RESUMO
Scattered tubular-like cells (STCs) contribute to repair neighboring injured renal tubular cells. Mitochondria mediate STC biology and function but might be injured by the ambient milieu. We hypothesized that the microenviroment induced by the ischemic and metabolic components of renovascular disease impairs STC mitochondrial structure and function in swine, which can be attenuated with mitoprotection. CD24+/CD133+ STCs were quantified in pig kidneys after 16 wk of metabolic syndrome (MetS) or lean diet (Lean) with or without concurrent renal artery stenosis (RAS) (n = 6 each). Pig STCs were isolated and characterized, and mitochondrial structure, membrane potential, and oxidative stress were assessed in cells untreated or incubated with the mitoprotective drug elamipretide (1 nM for 6 h). STC-protective effects were assessed in vitro by their capacity to proliferate and improve viability of injured pig tubular epithelial cells. The percentage of STCs was higher in MetS, Lean + RAS, and MetS + RAS kidneys compared with Lean kidneys. STCs isolated from Lean + RAS and MetS + RAS pigs showed mitochondrial swelling and decreased matrix density, which were both restored by mitoprotection. In addition, mitochondrial membrane potential and ATP production were reduced and production of reactive oxygen species elevated in MetS, Lean + RAS, and MetS + RAS STCs. Importantly, mitoprotection improved mitochondrial structure and function as well as the capacity of MetS + RAS STCs to repair injured tubular cells in vitro. Renovascular disease in swine is associated with a higher prevalence of STCs but induces structural and functional alterations in STC mitochondria, which impair their reparative potency. These observations suggest a key role for mitochondria in the renal reparative capacity of STCs.
Assuntos
Túbulos Renais/citologia , Mitocôndrias/patologia , Obstrução da Artéria Renal/etiologia , Ração Animal , Animais , Colesterol na Dieta , Carboidratos da Dieta , Feminino , Obstrução da Artéria Renal/patologia , Circulação Renal , SuínosRESUMO
Metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. The potential involvement of podocyte damage in early MetS remains unclear. Mitochondrial dysfunction is an important determinant of renal damage, but whether it contributes to MetS-related podocyte injury remains unknown. Domestic pigs were studied after 16 wk of diet-induced MetS, MetS treated with the mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg·kg-1·day-1 sc) for the last month of diet, and lean controls (n = 6 pigs/group). Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured using multidetector computed tomography, and podocyte and mitochondrial injury were measured by light and electron microscopy. Urinary levels of podocyte-derived extracellular vesicles (pEVs; nephrin positive/podocalyxin positive) were characterized by flow cytometry. Body weight, blood pressure, RBF, and GFR were elevated in MetS. Glomerular size and glomerular injury score were also elevated in MetS and decreased after ELAM treatment. Evidence of podocyte injury, impaired podocyte mitochondria, and foot process width were all increased in MetS but restored with ELAM. The urinary concentration of pEVs was elevated in MetS pigs and directly correlated with renal dysfunction, glomerular injury, and fibrosis and inversely correlated with glomerular nephrin expression. Additionally, pEV numbers were elevated in the urine of obese compared with lean human patients. Early MetS induces podocyte injury and mitochondrial damage, which can be blunted by mitoprotection. Urinary pEVs reflecting podocyte injury might represent early markers of MetS-related kidney disease and a novel therapeutic target.
