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1.
Nutr Metab Cardiovasc Dis ; 34(8): 1874-1878, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38664124

RESUMEN

BACKGROUND AND AIMS: While serum osteopontin (OPN)'s established role in cardiometabolic risk is recognized, its potential as a predictor of metabolic syndrome (MetS) improvement through a urine assay has not yet been demonstrated. In this study, we propose its potential predictive role over a 12-month period of standard care, with the ability to complement anthropometric measures. METHODS AND RESULTS: Hierarchical clustering revealed a notable association of urinary OPN (uOPN) with MetS criteria and overcame anthropometric measures in predicting the improvement at 12 months (OR of 2.74 [95% CI 1.32 to 6.29]). uOPN significantly contributed to the homogeneity of the nodes in the random forest and ultimately enhanced the performance of anthropometric measures when assessed for accuracy and area under the curve (AUC). CONCLUSION: Our findings offer insights into potential applications in cardiometabolic medicine for uOPN, which is easily detectable in non-invasive biological samples through an affordable assay.


Asunto(s)
Biomarcadores , Síndrome Metabólico , Osteopontina , Valor Predictivo de las Pruebas , Urinálisis , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/orina , Síndrome Metabólico/sangre , Humanos , Osteopontina/orina , Osteopontina/sangre , Masculino , Femenino , Biomarcadores/orina , Biomarcadores/sangre , Persona de Mediana Edad , Factores de Tiempo , Adulto , Resultado del Tratamiento , Anciano , Factores de Riesgo Cardiometabólico
2.
Nutr Metab Cardiovasc Dis ; 33(1): 185-193, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36411219

RESUMEN

BACKGROUND AND AIMS: Inflammation due to the excess of nutrient intake plays an important role in the pathophysiology of metabolic syndrome (MetS). Here, the potential influence of neutrophils and their degranulation markers on MetS improvement upon dietary and behavioral counselling, has been investigated. Specifically, we aimed at investigating their role as potential predictors of metabolic syndrome improvements. METHODS AND RESULTS: patients with MetS (n = 127) received behavioral and dietary recommendations before follow-up at 6 months. Serum levels of matrix metalloproteinases (MMP)8, MMP9, myeloperoxidase (MPO), tissue inhibitor of MMP (TIMP)-1, TIMP-2, TIMP-3 and resistin were tested at baseline. In the whole cohort, baseline levels of proinflammatory MMP8, MMP9 and MPO increased together with the number of MetS criteria. Seventy-three (57%) patients experienced a reduction in MetS-defining criteria at follow-up. With respect to those with no improvement, such individuals showed lower weight and waist circumference at enrolment, less frequent smoking habits, higher levels of triglycerides and lower circulating MMP8. At logistic regression analysis, baseline MMP8 showed negative predictive ability (odds ratio (OR) 0.979 [0.961-0.997]; p = 0.025) against MetS improvement. Such findings hold true even when included in the backward stepwise logistic regression model confirming MMP8 as an independent predictor (OR 0.970 [0.949-0.993]; p = 0.009). Receiver operating characteristic (ROC) curve confirmed the predictive ability of MMP8 combined in a model including baseline MetS criteria and waist circumference. Bootstrap resampling analysis internally validated our findings. CONCLUSION: Improvement of MetS is independently associated with baseline low MMP-8 levels, suggesting a pivotal role for inflammation in metabolic alteration.


Asunto(s)
Síndrome Metabólico , Humanos , Síndrome Metabólico/diagnóstico , Metaloproteinasa 8 de la Matriz , Metaloproteinasa 9 de la Matriz , Neutrófilos/metabolismo , Biomarcadores , Inflamación , Curva ROC , Circunferencia de la Cintura
3.
Eur J Clin Invest ; 51(3): e13403, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32918277

