RESUMO
Calcification is common in atherosclerotic plaque and can induce vulnerability, which further leads to myocardial infarction, plaque rupture and stroke. The mechanisms of atherosclerotic calcification are poorly characterized. Interleukin enhancer binding factor 3 (ILF3) has been identified as a novel factor affecting dyslipidemia and stroke subtypes. However, the precise role of ILF3 in atherosclerotic calcification remains unclear. In this study, we used smooth muscle-conditional ILF3 knockout (ILF3SM-KO) and transgenic mice (ILF3SM-Tg) and macrophage-conditional ILF3 knockout (ILF3M-KO) and transgenic (ILF3M-Tg) mice respectively. Here we showed that ILF3 expression is increased in calcified human aortic vascular smooth muscle cells (HAVSMCs) and calcified atherosclerotic plaque in humans and mice. We then found that hyperlipidemia increases ILF3 expression and exacerbates calcification of VSMCs and macrophages by regulating bone morphogenetic protein 2 (BMP2) and signal transducer and activator of transcription 1 (STAT1) transcription. We further explored the molecular mechanisms of ILF3 in atherosclerotic calcification and revealed that ILF3 acts on the promoter regions of BMP2 and STAT1 and mediates BMP2 upregulation and STAT1 downregulation, which promotes atherosclerotic calcification. Our results demonstrate the effect of ILF3 in atherosclerotic calcification. Inhibition of ILF3 may be a useful therapy for preventing and even reversing atherosclerotic calcification.
Assuntos
Arteriolosclerose/etiologia , Proteína Morfogenética Óssea 2/genética , Hiperlipidemias/fisiopatologia , Proteínas do Fator Nuclear 90/metabolismo , Fator de Transcrição STAT1/genética , Animais , Peso Corporal , Proteína Morfogenética Óssea 2/metabolismo , Regulação da Expressão Gênica , Humanos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Proteínas do Fator Nuclear 90/genética , Regiões Promotoras Genéticas , Fator de Transcrição STAT1/metabolismo , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Calcificação Vascular/fisiopatologiaRESUMO
Studying the neuropathologic autopsy findings in subjects with chronic kidney disease (CKD) or chronic renal failure (CRF) is difficult for several reasons: etiology of the CKD may be heterogeneous, affected patients may have one or more major co-morbidities that themselves can cause significant neurologic disease, and agonal events may result in significant findings that were of minimal significance earlier in a patient's life. We studied the constellation of neuropathologic abnormalities in 40 autopsy brains originating from subjects of ages 34-95 years (no children in the study). The most common pathologic change was that of ischemic infarcts (cystic, lacunar and/or microinfarcts), which were seen in over half of subjects. These were associated with both large artery atherosclerosis and arteriolosclerosis (A/S), the latter finding being present in 29/40 subjects. Charcot-Bouchard microaneurysms were present in the brains of three subjects, in one case associated with severe amyloid angiopathy. Microvascular calcinosis (medial sclerosis in the case of arterioles) was seen in the basal ganglia (n=8) and/or endplate region of the hippocampus (n=7) and occasional ischemic infarcts in one brain showed severe calcification. Sequelae of cerebrovascular disease (especially A/S or microvascular disease) are a common neuropathologic substrate for neurologic disability and brain lesions in this complex group of patients. Regulation of calcium metabolism within brain microvessel walls may be worthy of further research in both human brain specimens and animal models.
Assuntos
Encéfalo/irrigação sanguínea , Artérias Cerebrais/patologia , Transtornos Cerebrovasculares/patologia , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Arteriolosclerose/etiologia , Arteriolosclerose/patologia , Autopsia , Doenças de Pequenos Vasos Cerebrais/etiologia , Doenças de Pequenos Vasos Cerebrais/patologia , Transtornos Cerebrovasculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Calcificação Vascular/etiologia , Calcificação Vascular/patologiaRESUMO
BACKGROUND: Hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA) may contribute to the development of mixed cerebral microbleeds (CMBs). Recently, the total small vessel disease (SVD) scores for HA and CAA were proposed, which are determined by a combination of MRI markers to reflect overall severity of these microangiopathies. OBJECTIVE: We investigated whether or not total HA-SVD and CAA-SVD scores could be used to predict overlap of HA and CAA in patients with mixed CMBs. METHODS: Fifty-three subjects with mixed CMBs were retrospectively analyzed. MRI markers (CMBs, lacunes, perivascular space, white matter hyperintensity [WMH] and cortical superficial siderosis [cSS]) were assessed. The HA-SVD score and CAA-SVD score were obtained for each subject. Anterior or posterior WMH was also assessed using the age-related white matter changes scale. RESULTS: The two scores were positively correlated (ρ=â0.449, pâ<â0.001). The prevalence of lobar dominant CMB distribution (pâ<â0.001) and lacunes in the centrum semiovale (pâ<â0.001) and the severity of WMH in the parieto-occipital lobes (pâ=â0.004) were significantly higher in the high CAA-SVD score group. cSS was found in four patients with high CAA-SVD score who showed lobar-dominant CMB distribution and severe posterior WMH. CONCLUSION: Mixed CMBs are mainly due to HA. Assessing both two scores may predict the overlap of HA and CAA in individuals with mixed CMBs. Patients with a high CAA-SVD score may have some degree of advanced CAA, especially when lobar predominant CMBs, severe posterior WMH, lobar lacunes, or cSS are observed.