Assuntos
Vesículas Extracelulares/ultraestrutura , Síndrome Metabólica/patologia , Mitocôndrias/fisiologia , Podócitos/ultraestrutura , Animais , Dieta , Dieta Hiperlipídica , Feminino , Frutose/administração & dosagem , Taxa de Filtração Glomerular , Humanos , Rim/irrigação sanguínea , Rim/patologia , Rim/fisiopatologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/etiologia , Mitocôndrias/ultraestrutura , Obesidade/urina , Oligopeptídeos/uso terapêutico , Podócitos/efeitos dos fármacos , Circulação Renal , Sus scrofa , UrinaRESUMO
BACKGROUND: A growing body of evidence suggests an association between lower serum 25-hydroxy vitamin D (25(OH)VitD) levels and adverse cardiovascular events. Patients with type 2 diabetes mellitus (T2DM) are at increased risk for developing coronary heart disease (CHD). 25-Hydroxy vitamin D deficiency is highly prevalent, especially among patients with T2DM. This study aimed to evaluate the predictive value of serum 25(OH)VitD in improvement of CHD risk stratification in patients with T2DM. METHODS: In an open cohort, community-dwelling T2DM patients were followed up for first CHD event. Patients were divided into 4 categories, based on 25(OH)VitD quartiles. Cox regression analysis was used to obtain hazard ratios. RESULTS: A total number of 2,607 T2DM patients were followed up for median time of 8.5 years. During follow-up, 299 patients experienced CHD events. Patients in the lowest quartile experienced more CHD events. Adjusted hazard ratios (95% CI) for developing CHD events were 0.77 (0.55-1.07) for second quartile, 0.52 (0.38-0.73) for third quartile, and 0.43 (0.31-0.60) for fourth quartile, compared with the first quartile. The incidence rate decreased as serum 25(OH)VitD increased, which remained significant after stepwise adjustments (P value for trend ≤.001). Addition of 25(OH)VitD to traditional risk factors in Framingham Risk Score successfully reclassified 29% of study population. CONCLUSIONS: Serum 25(OH)VitD is an independent predictor of future adverse CHD events in patients with T2DM. Addition of 25(OH)VitD status to Framingham Risk Score improves CHD risk prediction in patients with T2DM.
Assuntos
Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Medição de Risco/métodos , Vitamina D/análogos & derivados , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Seguimentos , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Vitamina D/farmacocinética , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/etiologia , Vitaminas/farmacocinéticaRESUMO
Calcium is a key regulator of cell dynamics. Dysregulation of its cytosolic concentration is implicated in the pathophysiology of several diseases. This study aimed to assess the effects of calcium on the network of membrane cytoskeletal proteins. Erythrocyte membranes were obtained from eight healthy donors and incubated with 250 µM and 1.25 mM calcium solutions. Membrane cytoskeletal proteins were quantified using SDS-PAGE at baseline and after 3 and 5 days of incubation. Supra-physiologic concentrations of calcium (1.25 mM) induced a significant proteolysis in membrane cytoskeletal proteins, compared with magnesium (p < 0.001). Actin exhibited the highest sensitivity to calcium-induced proteolysis (6.8 ± 0.3 vs. 5.3 ± 0.6, p < 0.001), while spectrin (39.9 ± 1.0 vs. 40.3 ± 2.0, p = 0.393) and band-6 (6.3 ± 0.3 vs. 6.8 ± 0.8, p = 0.191) were more resistant to proteolysis after incubation with calcium in the range of endoplasmic reticulum concentrations (250 µM). Aggregation of membrane cytoskeletal proteins was determined after centrifugation and was significantly higher after incubation with calcium ions compared with control, EDTA and magnesium solutions (p < 0.001). In a supra-physiologic range of 1.25-10 mM of calcium ions, there was a nearly perfect linear relationship between calcium concentration and aggregation of erythrocyte membrane cytoskeletal proteins (R(2) = 0.971, p < 0.001). Our observation suggests a strong interaction between calcium ions and membrane cytoskeletal network. Cumulative effects of disrupted calcium homeostasis on cytoskeletal proteins need to be further investigated at extended periods of time in disease states.