RESUMEN

Prediabetes is often observed in patients with Metabolic Syndrome (MetS) and might be associated with metabolic and inflammatory alterations. Here, we investigated whether the inflammatory molecule osteopontin (OPN) might have a prognostic impact in a cohort of MetS patients (n = 85) with baseline normal glycaemia or impaired fasting glucose (IFG) over one year of recommended pharmacological treatments and Mediterranean diet. Patients were then followed up for 12 months with intermediate evaluation after 6 months. At all time points, anthropometric and clinical data were recorded, alongside with haematological and biochemical profiles, including serum concentrations of OPN. As expected, Mediterranean diet improves glycaemic profile in patients with IFG. Baseline serum OPN failed to be associated with baseline anthropometric or biochemical variables. At baseline, higher levels of OPN were shown in patients with IFG as compared to normal glycaemia. Two distinct subgroups of patients in whom OPN decreased or remained stable/increased at follow-up were identified. When higher serum OPN levels were observed at baseline, greater reduction was observed at 1-year follow-up. Reduction in circulating OPN levels was associated with metabolic improvement in terms of blood pressure, LDL-c, HDL-c, and glycaemia. At both univariate and adjusted logistic regression analyses, serum OPN emerged as an independent predictor of glycaemic profile improvement at 1-year follow-up (adjOR 1.05 [1.00-1.10]; P = .041). In conclusion, pharmacological and dietetic interventions improved glycaemic profile in patients with MetS. In particular, glycaemic improvement was demonstrated in patients who also reduce circulating OPN levels. Higher OPN levels at baseline predict normalization of glycaemic profile.


Asunto(s)
Glucemia/metabolismo , Dieta Mediterránea , Intolerancia a la Glucosa/dietoterapia , Síndrome Metabólico/dietoterapia , Osteopontina/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Intolerancia a la Glucosa/metabolismo , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólico/metabolismo , Persona de Mediana Edad , Proyectos Piloto , Pronóstico
4.
Int J Mol Sci ; 21(19)2020 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-32977685

RESUMEN

Thrombolysis is the gold standard treatment for acute ischemic stroke. Besides its fibrinolytic role, recombinant tissue plasminogen activator (r-tPA) holds several non-fibrinolytic functions. Here, we investigated the potential role of r-tPA on human primary neutrophil migration in vitro. By means of modified Boyden chamber migration assay and checkerboard analysis we showed a dose-dependent chemotactic effect of r-TPA with a maximum effect reached by 0.03 mg/mL (0.003-1 mg/mL). Pre-incubation with MAP kinases inhibitors allowed the identification of PI3K/Akt, but not ERK1/2 as the intracellular pathway mediating the observed effects. Furthermore, by means of real-time PCR, immunocytochemistry and cytofluorimetry we demonstrated that the r-tPA receptor low density lipoprotein receptor-related protein 1 (LRP-1) is synthetized and expressed by neutrophils in response to r-tPA and TNF-α. Inhibition of LRP-1 by receptor-associated protein (RAP), prevented r-tPA-mediated F-actin polymerization, migration and signal through Akt but not ERK1/2. Lastly, also neutrophil degranulation in response to r-tPA seems to be mediated by LRP-1 under adhesion conditions. In conclusion, we show that r-tPA induces neutrophil chemotaxis through LRP-1/Akt pathway. Blunting r-tPA-mediated neutrophil activation might be beneficial as an adjuvant therapy to thrombolysis in this setting.


Asunto(s)
Quimiotaxis/efectos de los fármacos , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neutrófilos/metabolismo , Activador de Tejido Plasminógeno/farmacología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Proteínas Recombinantes/farmacología
5.
Eur J Clin Invest ; 49(8): e13128, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31091356

RESUMEN

BACKGROUND: Inflammation, overweight and other cardiovascular risk factors might negatively impact on hypertension remission in metabolic syndrome (MetS), independently of the pharmacological treatment. Here, the potential influence of systemic inflammation (assessed by serum high-sensitivity C-reactive protein [hs-CRP]) on hypertension remission will be investigated in a cohort of hypertensive patients with MetS. MATERIAL AND METHODS: Hypertensive patients with MetS (n = 100) were enrolled, treated under current behavior/dietary/pharmacological recommendations and followed up for 12 months. All patients received medications and nutritional advice based on Mediterranean-like dietary pattern in addition to psychological and physical activity counselling. At baseline (T0), 6 (T1) and 12 (T2) months of follow-up, clinical data, haematological and biochemical profiles and serum hs-CRP were measured. RESULTS: As compared to T0, at T2 patients displayed improvements in anthropometric and metabolic profiles. At T2, the hypertension remission rate was 13.0%. Serum hs-CRP did not change overtime in the overall cohort. Surprisingly, patients who experienced hypertension remission were less treated with antihypertensive drugs, but developed a weak improvement in anthropometric measures during follow-up. The hypertension remission group had lower baseline levels of hs-CRP as compared to non-remission. Low baseline hs-CRP (<2 µg/mL, cut-off value identified by ROC curve) predicted hypertension remission, independently of antihypertensive treatment implementation, baseline systolic blood pressure and waist circumference improvement. CONCLUSIONS: Remission of hypertension in MetS is independently associated with baseline low CRP levels, which might suggest a critical role for inflammation in sustaining high blood pressure levels.


