the current study, we enrolled 41 controls and patients: 12 normotensive lean controls, 12 essential hypertensive lean patients, nine normotensive obese patients and eight hypertensive obese patients undergoing elective surgery. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance artery structure was assessed by wire micromyography and the media-to-lumen ratio was calculated. WLR of retinal arterioles was obtained by SLDF and adaptive optics. Functional (basal) and structural (total) microvascular density was evaluated by capillaroscopy before and after venous congestion. RESULTS AND CONCLUSION: Our data suggest that adaptive optics has a substantial advantage over SLDF in terms of evaluation of microvascular morphology, as WLR measured with adaptive optics is more closely correlated with the M/L of subcutaneous small arteries (râ=â0.84, Pâ<â0.001 vs. râ=â0.52, Pâ<â0.05, slopes of the relations: Pâ<â0.01 adaptive optics vs. SLDF). In addition, the reproducibility of the evaluation of the WLR with adaptive optics is far better, as compared with SLDF, as intraobserver and interobserver variation coefficients are clearly smaller. This may be important in terms of clinical evaluation of microvascular morphology in a clinical setting, as micromyography has substantial limitations in its clinical application due to the local invasiveness of the procedure.
Assuntos
Arteríolas/diagnóstico por imagem , Hipertensão Essencial/diagnóstico por imagem , Fluxometria por Laser-Doppler/métodos , Angioscopia Microscópica , Imagem Óptica/métodos , Vasos Retinianos/diagnóstico por imagem , Adulto , Idoso , Artérias/fisiopatologia , Arteríolas/patologia , Biópsia , Pressão Sanguínea , Hipertensão Essencial/complicações , Hipertensão Essencial/patologia , Feminino , Humanos , Masculino , Microscopia de Vídeo , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico por imagem , Obesidade/patologia , Reprodutibilidade dos Testes , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/patologia , Magreza/complicações , Magreza/diagnóstico por imagem , Magreza/patologiaRESUMO
First described in 1959, intravascular lymphoma (IVL) remains one of the most clinically challenging diagnoses due to its diverse and non-specific clinical manifestations and evasiveness in detection by standard investigations. Indeed, IVL deserves the title of 'medicine's greatest imitator'. We highlight a case of IVL where the diagnosis came too late in the clinical course, detected by random skin biopsy. Clinicians should strongly consider this diagnosis in presentations with persistent symptomatology despite appropriate interventions.
Assuntos
Fluxo Sanguíneo Regional/fisiologia , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/patologia , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/fisiopatologia , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Diagnóstico Diferencial , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/fisiopatologiaRESUMO
BACKGROUND: Small artery pathophysiology is frequently invoked as a cause of obesity-related diastolic heart failure. However, evidence to support this hypothesis is scant, particularly in humans. METHODS AND RESULTS: To address this, we studied human small artery structure and function in obesity and looked for correlations between vascular parameters and diastolic function. Seventeen obese patients with metabolic syndrome and 5 control participants underwent echocardiography and subcutaneous gluteal fat biopsy. Small arteries were isolated from the biopsy and pressure myography was used to study endothelial function and wall structure. In comparison with the control group, small arteries from obese participants exhibited significant endothelial dysfunction, assessed as the vasodilatory response to acetylcholine and also pathological growth of the wall. For the obese participants, multiple regression analysis revealed an association between left atrial volume and both the small artery wall thickness (ß=0.718, P=0.02) and wall-to-lumen ratio (ß=0.605, P=0.02). Furthermore, the E:E' ratio was associated with wall-to-lumen ratio (ß=0.596, P=0.02) and inversely associated with interleukin-6 (ß=-0.868, P=0.03). By contrast, endothelial function did not correlate with any of the echocardiographic parameters studied. CONCLUSIONS: Although the small arteries studied were not cardiac in origin, our results support a role for small artery remodeling in the development of diastolic dysfunction in humans. Further direct examination of the structure and function of the myocardial resistance vasculature is now warranted, to elucidate the temporal association between metabolic risk factors, small artery injury, and diastolic impairment.
