RESUMO
BACKGROUND: This study aimed to investigate the influence of abdominal aortic calcification on the distal extent, blood supply, and mid-term outcomes of acute aortic dissection (AAD). METHODS: This single-centre retrospective study was conducted from August 2014 to May 2021. The aortic calcification index was used to evaluate abdominal aortic calcification. The standardized method provided by the Society for Vascular Surgery was used to evaluate the distal extent of AAD. Patients were divided into 3 groups as per the degree of calcification: no calcification (NC), low calcification (LC), and high calcification (HC). RESULTS: In a cohort of 723 patients, abdominal aortic calcification was present in 424 (58.6%) patients. The prevalence of coronary heart disease increased with the degree of calcification (NC versus LC versus HC: 8.4% vs. 9.5% vs. 19.3%, P < 0.001). The aortic calcification index of the distal extent at zone 9 was higher than that of the distal extent exceeding zone 9 (P = 0.001). The proportions of the NC, LC, and HC groups with distal extents exceeding zone 9 were 65.9% vs. 56.2% vs. 37.7%, P < 0.001. In a multivariate logistics analysis, the calcification grade was a protective factor of distal extents exceeding zone 9 (P < 0.001, odds ratio [OR] = 0.592). Hypertension (P = 0.019, OR = 1.559) and D-dimer (P < 0.001, OR = 1.045) were risk factors. There was a higher proportion of branch-vessels on the abdominal aorta supplied by the true lumen in the calcification group (NC versus LC versus HC: 27.8% vs. 43.8% vs. 51.1%, P < 0.001). There were no significant differences in the mid-term outcomes among the groups. CONCLUSIONS: Abdominal aortic calcification could limit the distal extent in patients with AAD and increase the proportion of branch-vessels on the abdominal aorta supplied by the true lumen.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Arteriosclerose , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Dissecção Aórtica/etiologia , Arteriosclerose/etiologia , Procedimentos Cirúrgicos Vasculares , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversosRESUMO
BACKGROUND: Graft vascular disease (GVD) is the main reason of late transplanted organ failure, which limits the long-term survival of patients. Murine aortic transplant is widely used in the field to understand the mechanisms leading to GVD. Currently, 3 major techniques, end-to-end anastomosis, sleeve suture and cuff technology, have been used to study the mechanism of GVD. However, which method is more suitable in mouse model of GVD? Herein, we compared these 3 surgical techniques in a mouse allograft arteriosclerosis model to determine the technique with the most appreciable outcomes. METHODS: Male C57Bl/6 (H-2b) and BALB/c (H-2d) mice were used for aorta transplantation with these 3 techniques. These 3 techniques were compared with regard to donor artery acquisition time, artery anastomosis time, overall surgical time, the amount of bleeding of each technique and the success rate of surgery. Hematoxylin and eosin (H&E) and Masson staining were used to examine the pathological changes of grafted vessels. The protein expression of phospho-NF-κb P65 and PCNA were determined to validate laminar flow and proliferative capacity of neointima obtained from different surgical and control groups. RESULTS: Sleeve suture had a shorter vascular anastomosis time and total operation time than end-to-end anastomosis and cuff technique. Sleeve suture and cuff technique had significantly fewer amount of bleeding from the site of vascular anastomosis than end-to-end anastomosis. Moreover, sleeve suture had the highest success rate among these 3 techniques. There was no difference in the degree of graft stenosis and collagen deposition between these 3 techniques. In addition, there was no significant difference in the expression of phospho-NF-κb P65and PCNA between the experimental group. CONCLUSIONS: Sleeve suture is superior to end-to-end anastomosis and cuff technique with regard to vascular grafting in the murine model.
Assuntos
Aorta Abdominal/transplante , Doenças da Aorta/etiologia , Arteriosclerose/etiologia , Enxerto Vascular/métodos , Anastomose Cirúrgica , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Arteriosclerose/metabolismo , Arteriosclerose/patologia , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neointima , Fosforilação , Antígeno Nuclear de Célula em Proliferação/metabolismo , Fatores de Tempo , Fator de Transcrição RelA/metabolismoRESUMO
Fundamental pancreatic ß-cell function is to produce and secrete insulin in response to blood glucose levels. However, when ß-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic ß-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the ß-cell membrane and thereby enhances insulin secretion, suppresses apoptotic cell death and increase proliferation of ß-cells. However, GLP-1R expression in ß-cells is reduced under diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable effects on ß-cells at an early stage of T2DM compared to an advanced stage. On the other hand, it has been drawing much attention to the idea that GLP-1 signaling is important in arterial cells; GLP-1 increases nitric oxide, which leads to facilitation of vascular relaxation and suppression of arteriosclerosis. However, GLP-1R expression in arterial cells is also reduced under diabetic conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at an early stage of T2DM. Furthermore, it has been reported recently that administration of GLP-1RA leads to the reduction of cardiovascular events in various large-scale clinical trials. Therefore, we think that it would be better to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis and protection of ß-cells against glucose toxicity in routine medical care.