Asunto(s)
Proteína C-Reactiva/metabolismo , Hipertensión/sangre , Síndrome Metabólico/sangre , Adulto , Antropometría , Antihipertensivos/uso terapéutico , Estudios de Cohortes , Dieta , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/dietoterapia , Hipertensión/tratamiento farmacológico , Inflamación/dietoterapia , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/dietoterapia , Síndrome Metabólico/tratamiento farmacológico , Metaboloma , Persona de Mediana Edad , Sobrepeso/complicaciones , Curva ROC , Remisión Espontánea , Circunferencia de la Cintura , Adulto Joven
6.
Eur J Clin Invest ; 48(3)2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29327345

RESUMEN

BACKGROUND: Different cut-off values of serum lipoprotein (a) [Lp (a)] were recently identified to better stratify cardiovascular risk categories. Both pathophysiological and prognostic values of Lp (a) remain unclear. MATERIALS AND METHODS: Here, the prognostic value of Lp (a) and its correlation with intraplaque features were assessed in patients with severe carotid artery stenosis undergoing endarterectomy (n = 180). The cut-off value of 10 mg/dL for serum Lp (a) was selected to predict 24-month follow-up acute coronary syndrome (ACS). In addition, the association between serum Lp (a) and intraplaque lipids, collagen, inflammatory and vascular cells was assessed. Serum Lp (a) levels were measured by nephelometric assay. RESULTS: Patients with high Lp (a) had similar comorbidities, medications and laboratory parameters as compared to low Lp (a) levels. At 24-month follow-up, patients with high Lp (a) had more ACS as compared to low levels. Histological parameters within plaques were comparable in the study groups. No significant correlation between Lp (a) serum levels and intraplaque parameters was found, except for a weak positive association with smooth muscle cells in upstream plaque portions. When adjusted for gender, the presence of dyslipidaemia and chronic coronary artery disease, Lp (a) ≥10 mg/dL remained predictive for ACS. CONCLUSIONS: Lp (a) determination could be a useful tool to predict ACS in patients with severe carotid stenosis.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Estenosis Carotídea/complicaciones , Lipoproteína(a)/metabolismo , Síndrome Coronario Agudo/sangre , Cuidados Posteriores , Anciano , Biomarcadores/metabolismo , Estenosis Carotídea/sangre , Femenino , Humanos , Masculino , Proyectos Piloto , Placa Aterosclerótica/sangre , Placa Aterosclerótica/diagnóstico
9.
Eur J Clin Invest ; 46(3): 252-63, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26573245

RESUMEN

BACKGROUND: The role of neutrophils in the beginning and the progression of the atherosclerotic process did not receive much attention until the last years. On the contrary, recent data, in both the experimental animals and humans, suggest important effects of these cells with possible clinical consequences. MATERIALS AND METHODS: This narrative review was based on the papers found on PubMed and MEDLINE up to July 2015. The search terms used were 'neutrophil, atherosclerosis' in combination with 'recruitment, chemokine, plaque destabilization and pathophysiology'. RESULTS: Different models demonstrate the presence and the actions of neutrophils in the early steps of the atherogenesis confirming the fundamental role of these cells in the response of the innate immune system to different pathogens (in this context the modified lipoproteins). However, also the late phases of the atherosclerotic process, in particular the destabilization of a mature plaque, seem to be modulated by the neutrophils, possibly through the interaction with recently discovered biological systems such as the endocannabinoids. CONCLUSIONS: The understanding of the mechanisms involved in the modulation exerted by neutrophils in atherosclerosis is pivotal in terms of the complete definition of the overall picture. This approach will certainly give us new targets and new pharmacological opportunities for the anti-inflammatory strategy of the cardiovascular prevention.