Assuntos
Actinas/metabolismo , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Cálcio/farmacologia , Proteínas do Citoesqueleto/metabolismo , Membrana Eritrocítica/metabolismo , Espectrina/metabolismo , Eletroforese em Gel de Poliacrilamida , Membrana Eritrocítica/efeitos dos fármacos , Humanos , Técnicas In VitroRESUMO
BACKGROUND: 8-iso-PGF2α is a family of PGF2α that could be offered as a non-invasive tool to represent in vivo oxidation status, as a link between oxidative milieus and vascular dysfunction. METHODS: A total of 45 patients with type 2 diabetes and 45 healthy adults were studied in this cross-sectional analysis. Blood samples were collected to measure the level of lipid profile, oxidative stress, and glycemic control indices. The sensitivity and specificity of 8-iso-PGF2α as a screening test were analyzed in the cut-off range 252 - 377.5 pg/mL and the corresponding receiver operating characteristics (ROC) were plotted to assess performance of the test. RESULTS: 8-iso-PGF2α level was significantly higher in the diabetic group (439.11 pg/mL ± 181.13 vs. 380.93 pg/mL ± 146.52). After adjustments for age, gender, and body mass index (BMI), linear regression analysis revealed that homeostasis model assessment of insulin resistance (HOMA-IR), blood pressure, fasting blood sugar (FBS), serum creatinine, insulin, oxLDL, and CRP levels are directly correlated with 8-iso-PGF2α in the 25% - 75% quartiles. Moreover, their mean levels were higher in quartiles with greater 8-iso-PGF2α levels. The cut-offs showing the best equilibrium between sensitivity and specificity approached 269.5 pg/mL with 83% and 62.5% sensitivity and specificity, respectively. CONCLUSIONS: Our study provides evidence for the application of serum 8-isoPGF2α in the 25 - 75% quartile ranges to screen for the severity of oxidative reactions and glycemic control in vivo without need for any further in vitro enzymatic reactions, with higher levels, reflecting more severe oxidation and poor glycemic control.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Dinoprosta/análogos & derivados , Hemoglobinas Glicadas/análise , Estresse Oxidativo , Idoso , Área Sob a Curva , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Dinoprosta/sangue , Feminino , Humanos , Mediadores da Inflamação/sangue , Insulina/sangue , Modelos Lineares , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROCRESUMO
Importance: Wearable devices may be able to improve cardiovascular health, but the current adoption of these devices could be skewed in ways that could exacerbate disparities. Objective: To assess sociodemographic patterns of use of wearable devices among adults with or at risk for cardiovascular disease (CVD) in the US population in 2019 to 2020. Design, Setting, and Participants: This population-based cross-sectional study included a nationally representative sample of the US adults from the Health Information National Trends Survey (HINTS). Data were analyzed from June 1 to November 15, 2022. Exposures: Self-reported CVD (history of heart attack, angina, or congestive heart failure) and CVD risk factors (≥1 risk factor among hypertension, diabetes, obesity, or cigarette smoking). Main Outcomes and Measures: Self-reported access to wearable devices, frequency of use, and willingness to share health data with clinicians (referred to as health care providers in the survey). Results: Of the overall 9303 HINTS participants representing 247.3 million US adults (mean [SD] age, 48.8 [17.9] years; 51% [95% CI, 49%-53%] women), 933 (10.0%) representing 20.3 million US adults had CVD (mean [SD] age, 62.2 [17.0] years; 43% [95% CI, 37%-49%] women), and 5185 (55.7%) representing 134.9 million US adults were at risk for CVD (mean [SD] age, 51.4 [16.9] years; 43% [95% CI, 37%-49%] women). In nationally weighted assessments, an estimated 3.6 million US adults with CVD (18% [95% CI, 14%-23%]) and 34.5 million at risk for CVD (26% [95% CI, 24%-28%]) used wearable devices compared with an estimated 29% (95% CI, 27%-30%) of the overall US adult population. After accounting for differences in demographic characteristics, cardiovascular risk factor profile, and socioeconomic features, older age (odds ratio [OR], 0.35 [95% CI, 0.26-0.48]), lower educational attainment (OR, 0.35 [95% CI, 0.24-0.52]), and lower household income (OR, 0.42 [95% CI, 0.29-0.60]) were independently associated with lower use of wearable devices in US adults at risk for CVD. Among wearable device users, a smaller proportion of adults with CVD reported using wearable devices every day (38% [95% CI, 26%-50%]) compared with overall (49% [95% CI, 45%-53%]) and at-risk (48% [95% CI, 43%-53%]) populations. Among wearable device users, an estimated 83% (95% CI, 70%-92%) of US adults with CVD and 81% (95% CI, 76%-85%) at risk for CVD favored sharing wearable device data with their clinicians to improve care. Conclusions and Relevance: Among individuals with or at risk for CVD, fewer than 1 in 4 use wearable devices, with only half of those reporting consistent daily use. As wearable devices emerge as tools that can improve cardiovascular health, the current use patterns could exacerbate disparities unless there are strategies to ensure equitable adoption.
