OBJETIVO: analisar, por meio da morfometria digital, o espessamento intimal presente na artéria ilíaca de suínos, submetidos à angioplastia isoladamente e à angioplastia seguida do implante de stent. MATERIAIS E MÉTODOS: em dez suínos sadios, foi realizada a angioplastia de ambas as artérias ilíacas comuns (AIC) seguida do implante de um “Z” stent autoexpansível na AIC esquerda. Após quatro semanas, os animais foram sacrificados para a retirada de amostras de tecido arterial e preparo das lâminas histológicas de três grupos de peças de cada suíno divididas do seguinte modo: grupo 1, envolvendo o segmento arterial proximal do stent; grupo 2, envolvendo o segmento distal do stent; grupo 3, área da angioplastia da AIC direita. As imagens das lâminas foram digitalizadas e analisadas por programa de morfometria com cálculo da área luminal, área da camada íntima e área da camada média dos cortes histológicos. A análise estatística foi realizada através de média e desvio padrão das áreas em cada grupo, utilizando ANOVA, com teste Post-Hoc de Tukey e LSD. O valor de p≤0,05 foi considerado significativo. RESULTADOS: na análise das médias das áreas obtidas, foi encontrada uma diferença estatisticamente significativa quanto à camada íntima dos grupos 1 (5,41 mm²) e 2 (5,25 mm²), quando comparados ao grupo 3 (0,65 mm²), em relação à camada média dos grupos 1 (3,51 mm²) e 2 (3,70 mm²), quando comparados ao grupo 3 (5,59 mm²) e não se observou diferença significativa nas médias das áreas luminais dos três grupos (grupo 1: 6,63 mm²; grupo 2: 5,25 mm²; grupo 3: 5,78 mm²). CONCLUSÃO: a angioplastia da AIC do suíno, seguida do implante do stent, gerou um espessamento intimal maior do que aquele produzido apenas pela angioplastia; porém, a área da camada média apresentou-se diminuída nos grupos “angioplastia + stent”; a luz arterial não apresentou diferença entre estes grupos. / PURPOSE: to compare through digital morphometry, the intimal thickening of the ilíac arteries in pigs, submitted to isolated angioplasty and angioplasty followed by stent implantation. MATERIAL AND METHODS: the angioplasty was performed in 10 healthy pigs in both common ilac arteries (CIA), followed by a self-expanding stainless steel “Z” stent implantation in the left CIA. After four weeks, the animals where sacrificed and the aorto-iliac segment was dissected free of surrounding structures. Histologic slices where divided in three groups: left CIA in the area of the proximal implantation site of the stent (group 1), left CIA including the distal implantation site of the stent (group 2) and the region of angioplasty in the right CIA (group 3). The histological slices were digitalized to be analysed by morphometry with calculation of the luminal, intimal and media layers areas. Descriptive statistics analysis was performed through average and standard deviation of areas on each group, using ANOVA, with Tukey and LSD Post-Hoc tests. The value of p≤0.05 were considered significant. RESULTS: a significant statistic difference was observed when the median area of intimal layer of the groups 1 (5.41 mm²) and 2 (5.25 mm²) were compared with group 3 (0.65 mm²) and in the media layer area of the groups 1 (3.51 mm²) and 2 (3.70 mm²) when compared with group 3 (5.59 mm²). No difference was observed in luminal areas among the three groups (group 1: 6.63 mm²; group 2: 5.25 mm²; group 3: 5.78 mm²). CONCLUSION: angioplasty followed by stent insertion produces an intimal thickening bigger than that observed after simple angioplasty; however, the area of the media layer is smaller in the “angioplasty plus stent” groups; there is no significant change in the luminal area among the three groups.