Asunto(s)
Aterosclerosis/inmunología , Infiltración Neutrófila/inmunología , Neutrófilos/inmunología , Placa Aterosclerótica/inmunología , Animales , Aterosclerosis/fisiopatología , Quimiocinas/inmunología , Progresión de la Enfermedad , Endocannabinoides/inmunología , Humanos , Inmunidad Innata/inmunología , Neutrófilos/citología , Placa Aterosclerótica/fisiopatología
10.
Mediators Inflamm ; 2016: 9153673, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27738391

RESUMEN

Serum c-reactive protein (CRP) was suggested for the assessment of intermediate cardiovascular (CV) risk. Here, systemic or intraplaque CRP levels were investigated as predictors of major adverse cardiovascular events (MACEs) in patients with severe carotid stenosis. CRP levels were assessed in the serum and within different portions (upstream and downstream) of carotid plaques of 217 patients undergoing endarterectomy. The association between CRP and intraplaque lipids, collagen, neutrophils, smooth muscle cells (SMC), and macrophage subsets was determined. No correlation between serum CRP and intraplaque biomarkers was observed. In upstream portions, CRP content was directly correlated with intraplaque neutrophils, total macrophages, and M1 macrophages and inversely correlated with SMC content. In downstream portions, intraplaque CRP correlated with M1 and M2 macrophages. According to the cut-off point (CRP > 2.9%) identified by ROC analysis in upstream portions, Kaplan-Meier analysis showed that patients with high CRP levels had a greater rate of MACEs. This risk of MACEs increased independently of age, male gender, serum CRP, and statin use. In conclusion, in patients with severe carotid artery stenosis, high CRP levels within upstream portions of carotid plaques directly and positively correlate with intraplaque inflammatory cells and predict MACEs at an 18-month follow-up period.


Asunto(s)
Proteína C-Reactiva/metabolismo , Estenosis Carotídea/metabolismo , Factores de Edad , Anciano , Biomarcadores/sangre , Biomarcadores/metabolismo , Estenosis Carotídea/sangre , Femenino , Humanos , Estimación de Kaplan-Meier , Macrófagos/metabolismo , Masculino , Miocitos del Músculo Liso/metabolismo , Neutrófilos/metabolismo , Curva ROC , Factores de Riesgo , Factores Sexuales
11.
Clin Exp Hypertens ; 38(2): 143-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26418513

RESUMEN

The aim of this study was to evaluate the prevalence of erectile dysfunction (ED) in a cohort of Italian hypertensive men and the association with clinical and biochemical data. The study involved 270 consecutive hypertensive subjects aged 40-70 years evaluated in Italian Hypertension Centers of six hospitals from Liguria and Piedmont. ED was assessed through the self-administered questionnaire of the International Index of Erectile Function. Clinical history with ongoing drug treatment, various clinical parameters, biochemical data and evidence about the presence of subclinical target organ damage was collected. Twenty-seven subjects refused to answer the questionnaire (10%). Among the 243 remained subjects, 123 presented ED (50.6%). ED was highly related to age, systolic blood pressure, pulse pressure, smoking status, statin therapy and kidney function. The addition of a thiazide diuretic to an inhibitor of the renin-angiotensin system significantly increased the prevalence of ED. The prevalence of ED increased in relation with the number of hypotensive drug classes taken by the patients. ED was highly prevalent in this cohort of Italian hypertensive subjects and was associated with other cardiovascular risk factors, such as age, smoking status and kidney function. The role of ED as an early marker of cardiovascular disease is discussed.


Asunto(s)
Dislipidemias/epidemiología , Disfunción Eréctil/epidemiología , Hipertensión/epidemiología , Insuficiencia Renal/epidemiología , Fumar/epidemiología , Adulto , Factores de Edad , Anciano , Albuminuria/epidemiología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea , Enfermedades Cardiovasculares/epidemiología , Creatinina/sangre , Dislipidemias/tratamiento farmacológico , Tasa de Filtración Glomerular , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/epidemiología , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal/sangre , Factores de Riesgo , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Encuestas y Cuestionarios , Ultrasonografía
12.
Eur J Clin Invest ; 44(11): 1122-34, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25231921