Assuntos
Doenças Cardiovasculares , Hipertensão , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Hipertensão/epidemiologia , Fatores de Risco , Obesidade/epidemiologiaRESUMO
BACKGROUND: Renovascular hypertension (RVH) often manifest with metabolic syndrome (MetS) as well. Coexisting MetS and hypertension increases cardiovascular morbidity and mortality, but the mechanisms underlying cardiac injury remain unknown. We hypothesized that superimposition of MetS induces myocardial mitochondrial damage, leading to cardiac injury and dysfunction in swine RVH. METHODS: Pigs were studied after 16 weeks of diet-induced MetS with or without RVH (unilateral renal artery stenosis), and Lean controls (n = 6 each). Systolic and diastolic cardiac function were assessed by multidetector CT, and cardiac mitochondrial morphology (electron microscopy) and myocardial function in tissue and isolated mitochondria. RESULTS: Body weight was similarly higher in MetS groups vs. Lean. RVH groups achieved significant stenosis and developed hypertension. Mitochondrial matrix density and adenosine triphosphate production were lower and H2O2 production higher in RVH groups vs. Lean and MetS. Lean + RVH (but not MetS + RVH) activated mitophagy, which was associated with decreased myocardial expression of mitophagy-related microRNAs. MetS groups exhibited higher numbers of intermitochondrial junctions, which could have prevented membrane depolarization/activation of mitophagy in MetS + RVH. Cardiac fibrosis, hypertrophy (increased left ventricular muscle mass), and diastolic function (decreased E/A ratio) were greater in MetS + RVH vs. Lean + RVH. CONCLUSIONS: MetS+RVH induces myocardial mitochondrial damage and dysfunction. MetS + RVH failed to activate mitophagy, resulting in greater cardiac remodeling, fibrosis, and diastolic dysfunction. Mitochondrial injury and impaired mitophagy may constitute important mechanisms and therapeutic targets to ameliorate cardiac damage and dysfunction in patients with coexisting MetS and RVH.
Assuntos
Cardiopatias , Traumatismos Cardíacos , Hipertensão Renovascular , Síndrome Metabólica , Animais , Cardiopatias/etiologia , Cardiopatias/veterinária , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/veterinária , Hipertensão Renovascular/complicações , Hipertensão Renovascular/veterinária , Síndrome Metabólica/complicações , Síndrome Metabólica/veterinária , Mitocôndrias Cardíacas , SuínosRESUMO
BACKGROUND: Mitochondria modulate endothelial cell (EC) function, but may be damaged during renal disease. We hypothesized that the ischemic and metabolic constituents of swine renovascular disease (RVD) induce mitochondrial damage and impair the function of renal artery ECs. METHODS: Pigs were studied after 16 weeks of metabolic syndrome (MetS), renal artery stenosis (RAS), or MetS + RAS, and Lean pigs served as control (n = 6 each). Mitochondrial morphology, homeostasis, and function were measured in isolated primary stenotic-kidney artery ECs. EC functions were assessed in vitro, whereas vasoreactivity of renal artery segments was characterized in organ baths. RESULTS: Lean + RAS and MetS + RAS ECs showed increased mitochondrial area and decreased matrix density. Mitochondrial biogenesis was impaired in MetS and MetS + RAS compared with their respective controls. Mitochondrial membrane potential similarly decreased in MetS, Lean + RAS, and MetS + RAS groups, whereas production of reactive oxygen species increased in MetS vs. Lean, but further increased in both RAS groups. EC tube formation was impaired in MetS, RAS, and MetS + RAS vs. Lean, but EC proliferation and endothelial-dependent relaxation of renal artery segments were blunted in MetS vs. Lean, but further attenuated in Lean + RAS and MetS + RAS. CONCLUSIONS: MetS and RAS damage mitochondria in pig renal artery ECs, which may impair EC function. Coexisting MetS and RAS did not aggravate EC mitochondrial damage in the short time of our in vivo studies, suggesting that mitochondrial injury is associated with impaired renal artery EC function.