Assuntos
Arteriosclerose/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hiperglicemia/complicações , Incretinas/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Arteriosclerose/etiologia , Arteriosclerose/prevenção & controle , Humanos , Incretinas/farmacologia , Células Secretoras de Insulina/fisiologiaRESUMO
Vascular, resident stem cells are present in all 3 layers of the vessel wall; they play a role in vascular formation under physiological conditions and in remodeling in pathological situations. Throughout development and adult early life, resident stem cells participate in vessel formation through vasculogenesis and angiogenesis. In adults, the vascular stem cells are mostly quiescent in their niches but can be activated in response to injury and participate in endothelial repair and smooth muscle cell accumulation to form neointima. However, delineation of the characteristics and of the migration and differentiation behaviors of these stem cells is an area of ongoing investigation. A set of genetic mouse models for cell lineage tracing has been developed to specifically address the nature of these cells and both migration and differentiation processes during physiological angiogenesis and in vascular diseases. This review summarizes the current knowledge on resident stem cells, which has become more defined and refined in vascular biology research, thus contributing to the development of new potential therapeutic strategies to promote endothelial regeneration and ameliorate vascular disease development.
Assuntos
Arteriosclerose/etiologia , Vasos Sanguíneos/citologia , Neovascularização Fisiológica , Células-Tronco/fisiologia , Adulto , Animais , Arteriosclerose/prevenção & controle , Movimento Celular , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Camundongos , Modelos Animais , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/fisiologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/fisiologia , Neointima/etiologia , Neointima/patologia , Células-Tronco/citologia , Doenças Vasculares/etiologia , Doenças Vasculares/prevenção & controle , Remodelação Vascular/fisiologiaRESUMO
BACKGROUND: Replicative senescence is associated with telomere shortening. In native kidneys, obtained prior to transplantation, we recently described and validated a significant association between shorter intrarenal telomere length and renal arteriosclerosis. After renal transplantation, animal experiments suggested that ischaemia-reperfusion injury, acute rejection episodes and cytomegalovirus disease associate with accelerated renal allograft senescence. The association between post-transplant events and replicative senescence has not yet been evaluated in a human setting. METHODS: In a cohort of 134 kidney allograft recipients, we performed protocol-specified renal allograft biopsies at 3 months, 1 year, 2 years and 5 years after transplantation (n = 579 biopsies). We used quantitative real-time polymerase chain reaction to measure intrarenal relative average telomere length (T/S ratio). The association between donor and recipient demographic factors, post-transplant clinical/histological events, renal allograft histological evolution by 5 years post-transplant and intrarenal telomere length at 5 years after transplantation was studied using multiple regression models. RESULTS: At 5 years after transplantation, shorter intrarenal telomere length was associated with male donor gender, older donor age, donor history of hypertension and donor cardiovascular risk, which confirms the associations observed in native kidneys. Recipient characteristics and post-transplant events like delayed graft function, acute rejection episodes, presence of donor-specific antibodies, cytomegalovirus disease and immunosuppressive regimen did not associate with alterations of intrarenal telomere length at 5 years. Independent of donor age and donor cardiovascular risk, intrarenal arteriosclerosis in protocol biopsies obtained at 5 years after transplantation and progressive arteriosclerosis over time after transplantation associated with shorter telomere length, while this was not the case for other histological lesions. Moreover, telomere attrition augments the association between older donor age and the presence of severe arteriosclerosis. In the group with the oldest donor age and shortest telomere length, there was significantly more severe arteriosclerosis (43%) in protocol biopsies at 5 years after transplantation, compared with other combinations (13-28%) (P = 0.001). Intrarenal arteriosclerosis at 5 years after transplantation did not associate with post-transplant clinical events. CONCLUSIONS: We demonstrate that intrarenal telomere length at 5 years after transplantation, as a marker for replicative senescence, associates with renal arteriosclerosis and reflects kidney donor characteristics, but not post-transplant events.