Assuntos
Artérias/fisiopatologia , Síndrome Metabólica/fisiopatologia , Obesidade/fisiopatologia , Gordura Subcutânea/irrigação sanguínea , Remodelação Vascular , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Adulto , Idoso , Artérias/patologia , Biópsia , Nádegas , Estudos de Casos e Controles , Diástole , Ecocardiografia Doppler , Humanos , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Obesidade/diagnóstico , Fatores de Risco , Vasodilatação , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
Body fat accumulation, distribution, and metabolic activity are factors in the pathophysiology of obesity and type 2 diabetes (T2D). We investigated adipose blood flow, fatty acid uptake (FAU), and subcutaneous and visceral fat cellularity in obese patients with or without T2D. A total of 23 morbidly obese (mean body mass index = 42 kg/m2) patients were studied before and 6 mo after bariatric surgery; 15 nonobese subjects served as controls. Positron emission tomography was used to measure tissue FAU (with 18F-FTHA) and blood flow (with H215O); MRI was used for fat distribution and fat biopsy for adipocyte size. Obese subjects had subcutaneous hyperplasia and hypertrophy and lower blood flow; when expressed per cell, flow was similar to controls. FAU into subcutaneous and visceral depots was increased in the obese; per unit tissue mass, however, FAU was similar to controls but reduced in skeletal muscle. Fatty acid fractional extraction in subcutaneous fat and muscle was only increased in obese patients with T2D. We conclude that surgery reduces subcutaneous fat hyperplasia and hypertrophy; subcutaneous blood flow and FAU decrease in absolute terms and per cell while fractional FAU remains unchanged in T2D. In the obese, subcutaneous blood flow is a determinant of FAU and is coupled with cellularity; efficiency of FAU is enhanced in subcutaneous fat and muscle in T2D.
Assuntos
Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/metabolismo , Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Ácidos Graxos/metabolismo , Obesidade Mórbida , Fluxo Sanguíneo Regional , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo/patologia , Adiposidade , Adulto , Distribuição da Gordura Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Gordura Intra-Abdominal/irrigação sanguínea , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Metabolismo dos Lipídeos , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/metabolismo , Gordura Subcutânea/patologiaRESUMO
Adipocyte-derived vascular endothelial growth factor-A (VEGF-A) plays a crucial role in angiogenesis and contributes to adipocyte function and systemic metabolism, such as insulin resistance, chronic inflammation, and beiging of subcutaneous adipose tissue. Using a doxycycline-inducible adipocyte-specific VEGF-A-overexpressing mouse model, we investigated the dynamics of local VEGF-A effects on tissue beiging of adipose tissue transplants. VEGF-A overexpression in adipocytes triggers angiogenesis. We also observed a rapid appearance of beige fat cells in subcutaneous white adipose tissue as early as 2 days postinduction of VEGF-A. In contrast to conventional cold-induced beiging, VEGF-A-induced beiging is independent of interleukin-4. We subjected metabolically healthy VEGF-A-overexpressing adipose tissue to autologous transplantation. Transfer of subcutaneous adipose tissues taken from VEGF-A-overexpressing mice into diet-induced obese mice resulted in systemic metabolic benefits, associated with improved survival of adipocytes and a concomitant reduced inflammatory response. These effects of VEGF-A are tissue autonomous, inducing white adipose tissue beiging and angiogenesis within the transplanted tissue. Our findings indicate that manipulation of adipocyte functions with a bona fide angiogenic factor, such as VEGF-A, significantly improves the survival and volume retention of fat grafts and can convey metabolically favorable properties on the recipient on the basis of beiging.