Assuntos
Arteriolosclerose/diagnóstico por imagem , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Arteriolosclerose/etiologia , Angiopatia Amiloide Cerebral/complicações , Hemorragia Cerebral/etiologia , Doenças de Pequenos Vasos Cerebrais/etiologia , Feminino , Humanos , Hipertensão/complicações , Leucoencefalopatias/diagnóstico por imagem , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: Overweight has been related to renal arteriolosclerosis and is able to modify intrarenal haemodynamics. Increasing evidence suggests an association between weight in excess and primary glomerulonephritis (GN). The aim of this study was to evaluate the relationship between nutritional status and intrarenal arterial stiffness in primary GN associated to arteriolosclerosis. We have considered the glomerular diameter (GD) as morphological parameter in overweight and obese patients. METHODS: Clinical, laboratory, anthropometric data and renal Doppler ultrasound were performed immediately before kidney biopsy. RESULTS: Primary GN was diagnosed in 92 patients. Mild arteriolosclerosis was found in 19.6% of patients, moderate in the 20.6%, severe in the 10.9% while nephroangiosclerosis was diagnosed in 8.7% of patients. A positive correlation was found between body mass index (BMI) and renal resistive index (RRI) (P < 0.01, r = 0.34). RRI were significantly higher in patients with severe arteriolosclerosis at kidney biopsy (P < 0.05). Furthermore, higher BMI (P < 0.01) was found in patients with renal arteriolosclerosis than patients without renal arteriolosclerosis (26.1 ± 4.4 kg/m2 vs. 24.4 ± 4.5 kg/m2 ). Finally, in overweight and obesity patients we found a positive correlation between maximal GD and BMI (P < 0.01) and maximal GD and RRI (P < 0.01). CONCLUSION: In overweight and obese patients affected by primary GN, it might be found not only glomerular but also renal vascular lesions. Finally, we believe that nephroangiosclerosis, in combination with weight in excess, is able to modify intrarenal haemodynamic parameters. Moreover, in response to these changes, the renal tissue morphologically promotes a GD increase regardless of the underlying GN.
Assuntos
Arteriolosclerose/etiologia , Índice de Massa Corporal , Glomerulonefrite/etiologia , Adulto , Idoso , Feminino , Hemodinâmica , Humanos , Rim/patologia , Rim/fisiopatologia , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicaçõesRESUMO
People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aß) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, atherosclerosis and arteriolosclerosis were used as measures of cerebrovascular pathology and compared in post mortem tissue from individuals with DS (n = 32), sporadic AD (n = 80) and controls (n = 37). CAA was observed with significantly higher frequencies in brains of individuals with DS compared to sporadic AD and controls. Atherosclerosis and arteriolosclerosis were rare in the cases with DS. CAA in DS may be a target for future interventional clinical trials.
Assuntos
Doença de Alzheimer/complicações , Arteriolosclerose/etiologia , Aterosclerose/etiologia , Angiopatia Amiloide Cerebral/etiologia , Síndrome de Down/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Arteriolosclerose/patologia , Aterosclerose/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , ProbabilidadeRESUMO
Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative data sets. Previous studies showed evidence of distinct neurodegenerative disease outcomes and clinical-pathological correlations in the "oldest-old" compared to younger cohorts. Therefore, using the National Alzheimer's Coordinating Center data set, we analyzed clinical and neuropathological data from two groups according to ages at death: < 80 years (n = 1008) and ≥80 years (n = 1382). In both age groups, severe brain arteriolosclerosis was associated with worse performances on global cognition tests. Hypertension (but not diabetes) was a brain arteriolosclerosis risk factor in the younger group. In the ≥ 80 years age at death group, an ABCC9 gene variant (rs704180), previously associated with aging-related hippocampal sclerosis, was also associated with brain arteriolosclerosis. A post-hoc arterial spin labeling neuroimaging experiment indicated that ABCC9 genotype is associated with cerebral blood flow impairment; in a convenience sample from Alzheimer's Disease Neuroimaging Initiative (n = 15, homozygous individuals), non-risk genotype carriers showed higher global cerebral blood flow compared to risk genotype carriers. We conclude that brain arteriolosclerosis is associated with altered cognitive status and a novel vascular genetic risk factor.