RESUMEN

BACKGROUND: Both pathophysiology and treatments of carotid atherosclerotic plaque stenosis represent two interesting fields of strong scientific investigation. Among different drugs, safety and efficacy of statin treatment have been widely investigated and proved. MATERIALS AND METHODS: This narrative review is based on the material searched for and obtained via MEDLINE and PubMed up to March 2014. The search terms we used were: 'carotid plaque, intima-media thickness, plaque burden, stroke' in combination with 'statins, pleiotropic effects, HMG-CoA reductase inhibitors, lipid-lowering drugs'. RESULTS: Carotid stenosis represents both a useful parameter to evaluate the atherosclerotic burden and a target for therapeutic (medical or surgical) decisions. Statins do not only improve the lipid profile, but also induce some 'pleiotropic' anti-inflammatory activities that contribute to carotid plaque stabilization. Statin-mediated protective activities are under active investigation at subclinical levels with the potential benefit of advanced imaging techniques. However, considering that some new techniques (excepted B-mode ultrasound) remain quite expensive, they can have for the moment an important role in research, but not in the clinical field. CONCLUSIONS: Emerging evidence suggests that statin treatment improves carotid atherosclerosis, inducing a partial regression of plaque inflammation and size. Innovative imaging techniques might also ameliorate the identification of patients at high risk of cerebrovascular and coronary events, for which preventive statin treatments might be essential.


Asunto(s)
Estenosis Carotídea/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Placa Aterosclerótica/tratamiento farmacológico , Grosor Intima-Media Carotídeo , Estenosis Carotídea/diagnóstico , Estenosis Carotídea/etiología , Enfermedad de la Arteria Coronaria/prevención & control , Humanos , Imagen por Resonancia Magnética , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Tomografía Computarizada de Emisión de Fotón Único
13.
Eur J Clin Invest ; 44(2): 219-30, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24289238

RESUMEN

BACKGROUND: It is well known that inappropriate or exaggerated activity of the renin-angiotensin system might contribute to the development of systemic hypertension with consequent organ injury and associated increased risk of acute cardiovascular (CV) diseases. This review will discuss evidence form basic research and clinical studies, investigating the efficacy of angiotensin II receptor blockers (ARBs) in the management of acute coronary syndromes (ACS). MATERIALS AND METHODS: This narrative review is based on the material found on MEDLINE and PubMed up to June 2013. We looked for the terms 'angiotensin, AT1 receptor, ACE inhibitors' in combination with 'acute coronary syndromes, acute myocardial infarction, pathophysiology'. RESULTS: Preclinical studies showed relevant protective effects of ARBs to reduce adverse cardiac remodelling in animal models of acute cardiac ischaemia. However, although recommended in Consensus guidelines as a good alternative to angiotensin-converting enzyme inhibitors (ACEIs), clinical studies did not confirm a superior efficacy of the ARBs as compared to ACEIs. As a matter of fact for some authors, these drugs might potentially have deleterious effects increasing the CV risk. CONCLUSIONS: Emerging evidence from clinical trials suggests that the use of ARBs in ACS might be controversial, and caution should be used for their clinical use to replace ACEIs in ACS.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Enzima Convertidora de Angiotensina 2 , Ensayos Clínicos como Asunto , Humanos , Peptidil-Dipeptidasa A/biosíntesis , Receptor de Angiotensina Tipo 2/fisiología , Receptores Acoplados a Proteínas G/fisiología , Factores de Riesgo , Remodelación Vascular/fisiología
14.
Mediators Inflamm ; 2014: 720987, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24648660

RESUMEN

Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN), RANKL/osteoprotegerin (OPG) ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content) as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.


Asunto(s)
Estenosis Carotídea/patología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , FN-kappa B/metabolismo , Neutrófilos/citología , Ligando RANK/sangre , Anciano , Aterosclerosis/tratamiento farmacológico , Atorvastatina , Estudios de Cohortes , Femenino , Fluorobencenos/uso terapéutico , Ácidos Heptanoicos/uso terapéutico , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Activación Neutrófila , Neutrófilos/efectos de los fármacos , Osteopontina/metabolismo , Osteoprotegerina/metabolismo , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , ARN Mensajero/metabolismo , Factores de Riesgo , Rosuvastatina Cálcica , Simvastatina/uso terapéutico , Sulfonamidas/uso terapéutico
15.
Int J Cardiol ; 400: 131791, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38244890