Assuntos
Adipócitos Bege/metabolismo , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Branco/metabolismo , Diferenciação Celular/genética , Neovascularização Fisiológica/genética , Obesidade/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adipócitos Bege/citologia , Tecido Adiposo/metabolismo , Tecido Adiposo/transplante , Tecido Adiposo Bege/irrigação sanguínea , Tecido Adiposo Bege/citologia , Tecido Adiposo Branco/irrigação sanguínea , Tecido Adiposo Branco/citologia , Animais , Diferenciação Celular/imunologia , Imunofluorescência , Teste de Tolerância a Glucose , Interleucina-4/imunologia , Camundongos , Reação em Cadeia da Polimerase , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/citologia , Gordura Subcutânea/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Fusion zones between superficial fascia and deep fascia have been recognized by surgical anatomists since 1938. Anatomical dissection performed by the author suggested that additional superficial fascia fusion zones exist. OBJECTIVES: A study was performed to evaluate and define fusion zones between the superficial and the deep fascia. METHODS: Dissection of fresh and minimally preserved cadavers was performed using the accepted technique for defining anatomic spaces: dye injection combined with cross-sectional anatomical dissection. RESULTS: This study identified bilaminar membranes traveling from deep to superficial fascia at consistent locations in all specimens. These membranes exist as fusion zones between superficial and deep fascia, and are referred to as SMAS fusion zones. CONCLUSIONS: Nerves, blood vessels and lymphatics transition between the deep and superficial fascia of the face by traveling along and within these membranes, a construct that provides stability and minimizes shear. Bilaminar subfascial membranes continue into the subcutaneous tissues as unilaminar septa on their way to skin. This three-dimensional lattice of interlocking horizontal, vertical, and oblique membranes defines the anatomic boundaries of the fascial spaces as well as the deep and superficial fat compartments of the face. This information facilitates accurate volume augmentation; helps to avoid facial nerve injury; and provides the conceptual basis for understanding jowls as a manifestation of enlargement of the buccal space that occurs with age.
Assuntos
Envelhecimento , Fáscia/anatomia & histologia , Gordura Subcutânea/anatomia & histologia , Gordura Subcutânea/cirurgia , Tela Subcutânea/anatomia & histologia , Tela Subcutânea/cirurgia , Sistema Musculoaponeurótico Superficial/anatomia & histologia , Sistema Musculoaponeurótico Superficial/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cadáver , Dissecação , Fáscia/irrigação sanguínea , Fáscia/inervação , Fasciotomia , Feminino , Humanos , Vasos Linfáticos/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/inervação , Tela Subcutânea/irrigação sanguínea , Tela Subcutânea/inervação , Sistema Musculoaponeurótico Superficial/irrigação sanguínea , Sistema Musculoaponeurótico Superficial/inervaçãoRESUMO
Although more fat grafting procedures have been performed by plastic surgeons with the primary goal to restore soft tissue loss, the actual mechanism on how fat graft survives remains less completely understood. An established old theory on fat graft survival is still based on the cell survival theory proposed by Peer in the early 1950s. On the basis of his preliminary experimental study, he proposed that the mechanism of fat graft survival is based on established early blood circulation through anastomosis of the fat graft and host blood vessels. Recently, several investigators have demonstrated new concepts of the fat graft survival: One further advanced the old Peer cell survival theory and another based on new discovery and understanding of adipose-derived stem cells. This article serves as a scientific review on how fat graft survives after in vivo transplantation based on a number of well-conducted experimental studies. Both the graft survival and graft replacement theories on how fat graft survives are true based on the previously mentioned well-conducted experimental studies. Each theory may play a role in fat graft survival. It is possible that graft survival may be more dominant in some patients but the graft replacement may be more dominant in other patients.
