Cardiac-Specific Overexpression of ERRγ in Mice Induces Severe Heart Dysfunction and Early Lethality

Disfunció cardíaca; Receptors relacionats amb estrògens; Ratolins transgènicsDisfunción cardíaca; Receptores relacionados con el estrógeno; Ratones transgénicosCardiac dysfunction; Estrogen-related receptors; Transgenic miceProper cardiac function depends on the coordinated expression of multiple gene networks related to fuel utilization and mitochondrial ATP production, heart contraction, and ion transport. Key transcriptional regulators that regulate these gene networks have been identified. Among them, estrogen-related receptors (ERRs) have emerged as crucial modulators of cardiac function by regulating cellular metabolism and contraction machinery. Consistent with this role, lack of ERRα or ERRγ results in cardiac derangements that lead to functional maladaptation in response to increased workload. Interestingly, metabolic inflexibility associated with diabetic cardiomyopathy has been recently associated with increased mitochondrial fatty acid oxidation and expression of ERRγ, suggesting that sustained expression of this nuclear receptor could result in a cardiac pathogenic outcome. Here, we describe the generation of mice with cardiac-specific overexpression of ERRγ, which die at young ages due to heart failure. ERRγ transgenic mice show signs of dilated cardiomyopathy associated with cardiomyocyte hypertrophy, increased cell death, and fibrosis. Our results suggest that ERRγ could play a role in mediating cardiac pathogenic responses.Research was funded by “Fundació la Marató de TV3” (# 082610 to JAV) and by Instituto de Salud Carlos III (PI19/00167 to MZ, co-funded by European Regional Development Fund -FEDER- “A way to make Europe”)

The dynamic behaviour of metabolic syndrome and its components in an eight-year population-based cohort from the Mediterranean

Síndrome X de resistència a la insulina; Síndrome metabòlica; ObesitatSíndrome X de resistencia a la insulina; Síndrome metabólico; ObesidadInsulin Resistance Syndrome X; Metabolic syndrome; ObesityBACKGROUND The significant rise in the prevalence of obesity coincides with the considerable increase in the prevalence of metabolic syndrome (MS) currently being observed worldwide. The components of MS are not static and their dynamics, such as the order of their occurrence, or the time of exposure to them are, as yet, unknown but could well be clinically relevant. Our objective was to study the dynamic behaviour of MS and its components in a large population-based cohort from a Mediterranean region. METHODS AND FINDINGS Our study employed a retrospective cohort (between January 1, 2005 and December 31, 2012) made up of individuals from the general population in a region in the northeast of Catalonia, Spain. Given that most of the explicative variables of the risk of having MS were time dependent and, therefore, the risk was not proportional, we used the Andersen-Gill (AG) model to perform a multivariate survival analysis and inferences were performed using a Bayesian framework. Thirty-nine percent of the participants developed MS; 44.6% of them with a single limited episode. Triglycerides and low HDL cholesterol, together with obesity, are components associated with the first occurrence of MS. Components related to the metabolism of glucose are associated with a medium risk of having a first episode of MS, and those related to blood pressure are associated with a lower risk. When the components related to blood pressure and the metabolism of glucose appear first, they determine the appearance of the first episode of MS. The variables concerning the persistence of MS are those that correspond to clinical conditions that do not have well-established drug treatment criteria. CONCLUSIONS Our results suggest that the components related to the metabolism of glucose and to high blood pressure appear early on and act as biomarkers for predicting MS, while the components related to obesity and dyslipidaemia, although essential for the development of MS, appear later. Making lifestyle changes reduces the conditions associated with the persistence of MS

Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area

Background: Kidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM). Methods: Cross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke). Variables of renal function were defined as follows: 1) Microalbuminuria: albumin excretion rate & 30 mg/g or 3.5 mg/mmol, 2) Macroalbuminuria: albumin excretion rate & 300 mg/g or 35 mg/mmol, 3) Kidney disease (KD): glomerular filtration rate according to Modification of Diet in Renal Disease < 60 ml/min/1.73 m2 and/or the presence of albuminuria, 4) Renal impairment (RI): glomerular filtration rate < 60 ml/min/1.73 m2, 5) Nonalbuminuric RI: glomerular filtration rate < 60 ml/min/1.73 m2 without albuminuria and, 5) Diabetic nephropathy (DN): macroalbuminuria or microalbuminuria plus diabetic retinopathy. Results: The prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN). The prevalence of albuminuria without RI (13.5%) and nonalbuminuric RI (14.7%) was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20; CI 95% 1.86-2.59), microvascular disease (OR 2.14; CI 95% 1.8-2.54) and insulin treatment (OR 1.82; CI 95% 1.39-2.38), and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80-0.91). Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21-0.35), duration of diabetes (OR 0.94 per year; CI 95% 0.91-0.97) and directly associated with HbA1c (OR 1.19 for every 1% increase; CI 95% 1.09-1.3). Conclusions: One-third of the sample population in this study has KD. The presence or absence of albuminuria identifies two subgroups with different characteristics related to gender, the duration of diabetes and metabolic status of the patient. It is important to determine both albuminuria and GFR estimation to diagnose KD

The dynamic behaviour of metabolic syndrome and its components in an eight-year population-based cohort from the Mediterranean

Síndrome X de resistència a la insulina; Síndrome metabòlica; ObesitatSíndrome X de resistencia a la insulina; Síndrome metabólico; ObesidadInsulin Resistance Syndrome X; Metabolic syndrome; ObesityBACKGROUND The significant rise in the prevalence of obesity coincides with the considerable increase in the prevalence of metabolic syndrome (MS) currently being observed worldwide. The components of MS are not static and their dynamics, such as the order of their occurrence, or the time of exposure to them are, as yet, unknown but could well be clinically relevant. Our objective was to study the dynamic behaviour of MS and its components in a large population-based cohort from a Mediterranean region. METHODS AND FINDINGS Our study employed a retrospective cohort (between January 1, 2005 and December 31, 2012) made up of individuals from the general population in a region in the northeast of Catalonia, Spain. Given that most of the explicative variables of the risk of having MS were time dependent and, therefore, the risk was not proportional, we used the Andersen-Gill (AG) model to perform a multivariate survival analysis and inferences were performed using a Bayesian framework. Thirty-nine percent of the participants developed MS; 44.6% of them with a single limited episode. Triglycerides and low HDL cholesterol, together with obesity, are components associated with the first occurrence of MS. Components related to the metabolism of glucose are associated with a medium risk of having a first episode of MS, and those related to blood pressure are associated with a lower risk. When the components related to blood pressure and the metabolism of glucose appear first, they determine the appearance of the first episode of MS. The variables concerning the persistence of MS are those that correspond to clinical conditions that do not have well-established drug treatment criteria. CONCLUSIONS Our results suggest that the components related to the metabolism of glucose and to high blood pressure appear early on and act as biomarkers for predicting MS, while the components related to obesity and dyslipidaemia, although essential for the development of MS, appear later. Making lifestyle changes reduces the conditions associated with the persistence of MS