Assuntos
Células Endoteliais/metabolismo , Endotélio Vascular/fisiopatologia , Hipertensão Renovascular/metabolismo , Mitocôndrias/metabolismo , Artéria Renal/metabolismo , Vasodilatação/fisiologia , Animais , Modelos Animais de Doenças , Células Endoteliais/patologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Hipertensão Renovascular/patologia , Hipertensão Renovascular/fisiopatologia , Potencial da Membrana Mitocondrial/fisiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Mitocôndrias/patologia , Óxido Nítrico Sintase Tipo III/metabolismo , Distribuição Aleatória , Espécies Reativas de Oxigênio/metabolismo , Artéria Renal/patologia , Artéria Renal/fisiopatologia , Obstrução da Artéria Renal/metabolismo , Obstrução da Artéria Renal/patologia , Sus scrofa , Suínos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: Renovascular disease (RVD) produces chronic underperfusion of the renal parenchyma and progressive ischemic injury. Metabolic abnormalities often accompany renal ischemia, and are linked to poorer renal outcomes. However, the mechanisms of injury in kidneys exposed to the ischemic and metabolic components of RVD are incompletely understood. We hypothesized that coexisting renal artery stenosis (RAS) and metabolic syndrome (MetS) would exacerbate mitochondrial damage, aggravating poststenotic kidney injury in swine. METHODS: Domestic pigs were studied after 16 weeks of either standard diet (Lean) or high-fat/high-fructose (MetS) with or without superimposed RAS (nâ=â6 each). Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed in vivo with multidetector-CT, and renal tubular mitochondrial structure, homeostasis and function and renal injury ex vivo. RESULTS: Both RAS groups achieved significant stenosis. Single-kidney RBF and GFR were higher in MetS compared with Lean, but decreased in Lean+RAS and MetS+RAS vs. their respective controls. MetS and RAS further induced changes in mitochondrial structure, dynamics, and function, and their interaction (dietâ×âischemia) decreased matrix density, mitophagy, and ATP production, and lead to greater renal fibrosis. CONCLUSION: Coexisting RAS and MetS synergistically aggravate mitochondrial structural damage and dysfunction, which may contribute to structural injury and dysfunction in the poststenotic kidney. These observations suggest that mitochondrial damage precedes loss of renal function in experimental RVD, and position mitochondria as novel therapeutic targets in these patients.
Assuntos
Rim/patologia , Síndrome Metabólica/complicações , Mitocôndrias/patologia , Obstrução da Artéria Renal/complicações , Animais , Feminino , Taxa de Filtração Glomerular/fisiologia , Rim/metabolismo , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Mitocôndrias/metabolismo , Obstrução da Artéria Renal/metabolismo , Obstrução da Artéria Renal/patologia , Circulação Renal , Sus scrofa , SuínosRESUMO
INTRODUCTION: Transplantation of autologous mesenchymal stem cells (MSCs) has been shown to attenuate renal injury and dysfunction in several animal models, and its efficacy is currently being tested in clinical trials for patients with renal disease. Accumulating evidence indicates that MSCs release extracellular vesicles (EVs) that deliver genes, microRNAs and proteins to recipient cells, acting as mediators of MSC paracrine actions. In this context, it is critical to characterize the MSC-derived EV cargo to elucidate their potential contribution to renal repair. In recent years, researchers have performed high-throughput sequencing and proteomic analysis to detect and identify genes, microRNAs, and proteins enriched in MSC-derived EVs. CONCLUSION: The present review summarizes the current knowledge of the MSC-derived EV secretome to shed light into the mechanisms mediating MSC renal repair, and discusses preclinical and clinical studies testing the efficacy of MSC-derived EVs for treating renal disease.
Assuntos
Vesículas Extracelulares/transplante , Nefropatias/terapia , Transplante de Rim , Transplante de Células-Tronco Mesenquimais , Proliferação de Células/genética , Exossomos/transplante , Humanos , Rim/patologia , Nefropatias/fisiopatologia , Células-Tronco Mesenquimais/citologiaRESUMO
BACKGROUND: Both metformin and sulfonylurea (SU) drugs are among the most widely-used anti-hyperglycemic medications in patients with type 2 diabetes mellitus (T2DM). Previous studies have shown that treatment with SUs might be associated with decreased survival compared with metformin. This study aimed to evaluate all-cause and cardiovascular mortality rates between glyburide and metformin in patients diagnosed with T2DM. METHODS: This was a cohort study on 717 patients with T2DM (271 undergoing monotherapy with glyburide and 446 with metformin). Data were gathered from 2001 to 2014. All-cause and cardiovascular mortality were end-points. RESULTS: During the follow-up, 24 deaths were identified, of which 13 were cardiovascular in nature. The group with glyburide monotherapy had greater all-cause mortality (17 (6.3%) in glyburide vs. 7 (1.6%) in metformin, P = 0.001) and cardiovascular mortality (11 (4.1%) in glyburide vs. 2 (0.4%) in metformin; P = 0.001). Metformin was more protective than glyburide for both all-cause (HR: 0.27 [0.10 - 0.73] P-value = 0.01) and cardiovascular mortality (HR: 0.12 [0.20 - 0.66], P-value = 0.01) after multiple adjustments for cardiovascular risk factors. Among adverse cardiovascular events, non-fatal MI was higher in glyburide compared to metformin monotherapy group (3.2% vs. 0.8%; P-value = 0.03), but not coronary artery bypass grafting (P-value = 0.85), stenting (P-value = 0.69), need for angiography (P-value = 0.24), CCU admission (P-value = 0.34) or cerebrovascular accident (P-value = 0.10). CONCLUSION: Treatment with glyburide is associated with increased all-cause and cardiovascular mortality in patients with T2DM.