Assuntos
Sobrevivência de Enxerto/fisiologia , Procedimentos de Cirurgia Plástica/métodos , Gordura Subcutânea/transplante , Sobrevivência Celular/fisiologia , Humanos , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/fisiologia , Transplante AutólogoRESUMO
Obesity and its metabolic complications are one of the most profound public health problems and result from interactions between genes and environmental. The development of obesity is tightly connected with dysregulation of intrinsic gene expression mechanisms controlling majority of metabolic processes, which are essential for regulation many physiological functions, including insulin sensitivity, cellular proliferation and angiogenesis. Our objective was to evaluate if expression of angiogenesis related genes VEGF-A, CYR61, PDGFC, FGF1, FGF2, FGFR2, FGFRL1, E2F8, BAI2, HIF1A, and EPAS1 at mRNA level in adipose tissue could participate in the development of obesity and metabolic complications. We have shown that expression level of VEGF-A, PDGFC, FGF2, and FGFRL1 genes is decreased in adipose tissue of obese men with normal glucose tolerance (NGT) versus a group of control subjects. At the same time, in this group of obese individuals a significant up-regulation of CYR61, FGF1, FGFR2, E2F8, BAI2, and HIF1A gene expressions was observed. Impaired glucose tolerance (IGT) in obese patients associates with down-regulation of CYR61 and FGFR2 mRNA and up-regulations of E2F8, FGF1, FGF2, VEGF-A and its splice variant 189 mRNA expressions in adipose tissue versus obese (NGT) individuals. Thus, our data demonstrate that the expression of almost all studied genes is affected in subcutaneous adipose tissue of obese individuals with NGT and that glucose intolerance is associated with gene-specific changes in the expression of E2F8, FGF1, FGF2, VEGF-A, CYR61 and FGFR2 mRNAs. The data presented here provides evidence that VEGF-A, CYR61, PDGFC, FGF1, FGF2, FGFR2, FGFRL1, E2F8, BAI2, and HIF1A genes are possibly involved in the development of obesity and its complications.
Assuntos
Regulação da Expressão Gênica , Intolerância à Glucose/genética , Glucose/metabolismo , Neovascularização Patológica/genética , Obesidade/genética , Gordura Subcutânea/metabolismo , Adulto , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Estudos de Casos e Controles , Proteína Rica em Cisteína 61/genética , Proteína Rica em Cisteína 61/metabolismo , Fator 1 de Crescimento de Fibroblastos/genética , Fator 1 de Crescimento de Fibroblastos/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Teste de Tolerância a Glucose , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Insulina/metabolismo , Resistência à Insulina , Linfocinas/genética , Linfocinas/metabolismo , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: The aim of this study was to examine volumetric changes in fat flaps after stresses as well as their relationship with capillary density (CD) in a Zucker fatty rat model. METHODS: A total of 12 male Zucker-fa/fa rats were randomly divided into two stress groups. Superficial epigastric fat flaps were evaluated on the right side as control and on the left side as the stress (ischemic or congestive) condition in the same rat in order to avoid biases. Stress conditions were made by obstructing the pedicle vessels with a vascular clip for 3 hours. The volumes of these flaps were measured weekly. After 12 weeks of measurements, the CD of harvested flaps was examined in histologically immunostained sections. Percent changes in the body-weight-corrected flap volume [cFV(%)], the stress/control ratio [FV-ratio(%)], and the stress/control ratio of CD (CD-ratio) were defined. RESULTS: cFV(%) 12 weeks after surgery was 34.7 ± 26.7 in the control flaps and 13.2 ± 10.5 in the stress flaps. The FV-ratio(%) after 12 weeks was 7.4-202.5 (70.2 ± 77.9) in the ischemic group and 14.6-66.3 (37.7 ± 22.2) in the congestive group. The difference in variance between two groups was significant (P = 0.030). cFV(%) correlated with total CD (P = 0.011). The FV-ratio(%) correlated with the CD-ratio (P = 0.002). CONCLUSIONS: Weekly measurements of flap volumes in the Zucker fatty rat model were new and useful methods. The FV-ratio(%) in the congestive group decreased at a constant rate, while that in the ischemic group decreased or increased slightly. The rate of decreases in the flap volume correlated with CD.