OBJETIVO: analisar, por meio da morfometria digital, o espessamento intimal presente na artéria ilíaca de suínos, submetidos à angioplastia isoladamente e à angioplastia seguida do implante de stent. MATERIAIS E MÉTODOS: em dez suínos sadios, foi realizada a angioplastia de ambas as artérias ilíacas comuns (AIC) seguida do implante de um “Z” stent autoexpansível na AIC esquerda. Após quatro semanas, os animais foram sacrificados para a retirada de amostras de tecido arterial e preparo das lâminas histológicas de três grupos de peças de cada suíno divididas do seguinte modo: grupo 1, envolvendo o segmento arterial proximal do stent; grupo 2, envolvendo o segmento distal do stent; grupo 3, área da angioplastia da AIC direita. As imagens das lâminas foram digitalizadas e analisadas por programa de morfometria com cálculo da área luminal, área da camada íntima e área da camada média dos cortes histológicos. A análise estatística foi realizada através de média e desvio padrão das áreas em cada grupo, utilizando ANOVA, com teste Post-Hoc de Tukey e LSD. O valor de p≤0,05 foi considerado significativo. RESULTADOS: na análise das médias das áreas obtidas, foi encontrada uma diferença estatisticamente significativa quanto à camada íntima dos grupos 1 (5,41 mm²) e 2 (5,25 mm²), quando comparados ao grupo 3 (0,65 mm²), em relação à camada média dos grupos 1 (3,51 mm²) e 2 (3,70 mm²), quando comparados ao grupo 3 (5,59 mm²) e não se observou diferença significativa nas médias das áreas luminais dos três grupos (grupo 1: 6,63 mm²; grupo 2: 5,25 mm²; grupo 3: 5,78 mm²). CONCLUSÃO: a angioplastia da AIC do suíno, seguida do implante do stent, gerou um espessamento intimal maior do que aquele produzido apenas pela angioplastia; porém, a área da camada média apresentou-se diminuída nos grupos “angioplastia + stent”; a luz arterial não apresentou diferença entre estes grupos. / PURPOSE: to compare through digital morphometry, the intimal thickening of the ilíac arteries in pigs, submitted to isolated angioplasty and angioplasty followed by stent implantation. MATERIAL AND METHODS: the angioplasty was performed in 10 healthy pigs in both common ilac arteries (CIA), followed by a self-expanding stainless steel “Z” stent implantation in the left CIA. After four weeks, the animals where sacrificed and the aorto-iliac segment was dissected free of surrounding structures. Histologic slices where divided in three groups: left CIA in the area of the proximal implantation site of the stent (group 1), left CIA including the distal implantation site of the stent (group 2) and the region of angioplasty in the right CIA (group 3). The histological slices were digitalized to be analysed by morphometry with calculation of the luminal, intimal and media layers areas. Descriptive statistics analysis was performed through average and standard deviation of areas on each group, using ANOVA, with Tukey and LSD Post-Hoc tests. The value of p≤0.05 were considered significant. RESULTS: a significant statistic difference was observed when the median area of intimal layer of the groups 1 (5.41 mm²) and 2 (5.25 mm²) were compared with group 3 (0.65 mm²) and in the media layer area of the groups 1 (3.51 mm²) and 2 (3.70 mm²) when compared with group 3 (5.59 mm²). No difference was observed in luminal areas among the three groups (group 1: 6.63 mm²; group 2: 5.25 mm²; group 3: 5.78 mm²). CONCLUSION: angioplasty followed by stent insertion produces an intimal thickening bigger than that observed after simple angioplasty; however, the area of the media layer is smaller in the “angioplasty plus stent” groups; there is no significant change in the luminal area among the three groups.