Assuntos
Arteriosclerose/patologia , Senescência Celular , Rejeição de Enxerto/patologia , Transplante de Rim/efeitos adversos , Rim/patologia , Telômero , Adulto , Arteriosclerose/etiologia , Feminino , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doadores de Tecidos , Transplante HomólogoRESUMO
Preventing cardiovascular disease (CVD) is an urgent public health challenge. Although brachial-ankle pulse wave velocity (baPWV) can indicate the risk of arterial stiffness and CVD, findings regarding whether baPWV is associated with smoking are inconsistent. This study considered the influence of smoking on arteriosclerosis, specifically focusing on secondhand smoke (SHS), and aimed to construct a strategy for preventing the worsening of arteriosclerosis. We recruited 295 male employees from five companies who had smoking habits such as being smokers, living with smokers, and exposure to SHS outside the home. We measured body composition and hemodynamics, including blood pressure and baPWV, and found that baPWV had significant positive correlations with age, smoking index, alcohol consumption, body-fat percentage, blood pressure, and heart rate, and significant negative correlations with height, fat-free mass, and lower-limb muscle mass. Moreover, baPWV showed a significant adverse effect on participants who had metabolic syndrome (MetS) risk factors such as hypertension, dyslipidemia, and diabetes. Multiple regression analysis showed that baPWV had significant positive relationships with age, height, MetS risk factors, cohabitation with smokers, blood pressure, and heart rate, and a significant negative relationship with lower-limb muscle mass. The same results were obtained when adjusting for current smoking status, smoking index, cohabitation with smokers at birth, and frequency of exposure to SHS outside the home. Exposure to tobacco smoke due to cohabitation with smokers increased baPWV regardless of the person's smoking habits. Thus, to prevent an increase in baPWV in housemates and smokers, it is necessary for smokers to quit smoking.
Assuntos
Arteriosclerose/etiologia , Arteriosclerose/prevenção & controle , Saúde Ocupacional , Características de Residência , Fumantes , Poluição por Fumaça de Tabaco/efeitos adversos , Rigidez Vascular , Local de Trabalho , Arteriosclerose/fisiopatologia , Progressão da Doença , Humanos , Masculino , Análise de Onda de Pulso , Fatores de Risco , Abandono do Hábito de FumarRESUMO
It is difficult to detect glycemic excursions using CGM in daily clinical practice. We retrospectively analyzed CGM data in type T2DM to define the correlations between HbA1c and GA levels at admission and the parameters representing glycemic excursions measured by CGM, including the mean amplitude of glycemic excursions (MAGE) and standard deviation (SD). The MAGE correlated significantly with GA and HbA1c, but not with the GA/HbA1c ratio. The SD correlated significantly with GA, HbA1c, and GA/HbA1c. Multivariate analysis identified the GA value to be the most reflective of MAGE. Patients were divided into 2 groups using a MAGE cutoff value of 75 mg/dl, which reflects stable diabetes. There was a significant difference in GA, but not HbA1c, between the groups with low and high mean amplitudes of glycemic excursions. Receiver operating characteristic curve analysis indicated that the cutoff for GA for identifying patients with MAGE of ≤75 mg/dl was 18.1%. Our study identified GA to be the most reflective of glycemic excursions in patients with T2DM. GA can be a useful index of glycemic excursions and treatment optimization to prevent arteriosclerosis.
Assuntos
Automonitorização da Glicemia/métodos , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/análise , Índice Glicêmico , Albumina Sérica/análise , Arteriosclerose/etiologia , Arteriosclerose/prevenção & controle , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Produtos Finais de Glicação Avançada , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Albumina Sérica GlicadaRESUMO
It is unclear whether structural findings in the kidneys of living kidney donors predict postdonation kidney function. We studied living kidney donors who had a kidney biopsy during donation. Nephron size was measured by glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area. Age-specific thresholds were defined for low nephron number (calculated from CT and biopsy measures) and nephrosclerosis (global glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis). These structural measures were assessed as predictors of postdonation measured GFR, 24-hour urine albumin, and hypertension. Analyses were adjusted for baseline age, gender, body mass index, systolic and diastolic blood pressure, hypertension, measured GFR, urine albumin, living related donor status, and time since donation. Of 2673 donors, 1334 returned for a follow-up visit at a median 4.4 months after donation, with measured GFR <60 mL/min/1.73 m2 in 34%, urine albumin >5 mg/24 h in 13%, and hypertension in 5.3%. Larger glomerular volume and interstitial fibrosis/tubular atrophy predicted follow-up measured GFR <60 mL/min/1.73 m2 . Larger cortex volume per glomerulus and low nephron number predicted follow-up urine albumin >5 mg/24 h. Arteriosclerosis predicted hypertension. Microstructural findings predict GFR <60 mL/min/1.73 m2 , modest increases in urine albumin, and hypertension shortly after kidney donation.