RESUMEN

BACKGROUND: Adipokines are key mediators of inflammation in metabolic syndrome perpetuating the effect of excess nutrient intake by setting a self-maintaining vicious circle. Here, we assess levels of adiponectin and leptin in a cohort of individuals with MetS undergoing dietary and behavioral counselling. Specifically, we investigate their role as predictors of metabolic syndrome remission after 1 year. METHODS: Patients with MetS (n = 127) received behavioral and dietary recommendations and were followed-up for 1 year. Serum was available for 108 individuals, levels of adiponectin and leptin were tested at baseline, at 6 months (t1) and after 1 year (t2). Adiponectin/leptin (A/L) ratio was also calculated and tested for predictive ability. RESULT: At the end of the follow-up period, 59 patients did not show enough criteria to define MetS anymore. When considered alone, adiponectin and leptin levels did not show difference over follow-up. Their ratio instead was significantly reduced at t1 and t2 with respect to baseline. Remitters also showed lowers level of leptin and A/L ratio as compared to non-remitters at t1. At this timepoint, A/L ratio independently predicted MetS remission at 1 year [OR 9.082 95%CI (1.394-59.160), p = 0.021]. Bootstrap resampling analysis internally validated our findings. CONCLUSIONS: Preliminary results from our pilot study suggest that MetS remission after counselling associates with changes in adipokine balance. A/L ratio decreases overtime and its value at 6 months can independently predict MetS remission.


Asunto(s)
Leptina , Síndrome Metabólico , Humanos , Síndrome Metabólico/diagnóstico , Adiponectina , Proyectos Piloto , Adipoquinas
16.
Eur Heart J ; 33(7): 846-56, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22112961

RESUMEN

AIMS: The activation of cannabinoid receptor type 2 (CB(2))-mediated pathways might represent a promising anti-atherosclerotic treatment. Here, we investigated the expression of the endocannabinoid system in human carotid plaques and the impact of CB(2) pharmacological activation on markers of plaque vulnerability in vivo and in vitro. METHODS AND RESULTS: The study was conducted using all available residual human carotid tissues (upstream and downstream the blood flow) from our cohort of patients symptomatic (n = 13) or asymptomatic (n = 27) for ischaemic stroke. Intraplaque levels of 2-arachidonoylglycerol, anandamide N-arachidonoylethanolamine, N-palmitoylethanolamine, N-oleoylethanolamine, and their degrading enzymes (fatty acid amide hydrolase and monoacylglycerol lipase) were not different in human plaque portions. In the majority of human samples, CB(1) (both mRNA and protein levels) was undetectable. In downstream symptomatic plaques, CB(2) protein expression was reduced when compared with asymptomatic patients. In these portions, CB(2) levels were inversely correlated (r = -0.4008, P = 0.0170) with matrix metalloprotease (MMP)-9 content and positively (r = 0.3997, P = 0.0174) with collagen. In mouse plaques, CB(2) co-localized with neutrophils and MMP-9. Treatment with the selective CB(2) agonist JWH-133 was associated with the reduction in MMP-9 content in aortic root and carotid plaques. In vitro, pre-incubation with JWH-133 reduced tumour necrosis factor (TNF)-α-mediated release of MMP-9. This effect was associated with the reduction in TNF-α-induced ERK1/2 phosphorylation in human neutrophils. CONCLUSION: Cannabinoid receptor type 2 receptor is down-regulated in unstable human carotid plaques. Since CB(2) activation prevents neutrophil release of MMP-9 in vivo and in vitro, this treatment strategy might selectively reduce carotid vulnerability in humans.


Asunto(s)
Arteria Carótida Interna/metabolismo , Estenosis Carotídea/metabolismo , Metaloproteinasa 9 de la Matriz/fisiología , Placa Aterosclerótica/metabolismo , Receptor Cannabinoide CB2/metabolismo , Anciano , Animales , Aorta Torácica/metabolismo , Cannabinoides/farmacología , Estudios de Casos y Controles , Femenino , Flavonoides/farmacología , Humanos , Indoles/farmacología , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Neutrófilos/metabolismo , Fosforilación/fisiología , Inhibidores de Proteínas Quinasas/farmacología , Receptor Cannabinoide CB2/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo
17.
Hypertens Res ; 46(6): 1570-1581, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36805031