OBJETIVO: analisar, por meio da morfometria digital, o espessamento intimal presente na artéria ilíaca de suínos, submetidos à angioplastia isoladamente e à angioplastia seguida do implante de stent. MATERIAIS E MÉTODOS: em dez suínos sadios, foi realizada a angioplastia de ambas as artérias ilíacas comuns (AIC) seguida do implante de um “Z” stent autoexpansível na AIC esquerda. Após quatro semanas, os animais foram sacrificados para a retirada de amostras de tecido arterial e preparo das lâminas histológicas de três grupos de peças de cada suíno divididas do seguinte modo: grupo 1, envolvendo o segmento arterial proximal do stent; grupo 2, envolvendo o segmento distal do stent; grupo 3, área da angioplastia da AIC direita. As imagens das lâminas foram digitalizadas e analisadas por programa de morfometria com cálculo da área luminal, área da camada íntima e área da camada média dos cortes histológicos. A análise estatística foi realizada através de média e desvio padrão das áreas em cada grupo, utilizando ANOVA, com teste Post-Hoc de Tukey e LSD. O valor de p≤0,05 foi considerado significativo. RESULTADOS: na análise das médias das áreas obtidas, foi encontrada uma diferença estatisticamente significativa quanto à camada íntima dos grupos 1 (5,41 mm²) e 2 (5,25 mm²), quando comparados ao grupo 3 (0,65 mm²), em relação à camada média dos grupos 1 (3,51 mm²) e 2 (3,70 mm²), quando comparados ao grupo 3 (5,59 mm²) e não se observou diferença significativa nas médias das áreas luminais dos três grupos (grupo 1: 6,63 mm²; grupo 2: 5,25 mm²; grupo 3: 5,78 mm²). CONCLUSÃO: a angioplastia da AIC do suíno, seguida do implante do stent, gerou um espessamento intimal maior do que aquele produzido apenas pela angioplastia; porém, a área da camada média apresentou-se diminuída nos grupos “angioplastia + stent”; a luz arterial não apresentou diferença entre estes grupos. / PURPOSE: to compare through digital morphometry, the intimal thickening of the ilíac arteries in pigs, submitted to isolated angioplasty and angioplasty followed by stent implantation. MATERIAL AND METHODS: the angioplasty was performed in 10 healthy pigs in both common ilac arteries (CIA), followed by a self-expanding stainless steel “Z” stent implantation in the left CIA. After four weeks, the animals where sacrificed and the aorto-iliac segment was dissected free of surrounding structures. Histologic slices where divided in three groups: left CIA in the area of the proximal implantation site of the stent (group 1), left CIA including the distal implantation site of the stent (group 2) and the region of angioplasty in the right CIA (group 3). The histological slices were digitalized to be analysed by morphometry with calculation of the luminal, intimal and media layers areas. Descriptive statistics analysis was performed through average and standard deviation of areas on each group, using ANOVA, with Tukey and LSD Post-Hoc tests. The value of p≤0.05 were considered significant. RESULTS: a significant statistic difference was observed when the median area of intimal layer of the groups 1 (5.41 mm²) and 2 (5.25 mm²) were compared with group 3 (0.65 mm²) and in the media layer area of the groups 1 (3.51 mm²) and 2 (3.70 mm²) when compared with group 3 (5.59 mm²). No difference was observed in luminal areas among the three groups (group 1: 6.63 mm²; group 2: 5.25 mm²; group 3: 5.78 mm²). CONCLUSION: angioplasty followed by stent insertion produces an intimal thickening bigger than that observed after simple angioplasty; however, the area of the media layer is smaller in the “angioplasty plus stent” groups; there is no significant change in the luminal area among the three groups.