Assuntos
Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Idoso , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Estudos de Coortes , Angiografia Coronária/estatística & dados numéricos , Ponte de Artéria Coronária/estatística & dados numéricos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/cirurgia , Unidades de Cuidados Coronarianos/estatística & dados numéricos , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/mortalidade , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidadeRESUMO
We aimed to study the relation between plasma levels of stress-induced heat shock protein 70 (HSPA1A) with plasminogen activator inhibitor-1 (PAI-1) and high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1), and HDL-C/Apo-A1 ratio. In a matched case-control study on patients with diabetes (40 patients with albuminuria and 40 without albuminuria matched for age, sex, and body mass index), we observed that plasma levels of HSPA1A and PAI-1 are increased in patients with albuminuria (0.55 ± 0.02 vs. 0.77 ± 0.04 ng/ml, p value <0.001 for HSPA1A; 25.9 ± 2 vs. 31.8 ± 2.4 ng/ml, p value <0.05 for PAI-1). There was a significant correlation between HSPA1A and PAI-1 in diabetic patients without albuminuria (r = 0.28; p value = 0.04), but not in those with albuminuria (r = 0.07; p value = 0.63). No association was found between HSPA1A and HDL-C, between HSPA1A and Apo-A1, or between HSPA1A and HDL-C/Apo-A1 ratio. We concluded that there is a direct correlation between plasma HSPA1A and PAI-1 levels in patients with diabetes, which is lost when they develop albuminuria.
Assuntos
Albuminúria/sangue , Albuminúria/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Proteínas de Choque Térmico HSP70/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Apolipoproteína A-I/sangue , Estudos de Casos e Controles , HDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Vitamin D deficiency is proposed as a risk factor for coronary heart disease (CHD). An inverse relation was observed between serum 25-Hydroxy-Vitamin-D level and incidence of hypertension. This study aimed to evaluate the predictive value of serum 25-Hydroxy-Vitamin-D in improvement of CHD risk-stratification in patients with hypertension. METHODS: In this cohort, we followed 1586 patients with essential hypertension (1078 diabetic and 508 non-diabetic) for 8.5 years. Physician-adjudicated first hard CHD event was the primary outcome. Cox regression analysis was used to investigate the association between 25-Hydroxy-Vitamin-D quartiles and incident CHD. 25-Hydroxy-Vitamin-D was also added to the Framingham Risk Score (FRS) and Net-Reclassification-Improvement (NRI) and Integrated-Discriminant-Improvement (IDI) were used to examine improved reclassification. RESULTS: During follow-up, 176 events were recorded. Patients in the lowest quartile of 25-Hydroxy-Vitamin-D experienced the most number of hard CHD events. A significant linear trend was observed in hazard ratios (HR) of incident hard CHD events in 25-Hydroxy-Vitamin-D quartiles which remained significant after multiple adjustments for conventional CHD risk-factors (HRs in full-adjusted model: 2.87 [1.76-4.70] for 1st quartile, 2.31 [1.39-3.83] for 2nd quartile and 1.87 [1.15-3.03] for 3rd quartile, compared with the highest quartile; p-for-trend<0.001). Addition of 25-Hydroxy-Vitamin-D to FRS could improve CHD risk-estimation (relative-IDI = 15%, p-value<0.001). Addition of 25-Hydroxy-Vitamin-D to FRS successfully reclassified 33% [18-49] of patients with hypertension among CHD risk groups (p-value<0.001). CONCLUSION: We observed that serum 25-Hydroxy-Vitamin-D is independently associated with future hard CHD events and improves its prediction in patients with essential hypertension. Addition of serum 25-Hydroxy-Vitamin-D to CHD risk-estimation models may have additive values.