Assuntos
Envelhecimento/psicologia , Arteriolosclerose/etiologia , Arteriolosclerose/psicologia , Cognição , Idoso , Idoso de 80 Anos ou mais , Arteriolosclerose/genética , Encéfalo/patologia , Encéfalo/fisiopatologia , Circulação Cerebrovascular/genética , Bases de Dados Factuais , Variação Genética , Humanos , Hipertensão/complicações , Fatores de Risco , Receptores de Sulfonilureias/genéticaRESUMO
Because calcineurin inhibitor (CNI) immunosuppressive drugs induce arteriolar hyalinosis (ah) in kidney transplants, ah lesions can potentially provide information about drug exposure. We studied the relationship of ah lesions to findings and outcomes in 562 indication biopsies taken 3 days to 35 years after transplant. Prevalence of ah lesions increased with time of biopsy after transplant (TxBx). The ah scores correlated with arterial intimal thickening and atrophy-fibrosis but, unlike atrophy-fibrosis, did not increase until after 500 days because of a background of ah1 lesions in early biopsies reflecting donor aging. Correlation of ah scores with other features varied with TxBx-in early biopsies, donor age and related changes, and in very late biopsies, chronic antibody-mediated rejection and glomerulonephritis and associated lesions. After correction for TxBx, ah0 in intermediate time periods was associated with increased risk of T cell-mediated rejection and graft loss, probably because of underimmunosuppression and nonadherence. Thus, ah lesions in indication biopsies have multiple associations: donor age (early, usually ah1), chronic glomerular diseases (late, often ah2/3), and adequate exposure to CNIs at intermediate times. This threefold TxBx-dependent complexity must be considered when interpreting indication biopsies: ah lesions often indicate adequate CNI exposure, not toxicity, and unexpected ah0 should increase vigilance for nonadherence and underimmunosuppression.
Assuntos
Arteriolosclerose/patologia , Rejeição de Enxerto/patologia , Hialina/metabolismo , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteriolosclerose/etiologia , Arteriolosclerose/metabolismo , Criança , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/metabolismo , Sobrevivência de Enxerto , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
Hyperphosphorylated transactive response DNA-binding protein 43 (TDP-43, encoded by TARDBP ) proteinopathy has recently been described in ageing and in association with cognitive impairment, especially in the context of Alzheimer's disease pathology. To explore the role of mixed Alzheimer's disease and TDP-43 pathologies in clinical Alzheimer's-type dementia, we performed a comprehensive investigation of TDP-43, mixed pathologies, and clinical Alzheimer's-type dementia in a large cohort of community-dwelling older subjects. We tested the hypotheses that TDP-43 with Alzheimer's disease pathology is a common mixed pathology; is related to increased likelihood of expressing clinical Alzheimer's-type dementia; and that TDP-43 pathologic stage is an important determinant of clinical Alzheimer's-type dementia. Data came from 946 older adults with ( n = 398) and without dementia ( n = 548) from the Rush Memory and Aging Project and Religious Orders Study. TDP-43 proteinopathy (cytoplasmic inclusions) was present in 496 (52%) subjects, and the pattern of deposition was classified as stage 0 (none; 48%), stage 1 (amygdala; 18%), stage 2 (extension to hippocampus/entorhinal; 21%), or stage 3 (extension to neocortex; 14%). TDP-43 pathology combined with a pathologic diagnosis of Alzheimer's disease was a common mixed pathology (37% of all participants), and the proportion of subjects with clinical Alzheimer's-type dementia formerly labelled 'pure pathologic diagnosis of Alzheimer's disease' was halved when TDP-43 was considered. In logistic regression models adjusted for age, sex, and education, TDP-43 pathology was associated with clinical Alzheimer's-type dementia (odds ratio = 1.51, 95% confidence interval = 1.11, 2.05) independent of pathological Alzheimer's disease (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis). Mixed Alzheimer's disease and TDP-43 pathologies were associated with higher odds of clinical Alzheimer's-type dementia (odds ratio = 6.73, 95% confidence interval = 4.18, 10.85) than pathologic Alzheimer's disease alone (odds ratio = 4.62, 95% confidence interval = 2.84, 7.52). In models examining TDP-43 stage, a dose-response relationship with clinical Alzheimer's-type dementia was observed, and a significant association was observed starting at stage 2, extension beyond the amygdala. In this large sample from almost 1000 community participants, we observed that TDP-43 proteinopathy was very common, frequently mixed with pathological Alzheimer's disease, and associated with a higher likelihood of the clinical expression of clinical Alzheimer's-type dementia but only when extended beyond the amygdala.
Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas de Ligação a DNA/metabolismo , Proteinopatias TDP-43/patologia , Idoso , Idoso de 80 Anos ou mais , Arteriolosclerose/etiologia , Arteriolosclerose/metabolismo , Arteriolosclerose/patologia , Autopsia , Infarto Encefálico/etiologia , Infarto Encefálico/metabolismo , Infarto Encefálico/patologia , Estudos de Coortes , Feminino , Humanos , Vida Independente , Masculino , Escalas de Graduação PsiquiátricaRESUMO
BACKGROUND: Arteriosclerosis is one of the most important public health issues because it is very common in developed countries and its sequelae are lethal. Lymphatic vessel insufficiency has been reported to be associated with atherogenesis. Lymphedema seems to affect progression of arteriosclerosis, but no clinical study has been reported. METHODS: Forty-eight limbs of 24 female patients with pelvic cancer-related lower extremity lymphedema (LEL) were evaluated. Cardio-ankle vascular index (CAVI), an indirect estimate of the arterial stiffness, was measured in each limb. Cardio-ankle vascular index was compared according to known arteriosclerosis risk factors including age (younger than 65 years vs 65 years), body mass index (BMI; <25 vs 25 kg/m), hypertension (HT), diabetes mellitus, hyperlipidemia (HL), and smoking, as well as according to LEL-related factors including duration of LEL (<5 years vs 5 years), pelvic irradiation, leg cellulitis, LEL index (<250 vs 250), and leg dermal backflow (LDB) stage (LDB stage 0/I vs LDB stage II/III/IV/V) using univariable analyses and multivariable analysis. RESULTS: Univariable analyses revealed statistically significant differences in CAVI between lower BMI and higher BMI [7.19 (0.75) vs 8.36 (1.24), P < 0.01], HT (-) and HT (+) [7.25 (0.81) vs 8.17 (1.29), P < 0.01], HL (-) and HL (+) [7.19 (0.74) vs 8.06 (1.27), P < 0.01], and lower LDB stage and higher LDB stage [6.87 (0.65) vs 7.76 (1.05), P < 0.01]. Multivariable analysis revealed statistically significant differences in CAVI between lower BMI and higher BMI (P < 0.01), shorter duration of LEL and longer duration of LEL [7.21 (1.04) vs 7.71 (0.97), P = 0.04], and lower LDB stage and higher LDB stage (P = 0.04) CONCLUSIONS: Higher BMI, longer duration of LEL, and higher LDB stage were independent factors associated with higher CAVI in pelvic cancer-related LEL.