Assuntos
Arteriosclerose/patologia , Taxa de Filtração Glomerular , Hipertensão/patologia , Rim/patologia , Doadores Vivos/provisão & distribuição , Néfrons/patologia , Nefroesclerose/patologia , Adulto , Arteriosclerose/etiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Testes de Função Renal , Masculino , Nefrectomia/efeitos adversos , Nefroesclerose/etiologia , Período Pós-Operatório , Prognóstico , Fatores de RiscoRESUMO
Non-alcoholic steatohepatitis (NASH) is linked to increased cardiovascular risk, independent of the broad spectrum of metabolic syndrome risk factors. Stroke-prone (SP) spontaneously hypertensive rats (SHRSP5/Dmcr) fed a high-fat and high-cholesterol (HFC) diet developed hepatic lesions similar to those in human NASH pathology. These rats simultaneously developed lipid deposits in the mesenteric arteries, cardiac fibrosis, endothelial dysfunction and left ventricle (LV) diastolic dysfunction. However, the intermediary factors between NASH and cardiovascular disease are still unknown. We investigated whether NASH aggravates nitric oxide (NO) synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rats. Wistar Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 and fed the stroke-prone (SP) or HFC diets for 8 weeks. To induce NO synthase inhibition, Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME) mixed with drinking water was administered in the final 2 weeks. The NASH+L-NAME group demonstrated the following characteristics related to arteriosclerosis and myocardial ischaemia: (a) LV systolic dysfunction with asynergy, (b) replacement fibrosis caused by the shedding of cardiomyocytes and (c) arterial lipid deposition and coronary occlusion secondary to endothelial dysfunction. These characteristics were not observed in the NASH or non-NASH+L-NAME groups. The SHRSP5/Dmcr rat model demonstrates that NASH significantly aggravates cardiovascular risk.
Assuntos
Arteriosclerose/etiologia , Óxido Nítrico Sintase/antagonistas & inibidores , Hepatopatia Gordurosa não Alcoólica/complicações , Animais , Arteriosclerose/patologia , Arteriosclerose/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Endotélio Vascular/fisiopatologia , Ventrículos do Coração/patologia , Fígado/patologia , Masculino , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , NG-Nitroarginina Metil Éster/farmacologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Tamanho do Órgão , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Renal transplantation can significantly improve the quality of life of patients with end stage renal disease (ESRD) who would otherwise require dialysis. Renal transplant (RT) recipients have higher risks of cardiovascular disease compared with general population. The carotid intima-media thickness (CIMT) and pulse wave velocity (PWV) have been used as the important predicting factor of vascular arteriosclerosis. Therefore, this study was to investigate the improvement of carotid intima-media thickness and pulse wave velocity in renal transplant recipients. METHODS: Thirty-one patients with chronic kidney disease being treated with hemodialysis, 31 renal transplant recipients and 84 healthy control subjects were included to have the clinical evaluations and ultrasonography of bilateral carotid arteries. CIMT and PWV were independently measured by two ultrasonographers using the technique of ultrasonic radiofrequency tracking and correlated with arteriosclerosis risk factors. The progression of CIMT and PWV with age were analyzed by linear regression models, and the slopes of curves were compared using Z test. RESULTS: Compared with the patients on hemodialysis, the CIMT was significantly lower in renal transplant recipients and healthy control. The PWV were higher in hemodialysis patients and renal transplant recipients than that of the subjects in control group. The progression is CIMT positively corelated with age and cumulative duration in renal transplant recipients and hemodialysis patients. In both hemodialysis patients and renal transplant recipients, age and cumulative time on dialysis were all positively correlated with the increase of PWV as well. CONCLUSIONS: Carotid intima-media thickness and pulse wave velocity is the predicting factors of developing arteriosclerosis, which were improved in renal transplant recipients.
