Galectin-3 inhibition prevents adipose tissue remodelling in obesity.

Extracellular matrix remodelling of the adipose tissue has a pivotal role in the pathophysiology of obesity. Galectin-3 (Gal-3) is increased in obesity and mediates inflammation and fibrosis in the cardiovascular system. However, the effects of Gal-3 on adipose tissue remodelling associated with obesity remain unclear. Male Wistar rats were fed either a high-fat diet (33.5% fat) or a standard diet (3.5% fat) for 6 weeks. Half of the animals of each group were treated with the pharmacological inhibitor of Gal-3, modified citrus pectin (MCP; 100 mg kg(-1) per day) in the drinking water. In adipose tissue, obese animals presented an increase in Gal-3 levels that were accompanied by an increase in pericellular collagen. Obese rats exhibited higher adipose tissue inflammation, as well as enhanced differentiation degree of the adipocytes. Treatment with MCP prevented all the above effects. In mature 3T3-L1 adipocytes, Gal-3 (10(-8 )m) treatment increased fibrosis, inflammatory and differentiation markers. In conclusion, Gal-3 emerges as a potential therapeutic target in adipose tissue remodelling associated with obesity and could have an important role in the development of metabolic alterations associated with obesity.

The potential role of leptin in the vascular remodeling associated with obesity.

BACKGROUND/OBJECTIVES: Extracellular matrix (ECM) participates in the vascular remodeling associated with obesity. We investigated the effects of leptin on the production of ECM components in primary cultured vascular smooth muscle cells (VSMCs) and whether leptin could be a mediator of obesity-induced vascular remodeling. METHODS: T he effects of leptin (100 ng ml(-1)) on ECM components and superoxide anion production (O(2)(.-)) were evaluated in presence or absence of the antioxidant melatonin (10(-)(3) mmol l(-1)) or the inhibitor of phosphatidylinositol 3'-kinase (PI3K), LY294002 (2 × 10(-)(4) mmol l(-1)) in VSMCs from adult rats in order to explore the role of both oxidative stress and the participation of PI3K/Akt pathway in the effects of leptin. ECM components and O(2)(.-) were quantified in the aortic media of male Wistar rats fed a high-fat diet (HFD; 33.5% fat), or a standard diet (CT; 3.5% fat) for 6 weeks. RESULTS: In VSMCs, leptin enhanced gene and protein levels of collagen I, fibronectin, transforming growth factor (TGF)-ß and connective tissue growth factor (CTGF) but did not change those of collagen III and galectin-3. Leptin also increased O(2)(.-) and Akt phosphorylation in VSMCs. These effects were prevented by the presence of either melatonin or LY294002, except O(2)(.-) production in the case of PI3K inhibition. The increase in body weight in HFD rats was accompanied by aorta thickening due to an increase in media area. The aortic fibrosis observed in HFD rats was associated with high levels of leptin, collagen type I, fibronectin, TGF-ß, CTGF, phosphorylated Akt and O(2)(.-). Aortic leptin levels were positively correlated with total collagen, collagen I, TGF-ß and CTGF levels. No differences were observed in the levels of collagen III, elastin or galectin-3 between both the groups. CONCLUSIONS: Leptin could participate in the vascular remodeling and stiffness associated with obesity by ECM production in VSMCs through the activation of oxidative stress-PI3K/Akt pathway and the production of the profibrotic factors TGF-ß and CTGF.

Benefit of combination therapy with dapagliflozin and eplerenone on cardiac function and fibrosis in rats with non-diabetic chronic kidney disease.

Patients with chronic kidney disease (CKD) are at a high risk of cardiovascular (CV) complications. In these patients, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce CV events. Mineralocorticoid receptor antagonists (MRAs) exert similar benefits in diabetic CKD, though their effects in non-diabetic CKD remain unclear. This study aimed to evaluated whether the combination of Dapagliflozin (DAPA) and Eplerenone (EPLE) would have positive effects on cardiorenal functions in a non-diabetic CKD model. CKD was induced in rats via 5/6 nephrectomy, followed by treatment with DAPA (5 mg/kg/day PO), EPLE (100 mg/kg/day PO) or the combination for 3 months following CKD induction. Cardiorenal functions were assessed after the treatment period. All treated groups showed reduced kidney fibrosis though plasma creatinine and urea levels remained unchanged. Compared to untreated CKD, EPLE or DAPA/EPLE reduced left ventricle (LV) end-diastolic pressure and LV end-diastolic pressure volume relationship, whereas DAPA alone did not achieve significant reductions. Compared to untreated CKD, EPLE and DAPA/EPLE improved cardiac perfusion but DAPA alone did not. Cardiac fibrosis in CKD was blunted by either DAPA or EPLE alone, with the combination showing an additive effect. In conclusion, co-treatment with DAPA and EPLE enhances diastolic function, cardiac perfusion and reduces myocardial fibrosis in non-diabetic CKD rats.

Galectin-3 as a novel biotarget in cardiovascular alterations associated to development of severe aortic stenosis.

Aortic stenosis is one of the most common heart valve diseases, as well as one of the most common causes of heart failure in the elderly. Currently, there are no medical therapies to prevent or slow the progression of the disease. When symptoms develop alongside severe aortic stenosis, there is a poor prognosis unless aortic valve replacement is performed. Aortic stenosis is a heterogeneous disease with a complex pathophysiology involving structural and biological changes of the valve, as well as adaptive and maladaptive compensatory changes in the myocardium and vasculature in response to chronic pressure overload. Galectin-3 serves important functions in numerous biological activities including cell growth, apoptosis, differentiation, inflammation and fibrosis. With evidence emerging to support the function of Galectin-3, the current review aims to summarize the latest literature regarding the potential of Galectin-3 as therapeutic target in aortic valve and cardiovascular alterations associated with aortic stenosis.

[A campaign for detection of beta-thalassemia minor and prevention of beta-thalassemia major in the island of Minorca. 2 years' experience]. / Campaña para la detección de la betatalasemia minor y prevención de la major en la isla de Menorca. Experiencia de dos años.

The high prevalence of beta-thalassemia minor and the occurrence of thalassemia major in Minorca prompted us to develop a prevention campaign. The selected population consisted of primary school students. The campaign was operative during the terms 1986-87 and 1987-88 and had three stages: 1.) informative; 2.) analytical study and diagnosis of carriers; 3.) report of the results and genetic counselling. We studied overall 1862 schoolchildren. The prevalence of beta-thalassemia minor was 3.38%. We discuss the methodology, the results and the effectiveness of the campaign.