Assuntos
Arteriolosclerose/etiologia , Linfedema/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteriolosclerose/diagnóstico , Feminino , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Neoplasias Pélvicas/complicações , Neoplasias Pélvicas/terapia , Fatores de Risco , Rigidez VascularRESUMO
Liver involvement in diabetes is well recognized in the form of steatohepatitis and glycogenic hepatopathy. More recently, sinusoidal fibrosis, even in the absence of steatosis, has also been suggested to be associated with diabetes (diabetic hepatosclerosis); however, case-control studies are lacking. In addition, microangiopathy (hyaline arteriolosclerosis), a well-known complication of diabetes, has not been well studied in liver. Therefore, we undertook a cross-sectional blinded study with the specific aim of evaluating the association between hepatic sinusoidal fibrosis and hepatic arteriolosclerosis (HA) with diabetes. Liver biopsy findings from 89 diabetic patients obtained between January 2006 and December 2009 were compared with those of 89 nondiabetic patients matched by age and hepatitis C virus infection status. Patients with cirrhosis, liver mass, right heart failure, significant alcohol use, or insufficient available clinical information were excluded. Medical records were reviewed for the presence of diabetes, body mass index, diabetes treatment, and comorbidities at the time of biopsy (eg, underlying liver disease, hypertension, dyslipidemia). Liver biopsies were evaluated blinded to all clinical data (including presence or absence of diabetes) for a variety of histologic features, especially patterns of fibrosis and HA. Diabetic patients had a higher average body mass index (33 vs. 30 m/kg, P=0.0039), prevalence of hypertension (78% vs. 33%, P<0.0001), and dyslipidemia (52% vs. 20%, P<0.0001). Among diabetic patients, 87% had type 2 diabetes, and 57% used insulin. Whereas sinusoidal fibrosis, with or without steatosis, was not significantly associated with the presence of diabetes, HA was significantly more prevalent among diabetic patients compared with controls: 45% versus 29% (P=0.0298). The presence of both diabetes and hypertension had a significant odds for HA: with an adjusted odds ratio of 2.632 (95% confidence interval, 1.178-5.878; P=0.0183). Biliary changes were associated with HA in some cases (10.6%).In this study, we describe the histopathologic entity of HA for the first time. It is a small-vessel complication (microangiopathy) of the liver observed mainly in patients with diabetes who also have arterial hypertension. The clinical and prognostic implications of this finding, particularly regarding liver injury, remain to be further investigated.
Assuntos
Arteriolosclerose/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Hipertensão/complicações , Fígado/irrigação sanguínea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Premature arteriosclerosis may be one of the mechanisms linking pre-diabetes mellitus (pre-DM) and cardiovascular disease. We sought to characterize premature arteriosclerosis in pre-DM using different arterial stiffness indices and to find the independent contributors of this process. We recruited 33 patients without DM, 53 patients with pre-DM, and 34 subjects with DM. Both the compliance index (CI) and stiffness index (SI) were measured. Patients with pre-DM and DM had lower CI (3.8 ± 2.1 versus 5.2 ± 3.0 units; P < 0.05 and 3.6 ± 1.8 versus 5.2 ± 3.0 units; P < 0.05, respectively) and higher SI (8.0 ± 2.0 versus 6.7 ± 1.6 m/s; P < 0.01 and 9.4 ± 2.3 versus 6.7 ± 1.6 m/s; P < 0.001, respectively) than patients without DM. Using multivariate linear regression analysis, age, heart rate, and HOMA index were independent determinants for SI (whole model: R(2) = 0.47, P < 0.001), whereas male gender, hsCRP, and HOMA index were independent determinants for CI (whole model: R(2) = 0.34, P < 0.01). The HOMA index was an independent determinant for arterial stiffness. Increased insulin resistance may associate with increased arterial stiffness at peripheral arteries in pre-DM patients.
Assuntos
Arteriolosclerose , Glicemia , Estado Pré-Diabético , Rigidez Vascular , Adiponectina/análise , Adulto , Fatores Etários , Arteriolosclerose/etiologia , Arteriolosclerose/metabolismo , Arteriolosclerose/fisiopatologia , Glicemia/análise , Glicemia/metabolismo , Proteína C-Reativa/análise , Estudos Transversais , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Frequência Cardíaca , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/complicações , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/fisiopatologia , Análise de Regressão , Fatores de Risco , Fatores SexuaisRESUMO
AIM: Complement C3 (C3) is one of the major mediators of inflammation. Serum C3 has been shown to be correlated with the presence of atherosclerosis. We examined whether the serum C3 level might be correlated with the severity of renal arteriolosclerosis in patients with chronic kidney disease (CKD). METHODS: Non-diabetic CKD (stages 1-3) patients who underwent renal biopsy were enrolled in this study. Renal arteriolosclerosis was defined by the presence of hyaline changes and vessel wall thickening in the renal biopsy specimens. We examined whether the serum C3 level might be correlated with the severity of renal arteriolosclerosis in CKD patients. RESULTS: A total of 208 CKD patients (age 36.0±13.6 years; 94 male) who underwent renal biopsy were included. Univariate analysis showed that the serum C3 level was positively correlated with age, body mass index, blood pressure and the serum triglyceride, LDL cholesterol and CRP (p<0.001). The serum C3 level was also inversely correlated with serum HDL cholesterol (p<0.001). Multiple regression analysis identified that the serum C3 (p=0.043) as well as age (p<0.001), serum uric acid (p=0.009) and eGFR (p= 0.025) were independently associated with the severity of renal arteriolosclerosis. CONCLUSION: Our results suggest that the serum C3 level is a reliable marker of renal arteriolosclerosis. Components of metabolic syndrome were also correlated with the serum C3 level. Inflammation or metabolic syndrome may contribute to CKD through influencing the rate of progression of renal arteriolosclerosis.