Assuntos
Doença da Artéria Coronariana/etiologia , Hipertensão/complicações , Medição de Risco/métodos , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Hipertensão Essencial , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Incidência , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Tempo , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologiaRESUMO
AIMS: Rheumatoid Arthritis (RA) is a model of chronic inflammatory disease. In this study we evaluated the correlation of leptin and CRP in patients with RA and normal controls. MAIN METHODS: A total of 75 patients with RA and 40 healthy adults were recruited in this case-control study. RA patients were categorized into high (DAS-28 > 3.2) and low activity (DAS ≤ 3.2) group according to their DAS-28 score. KEY FINDINGS: Leptin level was significantly correlated with CRP in healthy controls (r = 0.365; p < 0.05), but this correlation was lost in RA patients (r = 0.095, p = 0.41). Patients with RA had higher serum leptin levels compared to healthy controls (P < 0.01). No difference in serum leptin level was observed between patients with high and low activity disease. Also leptin was correlated with BMI in healthy controls (r = 0.326, p = 0.037). This correlation was not present in RA patients (r = 0.039, p = 0.756). SIGNIFICANCE: We observed that the physiologic correlation between leptin and CRP and BMI and CRP was not present RA patients. This is a new study reporting the lost correlation between leptin and CRP in RA patients.
RESUMO
Heat shock proteins (HSPs) have been repeatedly implicated in the pathogenesis of rheumatoid arthritis (RA). The authors aimed to study applicability of heat shock protein 70 (HSPA1A) serum levels as a diagnostic factor and a severity indicator in patients with RA and to quantify cut-off point that predicts status of RA with highest specificity. A total of 76 patients with RA and 36 healthy adults were studied in this case-control analysis. Patients had a higher HSPA1A level than the control group (0.78 ± 0.13 vs. 0.12 ± 0.02 ng/mL, p = 0.006), irrespective of presence of absence of rheumatoid factor or anti-citrullinated cyclic peptide. Next, diagnostic accuracy of the HSPA1A in diagnosis of RA was evaluated (area under curve 0.71; p < 0.05). HSPA1A predicted status of having RA in levels above 0.42 ng/mL with more than 90 % specificity. In addition to diagnostic value, HSPA1A can distinguish between high disease activity (1.66 ± 0.75 ng/mL) and low (0.49 ± 0.1 ng/mL), moderate (0.52 ± 0.12 ng/mL), or remission phase (0.48 ± 0.11 ng/mL). Moreover, patients in remission still had a higher HSPA1A level compared to normal subject (0.48 ± 0.11 vs. 0.12 ± 0.02 ng/mL, p < 0.05). Our results showed that serum HSPA1A could be implemented as a specific tool to facilitate diagnosis and monitoring disease activity in patients with rheumatoid arthritis.
Assuntos
Artrite Reumatoide/sangue , Proteínas de Choque Térmico HSP70/sangue , Adulto , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
We aimed to study whether pulse pressure (PP) predicts the response of diabetic nephropathy to glucose-lowering treatment. Patients with uncontrolled type 2 diabetes were followed for decrease in albuminuria after insulin/oral-hypoglycemic treatment. A total of 143 patients were followed for a median time of 10.5 months in a cohort study. Fasting blood sugar and HbA1C significantly decreased, while systolic, diastolic and pulse pressures remained constant during intervention. Median albuminuria decreased from 18.4 mg/day [10-40] to 16.4 mg/day [9-28] at the end of study (p-value < 0.005). The number of patients with normo/micro/macro-albuminuria changed from 98/36/9 to 108/31/4 (p-value < 0.001). No significant difference in baseline PP (47.5 ± 1.61 vs. 45.9 ± 1.81 mmHg; p-value = 0.51) or final PP (47.0 ± 2.41 vs. 49.4 ± 2.38 mmHg; p-value = 0.47) existed between those with decreased and increased albuminuria. PP was not a significant predictor of albuminuria changes in receiver operating characteristic curve (p-value = 0.77) and regression (p-value = 0.98) analyses. Benefits of glycemic control in diabetic nephropathy are independent of PP.