Assuntos
Artérias Carótidas/diagnóstico por imagem , Transplante de Rim/métodos , Diálise Renal/métodos , Insuficiência Renal Crônica/terapia , Adulto , Fatores Etários , Idoso , Arteriosclerose/diagnóstico por imagem , Arteriosclerose/etiologia , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Insuficiência Renal Crônica/complicações , Ultrassom/instrumentaçãoAssuntos
Vasos Sanguíneos/metabolismo , Sobrecarga de Ferro/patologia , Ferro/metabolismo , Metais Pesados/metabolismo , Idoso de 80 Anos ou mais , Anemia Sideroblástica/etiologia , Anemia Sideroblástica/patologia , Anemia Sideroblástica/terapia , Arteriosclerose/etiologia , Arteriosclerose/metabolismo , Arteriosclerose/patologia , Biópsia , Transfusão de Sangue , Vasos Sanguíneos/patologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Deferasirox/uso terapêutico , Feminino , Humanos , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/patologia , Doenças Mieloproliferativas-Mielodisplásicas/terapia , Trombocitose/etiologia , Trombocitose/patologia , Trombocitose/terapia , Reação Transfusional/complicações , Reação Transfusional/tratamento farmacológico , Reação Transfusional/patologia , Falha de TratamentoRESUMO
RATIONALE: Wnt signaling regulates key aspects of diabetic vascular disease. OBJECTIVE: We generated SM22-Cre;LRP6(fl/fl);LDLR(-/-) mice to determine contributions of Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6) in the vascular smooth muscle lineage of male low-density lipoprotein receptor-null mice, a background susceptible to diet (high-fat diet)-induced diabetic arteriosclerosis. METHODS AND RESULTS: As compared with LRP6(fl/fl);LDLR(-/-) controls, SM22-Cre;LRP6(fl/fl);LDLR(-/-) (LRP6-VKO) siblings exhibited increased aortic calcification on high-fat diet without changes in fasting glucose, lipids, or body composition. Pulse wave velocity (index of arterial stiffness) was also increased. Vascular calcification paralleled enhanced aortic osteochondrogenic programs and circulating osteopontin (OPN), a matricellular regulator of arteriosclerosis. Survey of ligands and Frizzled (Fzd) receptor profiles in LRP6-VKO revealed upregulation of canonical and noncanonical Wnts alongside Fzd10. Fzd10 stimulated noncanonical signaling and OPN promoter activity via an upstream stimulatory factor (USF)-activated cognate inhibited by LRP6. RNA interference revealed that USF1 but not USF2 supports OPN expression in LRP6-VKO vascular smooth muscle lineage, and immunoprecipitation confirmed increased USF1 association with OPN chromatin. ML141, an antagonist of cdc42/Rac1 noncanonical signaling, inhibited USF1 activation, osteochondrogenic programs, alkaline phosphatase, and vascular smooth muscle lineage calcification. Mass spectrometry identified LRP6 binding to protein arginine methyltransferase (PRMT)-1, and nuclear asymmetrical dimethylarginine modification was increased with LRP6-VKO. RNA interference demonstrated that PRMT1 inhibits OPN and TNAP, whereas PRMT4 supports expression. USF1 complexes containing the histone H3 asymmetrically dimethylated on Arg-17 signature of PRMT4 are increased with LRP6-VKO. Jmjd6, a demethylase downregulated with LRP6 deficiency, inhibits OPN and TNAP expression, USF1: histone H3 asymmetrically dimethylated on Arg-17 complex formation, and transactivation. CONCLUSIONS: LRP6 restrains vascular smooth muscle lineage noncanonical signals that promote osteochondrogenic differentiation, mediated in part via USF1- and arginine methylation-dependent relays.
Assuntos
Arteriosclerose/prevenção & controle , Calcinose/prevenção & controle , Diabetes Mellitus Experimental/complicações , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/fisiologia , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Receptores de LDL/deficiência , Via de Sinalização Wnt , Animais , Arginina/análogos & derivados , Arginina/metabolismo , Arteriosclerose/etiologia , Arteriosclerose/metabolismo , Calcinose/etiologia , Calcinose/metabolismo , Diabetes Mellitus Experimental/patologia , Gorduras na Dieta/efeitos adversos , Receptores Frizzled/fisiologia , Regulação da Expressão Gênica/fisiologia , Histonas/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/deficiência , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Camundongos , Camundongos Knockout , Miócitos de Músculo Liso/patologia , Osteopontina/biossíntese , Osteopontina/genética , Comunicação Parácrina , Mapeamento de Interação de Proteínas , Proteína-Arginina N-Metiltransferases/metabolismo , Receptores de Superfície Celular , Receptores de LDL/genética , Fatores Estimuladores Upstream/fisiologia , Rigidez Vascular/fisiologiaRESUMO
Background Postnatal catch-up growth and rapid weight gain after intrauterine growth restriction (IUGR) seem to increase the risk for later disease. This study aimed to compare features of the metabolic syndrome early in life between IUGR and appropriate for gestational age (AGA) infants. Patients Data for 9 infants with IUGR defined by a birth weight<10th percentile and ultrasound-proven placental insufficiency and 11 AGA children were available. Method Postnatal growth, auxological, cardiovascular, and metabolic parameters up to a chronological age of 6 years were assessed: Fasting serum concentrations of LDL-cholesterol, insulin, leptin, IGF-I, DHEAS, skinfold thicknesses, blood pressure, and mean carotid intima-media thickness (cIMT). Results All IUGR infants showed catch-up growth, although mean BMI SDS and total subcutaneous fat mass at the age of 6 years were still slightly lower compared to the AGA cohort. Reduced serum leptin concentrations were observed in IUGR infants (p=0.02), whereas no significant difference was found for IGF-I, insulin, LDL-cholesterol and DHEAS concentrations. Mean cIMT was significantly higher in IUGR infants (p<0.05). Mean arterial pressure did no differ. Discussion and Conclusion In 6-year-old IUGR infants with catch-up growth, who still had a slightly reduced BMI SDS compared to the AGA group, signs of subclinical atherosclerosis were detectable suggesting that cardiovascular risk in IUGR may be present even in the absence of excessive growth.