RESUMEN

Hypertensive urgencies (HU) and hypertensive emergencies (HE) are challenges for the Emergency Department (ED). A prospective multicentre study is ongoing to characterize patients with acute hypertensive disorders, prevalence of subclinical hypertension-mediated organ damage (HMOD), short- and long-term prognosis; this is a preliminary report. Patients admitted to the ED with symptomatic blood pressure (BP) ≥180/110 mmHg were enrolled. They were managed by ED personnel according to their clinical presentations. Subsequently they underwent clinical evaluation and subclinical HMOD assessment at a Hypertension Centre within 72 h from enrolment. 122 patients were included in this report. Mean age was 60.7±13.9 years, 52.5% were females. 18 (14.8%) patients were diagnosed with HE, 108 (88.5%) with HU. There were no differences in gender, BMI, and cardiovascular comorbidities between groups. At ED discharge, 66.7% and 93.6% (p = 0.003) of HE and HU patients, respectively, had BP < 180/110 mmHg. After 72 h, 34.4% of patients resulted normotensive; 35.2%, 22.1%, and 8.2% had hypertension grade 1, 2, and 3, respectively. Patients with uncontrolled BP at office evaluation had higher vascular HMOD (49.1 vs. 25.9%, p = 0.045). Cardiac (60 vs. 34%, p = 0.049), renal (27.8 vs. 9.6%, p = 0.010) and cerebral (100 vs. 21%, p < 0.001) HMOD was more frequent in HE compared to HU group. HE showed greater cardiac, renal, and cerebral subclinical HMOD, compared to HU. 72-hours BP control is not associated with different HMOD, except for vascular HMOD; therefore, proper comprehensive examination after discharge from the ED could provide added value in cardiovascular risk stratification of such patients. One third of patients with acute blood pressure rise evaluated to the ED resulted normotensive at office evaluation (<72 hours after discharge). Patients with hypertensive emergency showed greater cardiac, renal, and cerebral subclinical HMOD, compared to the patients with hypertensive urgency. BP: blood pressure; HMOD: hypertension-mediated organ damage; y.o.: years old; mo.: months.


Asunto(s)
Hipertensión Maligna , Hipertensión , Femenino , Humanos , Persona de Mediana Edad , Anciano , Masculino , Urgencias Médicas , Estudios Prospectivos , Presión Sanguínea , Italia/epidemiología
18.
Eur Heart J ; 32(4): 412-21, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21224292

RESUMEN

AIMS: Anti-Apolipoprotein A-1 auto-antibodies (anti-ApoA-1 IgG) represent an emerging prognostic cardiovascular marker in patients with myocardial infarction or autoimmune diseases associated with high cardiovascular risk. The potential relationship between anti-ApoA-1 IgG and plaque vulnerability remains elusive. Thus, we aimed to investigate the role of anti-ApoA-1 IgG in plaque vulnerability. METHODS AND RESULTS: Potential relationship between anti-ApoA-1 IgG and features of cardiovascular vulnerability was explored both in vivo and in vitro. In vivo, we investigated anti-ApoA-1 IgG in patients with severe carotid stenosis (n = 102) and in ApoE-/- mice infused with polyclonal anti-ApoA-1 IgG. In vitro, anti-ApoA-1 IgG effects were assessed on human primary macrophages, monocytes, and neutrophils. Intraplaque collagen was decreased, while neutrophil and matrix metalloprotease (MMP)-9 content were increased in anti-ApoA-1 IgG-positive patients and anti-ApoA-1 IgG-treated mice when compared with corresponding controls. In mouse aortic roots (but not in abdominal aortas), treatment with anti-ApoA-1 IgG was associated with increased lesion size when compared with controls. In humans, serum anti-ApoA-1 IgG levels positively correlated with intraplaque macrophage, neutrophil, and MMP-9 content, and inversely with collagen. In vitro, anti-ApoA-1 IgG increased macrophage release of CCL2, CXCL8, and MMP-9, as well as neutrophil migration towards TNF-α or CXCL8. CONCLUSION: These results suggest that anti-ApoA-1 IgG might be associated with increased atherosclerotic plaque vulnerability in humans and mice.