Assuntos
Capilares/patologia , Isquemia/etiologia , Complicações Pós-Operatórias , Gordura Subcutânea/transplante , Retalhos Cirúrgicos/irrigação sanguínea , Animais , Capilares/diagnóstico por imagem , Isquemia/diagnóstico por imagem , Isquemia/patologia , Masculino , Modelos Animais , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Distribuição Aleatória , Ratos , Ratos Zucker , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/patologia , Retalhos Cirúrgicos/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: This study evaluated the in vitro effects of hydrogen sulfide on adipocyte survival under ischemic conditions and explored possible mechanisms of its apoptotic process. METHODS: The mesenchymal stem cell culture was prepared from a human subcutaneous adipose tissue sample. Adipose-derived mesenchymal stem cells were differentiated into the adipogenic direction, and a mature adipocyte culture was obtained. The adipose-derived mesenchymal stem cell and mature adipocyte cultures were both divided into 6 groups. Sodium hydrogen sulfide was used as a hydrogen sulfide donor. After treating the groups with sodium hydrogen sulfide (0, 0.1, 1, 10, 100, and 1000 µM), the cell cultures were incubated in 1% oxygen at 37°C for 24 hours. After the ischemia period, the cell culture groups were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test for the proliferation/cytotoxicity rates, flow cytometry for apoptosis and necrosis rates, and reverse transcriptase polymerase chain reaction for apoptotic (Bax, Caspase-3) and antiapoptotic (Bcl-2) gene expression levels. RESULTS: Statistically significant increases in proliferation rates were found in mesenchymal stem cell groups treated with low dose (0, 1, and 1 µM) sodium hydrogen sulfide (P<0.05). For each dose, a statistically significant decrease was found in late apoptosis levels on the mature adipocyte cultures (P<0.05). In both cell culture groups, Bcl-2 gene expression was increased and Caspase-3 gene expression was decreased. CONCLUSIONS: Under ischemic conditions, hydrogen sulfide has a protective effect on mesenchymal stem cells and mature adipocytes, and this effect is mediated by the elevation of antiapoptotic gene expression.
Assuntos
Adipócitos/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Isquemia/tratamento farmacológico , Células-Tronco Mesenquimais/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Gordura Subcutânea/irrigação sanguínea , Adipócitos/fisiologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Sulfeto de Hidrogênio/uso terapêutico , Isquemia/fisiopatologia , Células-Tronco Mesenquimais/fisiologia , Substâncias Protetoras/uso terapêutico , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/fisiologiaRESUMO
BACKGROUND: Variable results associated with fat grafting have been attributed to local trauma, inconsistencies in transfer, and ischemia before the development of recipient circulation. Remote ischemic preconditioning is an inexpensive noninvasive technique that has been used in animal models and multicenter clinical trials to protect organ systems. In this work, the authors describe a novel animal model for analyzing the efficacy of fat grafting, and investigate the effect of remote ischemic preconditioning on volume retention. METHODS: Subcutaneous adipose tissue samples from green fluorescent protein/luciferase-expressing FVB mice were obtained with or without pretreatment with a temporary hind-limb tourniquet. The samples were injected into the dorsal skin folds of wild-type FVB mice. The viability of the transferred tissue was examined over a 28-day period with quantitative bioluminescence after luciferin injection. Transferred tissue was also explanted for histologic analysis. RESULTS: The remote ischemic preconditioning group had significantly increased bioluminescence at days 0, 1, and 28. Histologic analysis at day 28 confirmed the presence of vascularized adipose in both groups. However, significant amounts of interstitial fibrosis were found in the control group, whereas substantially less was found in the remote ischemic preconditioning group. The remote ischemic preconditioning group retained a substantially greater amount of green fluorescent protein, suggesting increased survival of donor adipocytes. CONCLUSIONS: In this work, the authors describe a novel animal model for quantitative evaluation of fat grafting using in vivo bioluminescence of adipocytes from luciferase-expressing mice. The authors also demonstrate that remote ischemic preconditioning increases the viability of fat transfer and decreases interstitial fibrosis.