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O presente estudo avaliou a possÃvel proteÃÃo do tenoxicam ( txc ), um antiinflamatÃrio nÃo esterÃide, em um modelo experimental de isquemia-reperfusÃo. Foram utilizados ratos machos com idade acima de 1 ano Wistar (200-450g), submetidos à oclusÃo das artÃrias carÃtidas comuns por 45 min e decapitados 1h ou 24 h apÃs a isquemia, para a retirada do cÃrebro e dissecÃÃo dos hipocampos . Os animais foram divididos em 5 grupos : 1) Isquemia ; 2) Isquemia + txc 2,5mg/Kg IP; 3) Isquemia + txc 10mg/Kg IP ; 4) Controle falso-operado e 5) controle + txc 10 mg/kg I.P. A anÃlise histolÃgica revelou alteraÃÃo significativa no grupo 1 em relaÃÃo ao 4 usando-se uma escala de escores variando de 0 a 3. O uso do txc revela uma tendÃncia para reversÃo das lesÃes. A atividade da enzima mieloperoxidase mostrou aumento significativo no grupo 1 em relaÃÃo ao 4 revertidos para valores de controle com o uso de dose Ãnica de txc (2,5 ou 10 mg/kg, i.p.). Os nÃveis de nitrito tambÃm aumentaram no grupo 1 e com o uso do txc houve tendÃncia para atenuaÃÃo desses valores. Houve aumento nos nÃveis de dopamina no grupo 1 que foi revertido com o uso do txc em ambas as doses . Os nÃveis de glutamato se elevaram no grupo 1 mesmo apÃs 24 h de reperfusÃo que sugere um maior dano da excitotoxicidade nos animais idosos. Os nÃveis de ATP na reperfusÃo por 1 h foram inferiores em relaÃÃo aos de 24 h, refletindo ainda lesÃo mesmo no inÃcio da reperfusÃo. Os nÃveis de lactato aumentaram nos grupos 3 e 5 reperfundidos por 24 h em relaÃÃo aos de 1 h , sugerindo maior dano metabÃlico nos animais idosos. Os nÃveis de piruvato diminuÃram na reperfusÃo por 24 h em relaÃÃo aos de 1 h, refletindo uma normalizaÃÃo da atividade da enzima piruvato-desidrogenase, restabelecendo a taxa metabÃlica desse substrato. O possÃvel papel neuroprotetor do txc na reversÃo dos danos secundÃrios à reperfusÃo na lesÃo isquÃmica à associado à sua aÃÃo anti-inflamatÃria, inibindo a atividade da COX e reduzindo a cascata inflamatÃria desencadeada no processo isquÃmico, com reduÃÃo da infiltraÃÃo de cÃlulas inflamatÃrias, inibiÃÃo indireta da produÃÃo de citocinas e quimocinas e reduÃÃo da produÃÃo de radicais livres e lesÃo neuronal. O txc pode ser portanto uma possÃvel alternativa no tratamento de doenÃas vasculares cerebrais isquÃmicas, como uma terapia adjuvante por exemplo ao uso de trombolÃticos / The present work shows effects of tenoxicam (TXC ) in rats submitted to transient cerebral ischemia. Male aged Wistar rats (250-450g) were submitted to the both common carotid arteries occlusion with aneurysmal clips to induce ischemia. At the end of 45 min of bilateral carotid arteries occlusion (BCAO), blood flow was restored by releasing the clips and the incision was closed with a single suture. After 1h or 24h of reperfusion, the rats were decapitated, brains dissected and hippocampi removed for measurements of MPO activity, nitrite , monoamine , glutamate/aspartate, ATP, lactate and piruvate levels. The animals were divided in 5 groups (N=4-10): 1) sham-operated, 2) BCAO, 3) BCAO + TXC 2.5mg/kg, 4) BCAO + TXC10mg/kg and 5) sham-operated + TXC 10mg/kg . The TXC administration was made after 45 minutes of BCAO. The histological analysis were made and showed significant changes on group 2 in comparison with group 1 (p<0.05, Kruskal-Wallis and Dunnâ test). The use of TXC showed a tendency of decrease these alterations. The MPO activity in the group 2 was significantly greater than that in the group 1 (p< 0.0001, ANOVA and Tukey). The treatment with TXC reduced the MPO activity to control levels (p<0.0001, ANOVA and Tukey). There was increased levels of nitrite in the group 2 in comparison with group 1 (p<0.05), and the treatment with TXC failed to attenuate the ischemic levels. The hippocampal levels of DA were increased after ischemia when compared with group 1 (p<0.01, Anova e Dunnett ) and were reverted with TXC in both doses (p<0.01, Anova e Dunnett). Hippocampal level from group 2 of both glutamate and aspartate were higher than group 1 (p < 0.05 , ANOVA , Dunnettâs Test). Ischemia-induced elevations in glutamate and aspartate were not attenuated with TXC . The ATP levels have showed decreases in the group with 1 h of reperfusion in comparison with 24 h . The lactate levels were increased in the 24 h reperfusionâs group in relation of 1 h. These results indicated more metabolic damage in aged rats. So, the neuroprotective role of TXC is possibly through the anti-inflammatory action with inhibition of cyclooxygenase activity, and interfering on the inflammatory process of post-ischemic reperfusion. The TXC, therefore, could be a possible therapeutic alternative on stroke treatment like an adjunct drug associated with, for example, a thrombolitic

No description available.