Assuntos
Arteriosclerose/etiologia , Estatura , Índice de Massa Corporal , Peso Corporal , Retardo do Crescimento Fetal/diagnóstico , Arteriosclerose/diagnóstico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etiologia , Gravidez , Fatores de RiscoRESUMO
Experimentally, regulatory T cells inhibit rejection. In clinical transplantations, however, it is not known whether T cell regulation is the cause for, or an epiphenomenon of, long-term allograft survival. Here, we study naïve and alloantigen-primed T cell responses of clinical lung transplant recipients in humanized mice. The pericardiophrenic artery procured from human lung grafts was implanted into the aorta of NODrag-/- /IL-2rγc-/- mice reconstituted with peripheral blood mononuclear cells (PBMCs) from the respective lung recipient. Naïve or primed allogeneic PBMCs procured 21 days post-lung transplantation with or without enriching for CD4+ CD25high T cells were used. Transplant arteriosclerosis was assessed 28 days later by histology. Mice reconstituted with alloantigen-primed PBMCs showed significantly more severe transplant arteriosclerosis than did mice with naïve PBMCs (p = 0.005). Transplant arteriosclerosis was equally suppressed by enriching for autologous naïve (p = 0.012) or alloantigen-primed regulatory T cells (Tregs) (p = 0.009). Alloantigen priming in clinical lung recipients can be adoptively transferred into a humanized mouse model. Transplant arteriosclerosis elicited by naïve or alloantigen-primed PBMCs can be similarly controlled by potent autologous Tregs. Cellular therapy with expanded autologous Tregs in lung transplantation might be a promising future strategy.
Assuntos
Arteriosclerose/etiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/imunologia , Isoantígenos/imunologia , Pneumopatias/imunologia , Transplante de Pulmão/efeitos adversos , Linfócitos T Reguladores/imunologia , Animais , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Pneumopatias/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Fenótipo , Transplantados , Transplante HomólogoRESUMO
SIOD is rare disorder related to SMARCAL1 or SMARCAL2 gene mutation, including (among other comorbidities) T-cell immunodeficiency, nephrotic syndrome, and renal failure. Up to 22% of primary patients may develop various autoimmune disorders. We report the case of 11-year-old male with SIOD, who presented ITP at 2 years after renal transplantation with decrease in platelet count (from normal) to 56 000/µL and then (gradually) to 2000/µL. There was no effect of iv. methylprednisolone/dexamethasone. As the presence of antibodies against GPIIb/IIIa, GPIb, and GPIaIIa platelet glycoproteins was confirmed, patient was given 50 g of IVIG and then was put on plasmapheresis; however, both showed poor direct effect. As we were afraid to give rituximab (due to expected overimmunosuppression), we prescribed the oral TPO-receptor agonist (eltrombopag). Patient responded after 17 days of therapy, to the final dose of 50 mg/d (approx. 2 mg/kg). The antiplatelet antibodies disappeared after four plasmapheresis. Overall, the therapy was continued for 7 weeks and was stopped at platelet count of 433 000/µL. Platelet count remained stable in 8-month follow-up. Combination of plasmapheresis and TPO-receptor agonist was effective in post-renal transplant acute ITP in patient with SIOD.