Assuntos
Arteriolosclerose/diagnóstico , Biomarcadores/sangue , Complemento C3/metabolismo , Insuficiência Renal Crônica/complicações , Adulto , Arteriolosclerose/sangue , Arteriolosclerose/etiologia , Pressão Sanguínea , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Prognóstico , Insuficiência Renal Crônica/sangue , Fatores de Risco , Triglicerídeos/sangueRESUMO
OBJECTIVE: The authors aimed to describe the atherosclerotic lesions of the cerebral arterioles as a substrate of their rupture and bleeding. METHODS: The study was performed on the brain of nine Caucasian fetal victims of intra- and periventricular hemorrhage, all grade IV, and nine control cases. RESULTS: In the nine victims of hemorrhage, the arteriolar wall structure was altered, focally transformed into a deposit of amorphous eosinophilic material. Such changes often affected the full thickness of the wall causing rupture and hemorrhage. In eight of these cases and in two victims of the control group, the mothers were heavy cigarette smokers (15-20 cigarettes/day) before and during pregnancy. CONCLUSION: The authors conclude that intra- and periventricular hemorrhage can be ascribed to the toxic effects of prenatal absorption of nicotine.
Assuntos
Arteriolosclerose/etiologia , Hemorragias Intracranianas/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fumar/efeitos adversos , Adulto , Arteriolosclerose/patologia , Feminino , Humanos , Hemorragias Intracranianas/patologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Adulto JovemRESUMO
A 17-year-old girl was admitted to our hospital with severe refractory hypertension evolving over approximately 4 years. Despite not having the resources to identify plasma-renin levels and using standard imaging techniques, a juxtaglomerular cell tumor was suspected and was histologically confirmed after surgical excision. This is a potentially lethal condition if left untreated and surgical excision is curative. The benign nature of the tumor is emphasized and its chemical, radiological and microscopic appearance discussed according to the literature. To the best of our knowledge, this is the first reported case of a patient surviving a cerebrovascular accident associated with a juxtaglomerular cell tumor.
Assuntos
Arteriolosclerose/etiologia , Carcinoma de Células Renais/complicações , Hipertensão/etiologia , Sistema Justaglomerular/patologia , Neoplasias Renais/complicações , Insuficiência Renal/etiologia , Adolescente , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Imageamento por Ressonância Magnética , Nefrectomia , Doenças Raras , Resultado do Tratamento , UltrassonografiaRESUMO
The advanced glycation end-products (AGEs) constitute a class of heterogeneous molecules formed by amino-carbonyl reactions of a non-enzymatic nature, which occur at an accelerated rate in the hyperglycemic state of diabetes. Considered important pathogenic mediators of diabetic complications, AGEs are capable of irreversibly modifying the chemical properties and functions of diverse biological structures. In this review, recent data from literature is presented describing the pathways of AGEs formation, their metabolism, the main mechanisms of action of these substances in the triggering of pathological processes associated with diabetes, as well as methods of AGEs determination in biological samples. This text also points to new perspectives in anti-AGE therapies, an example of which is the studies involved with the action of natural compounds of food, which can represent a potential coadjuvant therapy for people with diabetes or other pathologies associated with the degenerative accumulation of AGEs.
Assuntos
Arteriolosclerose/etiologia , Angiopatias Diabéticas/etiologia , Produtos Finais de Glicação Avançada/fisiologia , Antioxidantes/uso terapêutico , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Retinopatia Diabética/etiologia , Alimentos , Produtos Finais de Glicação Avançada/análise , Produtos Finais de Glicação Avançada/antagonistas & inibidores , HumanosRESUMO
Os produtos finais da glicação avançada (AGEs [do inglês, Advanced Glycation End-products]) constituem uma classe de moléculas heterogêneas formadas a partir de reações aminocarbonilo de natureza não-enzimática, que ocorrem aceleradamente no estado hiperglicêmico do diabetes. Considerados importantes mediadores patogênicos das complicações diabéticas, os AGEs são capazes de modificar, irreversivelmente, as propriedades químicas e funcionais das mais diversas estruturas biológicas. Na presente revisão, são apresentados os dados recentes da literatura que descrevem as vias de formação de AGEs, seu metabolismo, os principais mecanismos de ação dessas substâncias no desencadeamento dos processos patológicos, bem como os métodos de determinação de AGEs em amostras biológicas. Este artigo aponta, ainda, novas perspectivas de terapias anti-AGEs, a exemplo de estudos envolvendo a ação de compostos naturais dos alimentos, que podem oferecer potencial terapêutico para os portadores de diabetes ou de outras patologias associadas ao acúmulo degenerativo de AGEs.