The educational medium GetWellNetWork (GWNW) in a large magnet teaching facility offered few educational videos specific to vascular patients with a focus on leg elevation after lower extremity bypass surgery. Supplying patient-specific education has the potential for providing cost-effective nursing care to vascular patients and improving hospital reimbursement. Guided by the interactive care model, a storyboard was developed using best-practice evidence for vascular postoperative patients that could lead to the development of a video to address the educational needs of vascular patients upon discharge. The practice focused question asked if a video addressing the importance of leg elevation would improve patients’ use of in-house educational videos and stakeholder satisfaction. A vascular physician (n = 1) and nursing staff (n = 9) provided feedback on the appropriateness of the evidence-based educational content for the storyboard by completing a 9-item, open-ended survey. Survey results supported development of the video and revealed positive feedback on storyboard content and that staff with 1–3 years’ experience or 15+ years’ experience had an increased understanding of the importance of evidence-based guidelines for leg elevation for vascular patients. The feedback will be used to develop a vascular-patient-specific educational video. Encouraging patients to view the video on leg elevation has the potential to improve cost effectiveness of patient care and hospital reimbursement, prevent hospital readmission that could lead to patient and caregiver hardships associated with readmission, and improve the health outcomes for postoperative vascular patients.

Sirtuin-1 (SirT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacetylase expressed ubiquitously in the body. In the vasculature, SirT1 is present in endothelial and vascular smooth muscle cells (VSMCs), where it has been shown to promote anti-inflammatory and anti-oxidant effects. As a result, SirT1 is known to play a protective role in the vasculature wall from pathologies such as atherosclerosis, arterial stiffness, and aortic aneurysm. Hence, SirT1 is considered an attractive therapeutic target for vascular diseases and potentially, aging-related and metabolic diseases. However, currently available SirT1 activators have failed to reach the clinic. Thus, novel approaches to activate SirT1 are needed. In this study, we first sought to optimize a novel fluorescence-based SirT1 activity assay, with which to reliably assess intracellular SirT1 activity and the efficacy of SirT1 activators and inhibitors. We next sought to use the SirT1 activity assay to screen novel compounds identified by an in silico docking analysis and hypothesized to activate SirT1. Lastly, we generated adeno-associated viruses (AAV) overexpressing wildtype (WT) or a redox-resistant (3M) SirT1 to analyze the effects of overexpressing SirT1 in VSMCs, in normal and oxidative stress conditions. For the activity assay, our results showed that an optimal standard curve range was between 0 ng and 12 ng of substrate (acetylated-p53 peptide). After testing different commercially available human recombinant SirT1s, the Anaspec SirT1 of the highest concentration showed a decrease in measured fluorescence for acetylated-p53 peptide with higher SirT1 (ng), indicating the enzyme and the assay were functional. However, when novel small molecules (A4, B4, and G3) hypothesized to activate SirT1 were added to reactions, the total p53 peptide fluorescence values increased compared to the control, suggesting some interference of the molecules with the assay detection. After AAV infection in VSMCs, SirT1 expression, measured by HA-tag, increased for AAV WT (n=3, p=0.04) and similarly for AAV 3M SirT1, indicating that the AAVs efficiently infect VSMCs. SirT1 activity, measured by Western Blot as decreased acetylated-histone (H3), also appeared to