Assuntos
Arteriosclerose/tratamento farmacológico , Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Transplante de Rim/efeitos adversos , Síndrome Nefrótica/tratamento farmacológico , Osteocondrodisplasias/tratamento farmacológico , Embolia Pulmonar/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/cirurgia , Pirazóis/uso terapêutico , Arteriosclerose/etiologia , Criança , DNA Helicases/genética , Humanos , Síndromes de Imunodeficiência/etiologia , Masculino , Mutação , Síndrome Nefrótica/etiologia , Osteocondrodisplasias/etiologia , Plasmaferese , Contagem de Plaquetas , Doenças da Imunodeficiência Primária , Embolia Pulmonar/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Trombopoetina/metabolismo , Fatores de TempoRESUMO
Stiffness of the arterial wall and predicted vascular age as a predictor of cardiovascular disease when stress-induced hypertension in the military personnel. On the basis of the study of 156 men aged 30-55 years are considered diagnostic methods for stress-induced hypertension in the military personnel. Furthermore, using modern diagnostic methods determined stress effect on the development of stress-induced hypertension, and also the risk of cardiovascular diseases. In order to detect early signs of atherosclerosis used sphygmography, by means of which was determined by cardio ankle vascular index (CA VI), as well as the calculated vascular age. The study proposed a set of organizational, diagnostic and therapeutic measures to reduce the risk of cardiovascular diseases among military personnel exposed to occupational stressful load.
Assuntos
Índice Tornozelo-Braço , Arteriosclerose , Hipertensão , Estresse Psicológico , Túnica Média , Rigidez Vascular , Adulto , Arteriosclerose/etiologia , Arteriosclerose/patologia , Arteriosclerose/fisiopatologia , Humanos , Hipertensão/etiologia , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/complicações , Estresse Psicológico/patologia , Estresse Psicológico/fisiopatologia , Túnica Média/fisiologia , Túnica Média/fisiopatologiaRESUMO
Endothelial cells (ECs) apoptosis is an initial event in transplant arteriosclerosis (TA), resulting in allograft function loss. To elucidate the precise mechanisms of ECs apoptosis leading to neointimal smooth muscle cells (SMCs) accumulation during TA. We induced apoptosis in cultured ECs by overexpressing p53 through lentivirus-mediated transfection. ECs apoptosis induced the production of transforming growth factor (TGF)-ß1 in both apoptotic and neighboring viable cells, leading to increased TGF-ß1 in the culture media. Conditioned media from Ltv-p53-transfected ECs further promoted transition of cultured ECs to SM-like cells by activating TGF-ß/Smad3, PI3K/Akt/mTOR, and MAPK/ERK signaling in a TGF-ß-dependent manner. In transgenic rat aorta transplantation models, inhibition of ECs apoptosis in Bcl-xL(+/+) knock-in rat aortic allografts significantly reduced TGF-ß1 production both in allograft endothelia and in blood plasma, which in turn decreased accumulation of SM22α+ cells from transgenic recipient ECs originally marked with EGFP knock-in in neointima and alleviated TA. Systemic treatment with SIS3, AP23573, or PD98059 also prevented recipient ECs-originated SM-like cells accumulation and intima hyperplasia in aortic allografts. These data suggest that allograft EC apoptosis induced recipient endothelial-mesenchymal (smooth muscle) transition via TGF-ß signaling, resulting in recipient EC-derived SMC accumulation as a major mechanism of vascular remodeling during TA.
Assuntos
Aorta/transplante , Apoptose , Arteriosclerose/etiologia , Endotélio Vascular/patologia , Transição Epitelial-Mesenquimal , Músculo Liso Vascular/patologia , Fator de Crescimento Transformador beta/metabolismo , Aloenxertos , Animais , Arteriosclerose/metabolismo , Arteriosclerose/patologia , Western Blotting , Movimento Celular , Proliferação de Células , Células Cultivadas , Endotélio Vascular/metabolismo , Imunofluorescência , Técnicas Imunoenzimáticas , Masculino , Músculo Liso Vascular/metabolismo , Fosfatidilinositol 3-Quinases , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de SinaisRESUMO
BACKGROUND: Compared with bare-metal stents, neoatherosclerosis reportedly develops earlier and more frequently after drug-eluting stent (DES) implantation. This study evaluated the incidence, clinical presentation, and predictors of early neoatherosclerosis after DES implantation. METHODS: Neointimal characteristics were evaluated in 449 patients (482 lesions) who underwent follow-up optical coherence tomography ≤12 months after DES implantation (median 9.1 months) and displayed a mean neointimal thickness >100 µm. Neoatherosclerosis was defined as neointima with the presence of lipid or calcification. RESULTS: Early neoatherosclerosis, defined as occurrence of neoatherosclerosis within 12 months after DES implantation, was observed in 31 lesions (6.4%). Compared with patients without early neoatherosclerosis, those with early neoatherosclerosis presented with a higher incidence of clinical symptoms (13% vs 57%, respectively; P < .001) and had undergone a higher frequency of target-lesion revascularization (9% vs 55%, respectively; P < .001) at the time of optical coherence tomography follow-up. Multivariate logistic regression analysis showed that independent predictors of early neoatherosclerosis were hypertension (odds ratio 3.20, 95% CI 1.32-7.78, P = .010) and pre-stent low-density lipoprotein cholesterol ≥130 mg/dL at the time of the index procedure (odds ratio 3.89, 95% CI, 1.62-9.36, P = .002). CONCLUSIONS: Early neoatherosclerosis was detected in 6.4% of DES-treated lesions with neointimal thickness >100 µm at a median of 9.1 months after DES implantation. The occurrence of early neoatherosclerosis was significantly associated with presentation of clinical symptoms. Independent predictors of early neoatherosclerosis were hypertension and high pre-stent low-density lipoprotein cholesterol at the time of the index procedure.