The advanced glycation end-products (AGEs) constitute a class of heterogeneous molecules formed by amino-carbonyl reactions of a non-enzymatic nature, which occur at an accelerated rate in the hyperglycemic state of diabetes. Considered important pathogenic mediators of diabetic complications, AGEs are capable of irreversibly modifying the chemical properties and functions of diverse biological structures. In this review, recent data from literature is presented describing the pathways of AGEs formation, their metabolism, the main mechanisms of action of these substances in the triggering of pathological processes associated with diabetes, as well as methods of AGEs determination in biological samples. This text also points to new perspectives in anti-AGE therapies, an example of which is the studies involved with the action of natural compounds of food, which can represent a potential coadjuvant therapy for people with diabetes or other pathologies associated with the degenerative accumulation of AGEs.
Assuntos
Humanos , Arteriolosclerose/etiologia , Angiopatias Diabéticas/etiologia , /fisiologia , Antioxidantes/uso terapêutico , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Retinopatia Diabética/etiologia , Alimentos , /análise , /antagonistas & inibidoresRESUMO
BACKGROUND: The apo B/apo A-I ratio represents the balance between atherogenic particles, rich in apo B, and the antiatherogenic ones, apo A-I rich. This study investigated the association between atherosclerotic diseases in different anatomical sites and apo B/apo A-I ratio. METHODS: Lipids, lipoproteins, and apolipoproteins A-I and B were assessed in 30 subjects with coronary artery disease (CAD), 26 with ischemic stroke (IS), 30 with peripheral arterial obstructive disease (PAOD), and 38 healthy subjects (controls). RESULTS: HDLc and Apo A-I were significantly lower in PAOD and CAD groups, respectively, than in other groups. Significantly higher levels of triglycerides were observed for CAD and PAOD groups than for controls. Apo B was significantly higher in IS group than in control and PAOD groups. The apo B/apo A-I ratio showed significantly higher in CAD and IS groups when compared to control and PAOD groups (p < 0.001). CONCLUSION: The apo B/apo A-I ratio was important for identifying an increased trend for coronary and cerebral atherosclerosis. In spite of the increased trend for apo B/apo A-I ratio in IS and CAD groups, the studied variables cannot be considered in an isolated way, given as those parameters were analyzed together by a binary logistic regression, no association has been demonstrated.
Assuntos
Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Arteriolosclerose/sangue , Doença da Artéria Coronariana/sangue , Doenças Vasculares Periféricas/sangue , Acidente Vascular Cerebral/sangue , Adolescente , Adulto , Idoso , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/etiologia , Arteriolosclerose/etiologia , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/etiologia , Criança , HDL-Colesterol/sangue , Doença da Artéria Coronariana/etiologia , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Doenças Vasculares Periféricas/etiologia , Fatores de Risco , Fumar , Triglicerídeos/sangueRESUMO
BACKGROUND: The apo B/apo A-I ratio represents the balance between atherogenic particles, rich in apo B, and the antiatherogenic ones, apo A-I rich. This study investigated the association between atherosclerotic diseases in different anatomical sites and apo B/apo A-I ratio. METHODS: Lipids, lipoproteins, and apolipoproteins A-I and B were assessed in 30 subjects with coronary artery disease (CAD), 26 with ischemic stroke (IS), 30 with peripheral arterial obstructive disease (PAOD), and 38 healthy subjects (controls). RESULTS: HDLc and Apo A-I were significantly lower in PAOD and CAD groups, respectively, than in other groups. Significantly higher levels of triglycerides were observed for CAD and PAOD groups than for controls. Apo B was significantly higher in IS group than in control and PAOD groups. The apo B/apo A-I ratio showed significantly higher in CAD and IS groups when compared to control and PAOD groups (p < 0.001). CONCLUSION: The apo B/apo A-I ratio was important for identifying an increased trend for coronary and cerebral atherosclerosis. In spite of the increased trend for apo B/apo A-I ratio in IS and CAD groups, the studied variables cannot be considered in an isolated way, given as those parameters were analyzed together by a binary logistic regression, no association has been demonstrated.