increase for both AAV WT and AAV 3M. A similar trend was shown for VSMCs under oxidant stress conditions (n=2). In conclusion, we successfully established a standard curve range for a novel SirT1 activity assay. Further trials are needed to ensure activity assay reproducibility before testing the efficacy of SirT1 activators and inhibitors. Infection of AAV WT and 3M SirT1 led to an increase in the expression and activity of SirT1 in VSMCs. The expression of SirT1 by AAV may be a promising therapeutic option for in vivo prevention and treatment of vascular diseases. / 2026-03-01T00:00:00Z

No / T-type Ca2+ channels regulate proliferation in a number of tissue types, including vascular smooth muscle and various cancers. In such tissues, up-regulation of the inducible enzyme heme oxygenase-1 (HO-1) is often observed, and hypoxia is a key factor in its induction. HO-1 degrades heme to generate carbon monoxide (CO) along with Fe2+ and biliverdin. Since CO is increasingly recognized as a regulator of ion channels (Peers et al. 2015), we have explored the possibility that it may regulate proliferation via modulation of T-type Ca2+ channels. Whole-cell patch-clamp recordings revealed that CO (applied as the dissolved gas or via CORM donors) inhibited all 3 isoforms of T-type Ca2+ channels (Cav3.1-3.3) when expressed in HEK293 cells with similar IC50 values, and induction of HO-1 expression also suppressed T-type currents (Boycott et al. 2013). CO/HO-1 induction also suppressed the elevated basal [Ca2+ ]i in cells expressing these channels and reduced their proliferative rate to levels seen in non-transfected control cells (Duckles et al. 2015). Proliferation of vascular smooth muscle cells (both A7r5 and human saphenous vein cells) was also suppressed either by T-type Ca2+ channel inhibitors (mibefradil and NNC 55-0396), HO-1 induction or application of CO. Effects of these blockers and CO were non additive. Although L-type Ca2+ channels were also sensitive to CO (Scragg et al. 2008), they did not influence proliferation. Our data suggest that HO-1 acts to control proliferation via CO modulation of T-type Ca2+ channels.

Para avaliar o efeito de uma refeição-teste rica em lipídeos, assim mimetizando o estado pós-prandial durante o dia, nos parâmetros metabólicos e na reatividade vascular, foram estudados quatro grupos de pacientes do sexo masculino, assim divididos: com diabetes mellitus Tipo 2 e sem doença arterial coronariana (DM, n = 10), com doença arterial coronariana e com diabetes mellitus Tipo 2 (DM + DAC, n = 11), com doença arterial coronariana e sem diabetes mellitus (DAC, n = 11) e Controle (n = 7). Todos os pacientes, após receberem uma dieta rica em gordura (60g) e pobre em hidratos de carbono (14g), foram avaliados em termos de perfil lipídico antes (0h) e 2h, 4h, 6h e 8h após a ingestão e realizada a avaliação da reatividade vascular nos tempos 0h, 4h e 8h. A reatividade vascular foi estudada por ultra-som de alta resolução, medindo-se a resposta vasodilatadora da artéria braquial durante hiperemia reativa (vasodilatação endotélio-dependente) e após administração de nitroglicerina (endotélio-independente). HbA1c não foi diferente entre os grupos do estudo, exceto, como seria de se esperar, nos Controles, que foi normal (média ± DP) (DAC: 6,3 ± 0,6% vs DM + DAC: 7,6 ± 1,6% vs DM: 6,8 ± 1,7% vs Controle: 5,43 ± 0,45%). Por outro lado, a glicemia e insulina de jejum foram significativamente menores dos DAC e grupo Controle, sendo similar nos dois grupos. Dos outros parâmetros metabólicos, apenas o ácido úrico foi significativamente maior no grupo DAC (p = 0,025) em comparação aos outros. Vasodilatação da artéria braquial pós-isquemia antes do teste de sobrecarga foi semelhante entre os grupos (DAC: 7,44 ± 4,30% vs 7,01 ± 4,53% no DM vs 10,34 ± 5,10% no DM+DAC vs 9,91 ± 2,97% no grupo Controle. A vasodilatação após administração de nitrato (realizada no