Assuntos
Arteriosclerose/epidemiologia , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/patologia , Stents Farmacológicos/efeitos adversos , Neointima/patologia , Intervenção Coronária Percutânea/efeitos adversos , Arteriosclerose/diagnóstico , Arteriosclerose/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: Arteriosclerosis is a pathological, structural (media vascular calcification) and physiological (modified vascular smooth vessel cells; increased arterial stiffness) alteration of the vessel wall. Through improved assessment methods (functional and imaging), it has become a well-known phenomenon in recent decades. However, its clinical importance was underestimated until recently. MATERIALS AND METHODS: Currently available English-speaking data about conditions/diseases associated with arteriosclerosis, its clinical sequels, available diagnostic procedures and therapeutic modalities were reviewed and summarized. RESULTS: In recent decades, emerging data have brought about a better understanding of causes and consequences of arteriosclerosis and highlight its growing clinical impact. CONCLUSION: Although arteriosclerosis showed an independent clinical impact on cardiovascular morbidity and mortality, especially in patients with chronic kidney disease/end-stage renal disease (CKD/ESRD) and diabetes mellitus, convincing clinical therapy concepts are not available until now. The establishment of novel therapeutic strategies derived from basic research is strongly needed.
Assuntos
Envelhecimento , Arteriosclerose/diagnóstico , Calcificação Vascular/diagnóstico , Absorciometria de Fóton , Arteriosclerose/etiologia , Arteriosclerose/terapia , Conservadores da Densidade Óssea/uso terapêutico , Calcimiméticos/uso terapêutico , Calciofilaxia/complicações , Complicações do Diabetes , Diabetes Mellitus , Dietoterapia/métodos , Difosfonatos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imageamento por Ressonância Magnética , Fósforo na Dieta , Insuficiência Renal Crônica/complicações , Tomografia de Coerência Óptica , Tomografia Computadorizada por Raios X , Ultrassonografia de Intervenção , Calcificação Vascular/etiologia , Calcificação Vascular/terapiaRESUMO
BACKGROUND: The effects of advanced glycation end products (AGEs) on arteriosclerosis (AS) after kidney transplantation and the molecular mechanisms involved remain unclear. METHODS: Samples were collected from 30 healthy volunteers and 30 renal transplant recipients (RTRs) to determine the levels of AGEs and to observe both histological changes and α-smooth muscle actin (α-SMA) and osteopontin (OPN) expression. Furthermore, we analyzed α-SMA, OPN and integrin-linked kinase (ILK) in rat vascular smooth muscle cells (VSMCs) that were treated with AGEs and in ILK plasmid transfected rat VSMCs treated with AGEs. Finally, we measured the expression of ILK and the receptor for advanced glycation end (RAGE) products in rat VSMCs treated with AGEs and an anti-RAGE antibody. RESULTS: Significant differences in the histological changes, serum AGEs, and expression of α-SMA and OPN in arterial walls were noted between healthy volunteers and RTRs. Significant OPN and ILK overexpression and reduced α-SMA expression were detected in a time-dependent manner in rat VSMCs after treatment with AGEs. Similar outcomes were observed regarding the overexpression of ILK, and these results could be prevented via RAGE inhibition. CONCLUSIONS: AGEs may play a critical role in the formation and progression of AS after renal transplantation by inducing VSMCs-to-osteoblast trans-differentiation through the AGE/RAGE/ILK pathway.