INTRODUÇÃO: O índice apo B/apo A-I representa o balanço entre partículas de colesterol potencialmente aterogênicas ricas em apo B e partículas anti-aterogênicas ricas em apo A-I. O objetivo deste estudo foi investigar a associação entre doenças ateroscleróticas em diferentes sítios anatômicos e o índice apo B/apo A-I. MÉTODOS: Lípides, lipoproteínas e apolipoproteínas A-I e B foram quantificados em 30 indivíduos apresentando doença arterial coronariana (DAC), 26 com acidente vascular cerebral (AVC), 34 apresentando doença arterial obstrutiva periférica (DAOP) e 38 indivíduos hígidos (grupo controle). RESULTADOS: HDLc e apo A-I apresentaram-se significativamente mais baixos nos grupos DAOP e DAC, respectivamente, quando comparados com os demais grupos. Níveis de triglicérides foram significativamente mais elevados nos grupos DAC e PAOD quando comparados com o grupo controle. Apo B foi significativamente mais elevada no grupo AVC quando comparado com os grupos controle e DAOP. O índice apo B/apo A-I se mostrou significativamente elevado nos grupos DAC e AVC quando comparados com os demais (p < 0,001). CONCLUSÃO: O índice apo B/apo A-I foi importante para identificar uma tendência aumentada para aterosclerose coronariana e cerebral. No entanto, os parâmetros avaliados não podem ser considerados de forma isolada, considerando que nenhuma associação foi demonstrada quando os dados foram analisados pelo modelo de regressão logística binária.
Assuntos
Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Arteriolosclerose/sangue , Doença da Artéria Coronariana/sangue , Doenças Vasculares Periféricas/sangue , Acidente Vascular Cerebral/sangue , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/etiologia , Arteriolosclerose/etiologia , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/etiologia , HDL-Colesterol/sangue , Doença da Artéria Coronariana/etiologia , Métodos Epidemiológicos , Linhagem , Doenças Vasculares Periféricas/etiologia , Fatores de Risco , Fumar , Triglicerídeos/sangueRESUMO
BACKGROUND: Previous studies have demonstrated that macrophages and CD4+ T lymphocytes play pivotal roles in collateral development. Indirect evidence suggests that CD8+ T cells also play a role. Thus, after acute cerebral ischemia, CD8+ T cells infiltrate the perivascular space and secrete interleukin-16 (IL-16), a potent chemoattractant for monocytes and CD4+ T cells. We tested whether CD8+ T lymphocytes contribute to collateral vessel development and whether the lack of circulating CD8+ T cells prevents IL-16 expression, impairs CD4+ mononuclear cell recruitment, and reduces collateral vessel growth after femoral artery ligation in CD8(-/-) mice. METHODS AND RESULTS: After surgical excision of the femoral artery, laser Doppler perfusion imaging demonstrated reduced blood flow recovery in CD8(-/-) mice compared with C57/BL6 mice (ischemic/nonischemic limb at day 28, 0.66+/-0.04 versus 0.87+/-0.04, respectively; P<0.01). This resulted in greater calf muscle atrophy (mean fiber area, 785+/-68 versus 1067+/-69 microm2, respectively; P<0.01) and increased fibrotic tissue content (10.8+/-1.2% versus 7+/-1%, respectively; P<0.01). Moreover, CD8(-/-) mice displayed reduced IL-16 expression and decreased CD4+ T-cell recruitment at the site of collateral vessel development. Exogenous CD8+ T cells, infused into CD8(-/-) mice immediately after femoral artery ligation, selectively homed to the ischemic hind limb and expressed IL-16. The restoration of IL-16 expression resulted in significant CD4+ mononuclear cell infiltration of the ischemic limb, faster blood flow recovery, and reduced hindlimb muscle atrophy/fibrosis. When exogenous CD8+ T cells deficient in IL-16 (IL-16(-/-)) were infused into CD8(-/-) mice immediately after femoral artery ligation, they selectively homed to the ischemic hind limb but were unable to recruit CD4+ mononuclear cells and did not improve blood flow recovery. CONCLUSIONS: These results demonstrate that CD8+ T cells importantly contribute to the early phase of collateral development. After femoral artery ligation, CD8+ T cells infiltrate the site of collateral vessel growth and recruit CD4+ mononuclear cells through the expression of IL-16. Our study provides further evidence of the significant role of the immune system in modulating collateral development in response to peripheral ischemia.