dia anterior ao teste de sobrecarga lipídica) também se manteve dentro da normalidade nos quatro grupos, sem diferença entre eles (DAC: 19,85 ± 8,66% vs 15,68 ± 11,43% no DM vs 21,24 ± 11,82% no DM+DAC e 20,05 ± 3,73% no grupo Controle). HOMAIR (Homeostasis Model for Assessment of insulin resistance) aumentou progressivamente nos grupos DAC, DM e DM+DAC, respectivamente, sendo significativamente menor no grupo Controle. Após sobrecarga, os níveis de triglicerídeos aumentaram significativamente nos quatro grupos, com pico nos tempos 4h e 6h (p < 0,001 nos quatro grupos para 2h, 4h, 6h e 8h vs 0h). O colesterol total apresentou aumento, com p < 0,001 para 4h e 6h e p = 0,0019 para 8h, em comparação com 0h, nos quatro grupos. O LDL-colesterol (p = 0,001) e o HDL-colesterol (p < 0,001) apresentaram decréscimo em todos os tempos após o teste em relação ao basal. Não houve diferença significativa entre os quatro grupos no perfil lipídico após sobrecarga de gordura. A glicemia foi significativamente mais baixa nos grupos DAC e Controle do que nos grupos DM e DM+DAC. Nos grupos DAC e Controle, a glicemia manteve-se inalterada durante o teste. Os grupos DM e DM+DAC apresentaram um decréscimo significativo nos níveis glicêmicos nos tempos 4h, 6h e 8h. (p<0,001 para todos os grupos em relação ao tempo 0h). O comportamento da insulinemia foi semelhante entre os grupos e todos mostraram elevação nos tempos 2h (p<0,001) vs 0h, havendo progressiva queda no decorrer dos tempos, chegando aos níveis basais na oitava hora. A reatividade vascular foi semelhante entre os quatro grupos e não houve diferença nas medidas após sobrecarga. No grupo DM ocorreu uma redução limítrofe na reatividade vascular após a ingestão da sobrecarga lipídica (p = 0,0556). A vasodilatação pós-nitroglicerina também foi semelhante entre os grupos, assim como os resultados obtidos antes e após sobrecarga quando comparados entre si. Este estudo permitiu concluir que a hiperlipemia pós-sobrecarga lipídica nos grupos DAC, DM, DM+DAC e Controle resultou em hiperinsulinemia sem elevação glicêmica, mas sem efeito significativo da reatividade vascular, tanto quando avaliada pela hiperemia reativa (endotélio-dependente), quanto quando estimulada com vasodilatador (endotélio-independente) / To assess the effect of a high-fat meal to simulate to post-prandial state during the day, on the metabolic parameters and endothelial function, four groups of male patients with Coronary Heart Disease and without Diabetes Mellitus (DAC, n= 11); with known Type 2 Diabetes Mellitus and no Coronary Heart Disease (DM, n= 10); and with both Type 2 Diabetes and Coronary Heart Disease (DM+DAC, n = 11) as well as seven healthy controls (Control n = 7) were evaluated before and after receiving a high fat (60g) low carbohydrate (14g) meal test. Lipid profile (basal and 2, 4, 6 and 8 hours after the meal-test) and Vascular reactivity (2, 4 and 8h) were measured. Vascular reactivity was evaluated using high-resolution ultrasound and assessing brachial artery\'s vasodilatory responses during reactive hyperemia (endothelium-dependent vasodilatation), and after nitroglycerin administration, an endotheliumindependent vasodilator. Mean ± SD HbA1c was not significantly by different between groups (DAC: 6.3 ± 0.6% vs DM + DAC: 7.6 ± 1.6% vs DM: 6.8 ± 1,7%) except, as expected in the Control (5.43 ± 0.45%). Furthermore, fasting plasma glucose and insulin were significantly lower in the DAC and Control being however similar in both groups. DAC group had significant by higher uric acid levels than the other three groups (p = 0.025). Post-ischemia brachial artery vasodilation was similar among groups before lipid overload (DAC: 7.44 ± 4.30% vs 7.01 ± 4.53% no DM vs 10.34 ± 5.10% no DM+DAC vs 9.91 ± 2.97% in the Control). Basal change in the brachial artery diameter after sublingual nitrate, performed the day before the fat test, was also within the