Assuntos
Glicemia/efeitos dos fármacos , Pressão Sanguínea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/fisiopatologia , Hipoglicemiantes/uso terapêutico , Albuminúria/etiologia , Albuminúria/fisiopatologia , Área Sob a Curva , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: Magnesium is a cofactor for numerous metabolic enzymatic reactions. It is required for glucose utilization and insulin signaling. We compared plasma magnesium concentrations in pregnant women with and without abdominal obesity, and investigated the interactive roles of magnesium and obesity in the development of gestational diabetes mellitus (GDM). METHODS: Pregnant women with and without abdominal obesity (n = 40 in each group) were followed during gestation. Oral glucose tolerance tests (OGTT) were performed at 24-28 weeks of pregnancy to diagnose GDM. Plasma glucose, insulin, triglycerides, high-sensitive C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured. The obesity-GDM relationship was investigated prospectively, and the magnesium-GDM relationship was analyzed on a cross-sectional basis. RESULTS: Sixteen patients in the obese group and one in the control developed GDM. There were no differences in plasma magnesium levels between obese and control groups (p-value = 0.14), but significant differences between diabetic and non-diabetic patients (p-value = 0.05). Fourteen out of 17 diabetic patients had magnesium concentrations below the median. Increases in insulin, homeostatic model for insulin resistance, triglycerides, hs-CRP, MDA and second-hour blood glucose were more pronounced in those with both abdominal obesity and low-normal magnesium concentrations. In the Poisson regression model, obesity (relative risk = 20.6, p-value = 0.002), low-normal magnesium level (relative risk = 4.2, p-value = 0.009), and their interaction (p-value<0.001) were significant. CONCLUSION: Abdominally obese patients with lower plasma magnesium are more likely to show abnormal OGTT results. Insulin resistance, inflammatory response and oxidative stress are exaggerated in these patients.
Assuntos
Glicemia/metabolismo , Diabetes Gestacional/etiologia , Magnésio/sangue , Obesidade Abdominal/complicações , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos Transversais , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Feminino , Teste de Tolerância a Glucose , Humanos , Mediadores da Inflamação/sangue , Insulina/sangue , Resistência à Insulina , Malondialdeído/sangue , Obesidade Abdominal/sangue , Obesidade Abdominal/diagnóstico , Estresse Oxidativo , Gravidez , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangueRESUMO
Here, we aimed to study serum heat shock protein (HSP) 70 levels in diabetic patients with and without albuminuria. We performed a 1:1 matched case control study on 40 diabetic patients with albuminuria as cases and 40 age, sex, body mass index matched diabetic patients without albuminuria (normoalbuminuria) as controls. Normoalbuminuria was defined as urinary albumin excretion rate <15 mg/12 h, and albuminuria was defined as urinary albumin excretion rate between 100-400 mg/12 h. Patients with albuminuria had a higher HSP70 than controls (0.83 ± 0.50 vs. 0.63 ± 0.06; p = 0.02), while they did not differ in any other studied variables. In ten of the studied pairs, the controls had higher HSP70 levels than cases (reverse relationship). Patients in the "direct relationship group" had higher HbA1c values than the patients in the "reverse relationship group" (8.9 ± 0.3 vs. 7.3 ± 0.6, p = 0.04). Cases in the reverse pairs had a lower low density lipoprotein cholesterol levels than their controls. The odds ratio of HSP70 in the prediction of albuminuria was (28.69 (3.2-250.1), p = 0.002). In conclusion, we have shown an increased HSP70 levels in diabetic patients with albuminuria.
Assuntos
Albuminúria/complicações , Proteínas de Choque Térmico HSP70/metabolismo , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Razão de ChancesRESUMO
In vitro and in vivo studies have shown conflicting results regarding heat shock protein (HSP) and leptin correlation. More importantly both HSP70 and leptin are correlated with C reactive proteins. The purpose of the present study was to study the correlation between serum HSP70 and leptin levels in patients with type 2 diabetes stratified according to gender. We performed a cross sectional study on the established groups of patients with type 2 diabetes defined as 1: patients with long standing diabetes for more than 3 years; and 2: patients with newly diagnosed diabetes within recent 6 months who were not on any glucose lowering treatment other than by dietary means alone and 3: healthy controls. Patients with long standing diabetes had higher HSP70, HbA1c and triglyceride than controls. Serum leptin levels were significantly lower in patients with newly diagnosed diabetes. Women with type 2 diabetes had higher leptin levels compared to men, both before and after treatment. We showed a positive correlation between leptin and HSP70 levels in women with type 2 diabetes. The correlation was strongest in women with newly diagnosed diabetes (r = 0.59) and was attenuated in women who were on treatment (r = 0.3). The significance of this correlation was only observed in women with type 2 diabetes. There was no correlation between leptin and HSP70 in men. The positive correlation between leptin and HSP is observed in chronic inflammation such as type 2 diabetes. It could be hypothesized that the observed correlation between serum HSP70 and leptin implies a higher state of chronic inflammation.