Asunto(s)
Apolipoproteína A-I/inmunología , Autoanticuerpos/sangre , Arteria Carótida Interna , Estenosis Carotídea/inmunología , Placa Aterosclerótica/inmunología , Anciano , Animales , Biomarcadores/sangre , Estudios de Cohortes , Colágeno/metabolismo , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL
19.
Front Mol Biosci ; 9: 854624, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35755826

RESUMEN

Background and Aim: High lipoprotein(a) [Lp(a)] is a well-established cardiovascular (CV) risk factor, but the effect of mildly elevated Lp(a) on CV health is largely unknown. Our aim was to evaluate if Lp(a) is associated with the severity of carotid atherosclerosis (CA) in the specific subset of metabolic syndrome (MetS). Patients and Methods: Subjects with diagnosed MetS and ultrasound-assessed CA were enrolled. Those patients were categorized according to the severity of CA (moderate vs. severe), and the circulating levels of Lp(a) alongside with clinical, anthropometric, and biochemical data were collected. Results: Sixty-five patients were finally included: twenty-five with moderate and forty with severe CA (all with asymptomatic disease). Intergroup comparison showed Lp(a) as the only significantly different variable [6 (2-12) mg/dl vs. 11.5 (6-29.5) mg/dl; p = 0.018]. Circulating levels of Lp(a) were also confirmed as the only variable independently associated with severity of CA at logistic regression analysis [OR 2.9 (95% CI 1.1-7.8); p = 0.040]. ROC curve analysis for Lp(a) confirmed a serum level of 10 mg/dl as the best cut-off value [AUC 0.675 (95% CI 0.548-0.786)]. Although sensitivity and specificity were suboptimal (69.0 and 70.4%, respectively)-likely due to the small sample size-this result is in line with those previously reported in the literature. Conclusion: Lp(a) is independently associated with severity of CA in the subgroup of MetS patients.

20.
Am J Physiol Endocrinol Metab ; 300(4): E681-90, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21266669

RESUMEN

Metabolic syndrome is a proatherosclerotic condition clustering cardiovascular risk factors, including glucose and lipid profile alterations. The pathophysiological mechanisms favoring atherosclerotic inflammation in the metabolic syndrome remain elusive. Here, we investigated the potential role of the antilipolytic drug acipimox on neutrophil- and monocyte-mediated inflammation in the metabolic syndrome. Acipimox (500 mg) was orally administered to metabolic syndrome patients (n = 11) or healthy controls (n = 8). Serum and plasma was collected before acipimox administration (time 0) as well as 2-5 h afterward to assess metabolic and hematologic parameters. In vitro, the effects of the incubation with metabolic syndrome serum were assessed on human neutrophil and monocyte migration toward the proatherosclerotic chemokine CCL3. Two to five hours after acipimox administration, a significant reduction in circulating levels of insulin and nonesterified fatty acid (NEFA) was shown in metabolic syndrome patients. At time 0 and 2 h after acipimox administration, metabolic syndrome serum increased neutrophil migration to CCL3 compared with healthy controls. No effect was shown in human monocytes. At these time points, serum-induced neutrophil migration positively correlated with serum levels of insulin and NEFA. Metabolic syndrome serum or recombinant insulin did not upregulate CCR5 expression on neutrophil surface membrane, but it increased intracellular JNK1/2 phosphorylation. Insulin immunodepletion blocked serum-induced neutrophil migration and associated JNK1/2 phosphorylation. Although mRNA expression of acipimox receptor (GPR109) was shown in human neutrophils, 5-500 µM acipimox did not affect insulin-induced neutrophil migration. In conclusion, results suggest that acipimox inhibited neutrophil proatherosclerotic functions in the metabolic syndrome through the reduction in circulating levels of insulin.


Asunto(s)
Inflamación/prevención & control , Insulina/sangre , Síndrome Metabólico/sangre , Síndrome Metabólico/tratamiento farmacológico , Pirazinas/farmacología , Administración Oral , Adulto , Algoritmos , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Hipolipemiantes/administración & dosificación , Hipolipemiantes/farmacología , Inflamación/sangre , Inflamación/complicaciones , Inflamación/inmunología , Insulina/metabolismo , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/inmunología , Persona de Mediana Edad , Neutrófilos/inmunología , Neutrófilos/fisiología , Pirazinas/administración & dosificación , Factores de Tiempo
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