accepted normal range in all four groups, with no difference in between them (DAC: 19.85 ± 8.66% vs 15.68 ± 11.43 in DM vs 21.24 ± 11.82% in DM+DAC and 20.05 ± 3.73% in the Control). Homeostasis Model for Assessment of insulin sensitivity (HOMAIR) increased significantly and progressively from DAC to DM and to DM+DAC groups, however being significantly lower in the Control. After the fat overload test all four groups had a major increase in triglyceride levels peaking at 4h and 6h after the ingestion (p<0.001) for four groups for 2h, 4h, 6h and 8h vs 0h). Total cholesterol had a increase at all times of sampling (p < 0.001), while LDL-cholesterol (p < 0.001) and HDL-cholesterol (p = 0.001) decreased after the test-meal. Overall, there were no statistical differences among the four groups regarding post load-lipid profile. Glycemia was statistically lower in DAC and Control versus DM and DM+DAC groups. In DAC and Control glicemia was unchanged during testing, DM and DM+DAC groups had a considerable glycemic decrease at times 4h, 6h and 8h after fat-load (p<0.001, for both groups vs 0h). Insulin behaviors was similar among all four groups all of which showed higher levels at 2h (p<0.001 vs 0h, there being a progressive decrease during the test becoming within the basal range at the 8th hour. Vascular reactivity was similar within the four groups and there was no difference through the different measures after fat-loading. In the diabetic group without coronary hearth disease there was a borderline reduction in vascular reactivity after the fat load (p = 0.0556). Vasodilation after nitroglycerin was comparable among the groups again with no differences in the response before and after fat-loading. In conclusion this study showed than the post-load hyperlipemia in DAC,DM, DM+DAC and Control groups resulted in hyperinsulinemia without hyperglycemia and had no significant effects on vascular reactivity both endothelial dependent (hyperemia reactivity) and independent

Tumor-like proliferative vascular lesions manifest in several diseases such as peripheral arterial disease (PAD) and atherosclerosis (AS) after arterial injury. The cause of the vascular cell dysfunction in PAD patients is not known. Our recent novel discovery shows that inhibitor of differentiation 3 (ID3) is highly expressed in intimal lesions of clinical vascular disease samples. The central hypothesis of our study is: estrogenic chemical induced dysregulation of ID3 target genes is involved in the development of vascular disease. NHANES data analysis demonstrated higher geometric levels of all 6 PCB congeners in both PAD diagnosed participants and participants at risk of AS when compared to the rest of the population. Adjusted models showed association between higher exposure of PCBs, phthalates, BPA, and increased risk of PAD. Furthermore PCB153 was shown to have the highest geometric mean amongst all PCB congeners in both participants diagnosed with PAD and at risk of AS. Gene expression of ID3 & ID3 candidate targets in blood & tissue studies identified ID3 & ID3 candidate target genes as a driver of vascular disease. Overlapping ID3 & ID3 candidate target genes included: ABCB6, ACP1, BYSL, CAD, CDH15, DCBLD2, DHRS3, DNMT1, ID3, MCM4, and NDUFA7. The ID3 target genes involved in the: focal adhesion pathway were ACTN1, COL1A2, COL3A1, COL6A1, CTNNB1, IBSP, ID3, ITGA8, and MYL2; ECM-receptor interaction were COL1A2, COL3A1, COL6A1, IBSP, ID3, and ITGA8; oxidative phosphorylation pathway ATP5D, ATP5H, ATP6V0B, ATP6V0D1, ATP6V1B2, COX5A, COX7C, COX8A, CYC1, ID3, NDUFA1, NDUFA7, NDUFS4, NDUFV1, NDUFV2; and cell cycle pathway ANAPC10, ATM, CDKN2B, E2F5, MCM3, and MCM4. In summary our results showed an association between exposure to PCBs, phthalates, BPA, and increased risk of PAD and AS, and possible molecular mechanisms of interaction of ID3 target genes and estrogenic chemicals involved in PAD and AS.