Soluble TWEAK and atheromatosis progression in patients with chronic kidney disease

BACKGROUND AND AIMS: Circulating soluble TNF-like weak inducer of apoptosis (sTWEAK) concentrations are related to the presence of chronic kidney disease (CKD) and cardiovascular disease (CVD). However, there are no data regarding the potential association between sTWEAK and atheromatosis progression in patients free of cardiovascular events. METHODS: Soluble TWEAK serum concentration was measured in 702 CKD patients without any previous CV event from The National Observatory of Atherosclerosis in Nephrology (NEFRONA) Study. B-mode ultrasound was performed to detect the presence of carotid and/or femoral atherosclerotic plaques. The association between sTWEAK levels, atherosclerotic burden (number of plaques) and atheromatosis progression (increase in the number of plaques) after 24 months of follow-up was analyzed. RESULTS: A continuous decrease in sTWEAK concentrations, with an increase in the number of atherosclerotic plaques after 24 months of follow-up, was observed in the studied population. Multivariable linear regression analysis showed that age, blood pressure, HDL-c, and sTWEAK concentrations were independent predictors of atherosclerotic burden after 24 months of follow-up. In addition, sTWEAK concentrations diminished in CKD patients in whom progressive silent atherosclerosis was observed. Multivariable linear regression analysis showed that age, sex, smoking status and sTWEAK levels were independent predictors of atheromatosis progression after 24 months of follow-up. CONCLUSIONS: Lower sTWEAK concentrations are associated with atherosclerotic burden and atheromatosis progression in CKD patients free of clinical CVD. These data suggest that sTWEAK could serve as a biomarker to predict CV risk before clinical manifestations

Deficiency of MMP17/MT4-MMP proteolytic activity predisposes to aortic aneurysm in mice

Aortic dissection or rupture resulting from aneurysm causes 1% to 2% of deaths in developed countries. These disorders are associated with mutations in genes that affect vascular smooth muscle cell differentiation and contractility or extracellular matrix composition and assembly. However, as many as 75% of patients with a family history of aortic aneurysms do not have an identified genetic syndrome.Plan Nacional I+D11.551 JCR (2015) Q1, 4/124 Cardiac & cardiovascular systems, 3/70 Hematology, 2/63 Peripheral vascular diseaseUE

Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome

Heritable thoracic aortic aneurysms and dissections (TAAD), including Marfan syndrome (MFS), currently lack a cure, and causative mutations have been identified for only a fraction of affected families. Here we identify the metalloproteinase ADAMTS1 and inducible nitric oxide synthase (NOS2) as therapeutic targets in individuals with TAAD. We show that Adamts1 is a major mediator of vascular homeostasis, given that genetic haploinsufficiency of Adamts1 in mice causes TAAD similar to MFS. Aortic nitric oxide and Nos2 levels were higher in Adamts1-deficient mice and in a mouse model of MFS (hereafter referred to as MFS mice), and Nos2 inactivation protected both types of mice from aortic pathology. Pharmacological inhibition of Nos2 rapidly reversed aortic dilation and medial degeneration in young Adamts1-deficient mice and in young or old MFS mice. Patients with MFS showed elevated NOS2 and decreased ADAMTS1 protein levels in the aorta. These findings uncover a possible causative role for the ADAMTS1 NOS2 axis in human TAAD and warrant evaluation of NOS2 inhibitors for therapy

Oleoresins from Capsicum spp.: Extraction Methods and Bioactivity

Capsicum spp. fruit is one of the most produced vegetables around the world, and it is consumed both as fresh vegetable and as a spice like a food additive for their characteristic red color and, in many cases, its pungency. In addition to its economic importance, the bioactivity of some important compounds such as capsaicinoids and carotenoids has promoted its research. The use of Capsicum oleoresins has been increased due to its advantages comparing with the traditional dry spice. These include obtaining higher quality products with the desired content of bioactive and flavored substances. The wide diversity of extraction methods including water extraction, organic solvent extraction, microwave-assisted extraction, and ultrasound assisted extraction as well as supercritical fluid extraction among others are discussed in the present review. Moreover, pretreatments such as chemical treatments, osmotic dehydration, sun and oven drying, and freeze-drying commonly used before the extraction are also presented. Due to its importance, Capsicum oleoresins produced with “green” solvents and the improvement of fractional extraction techniques that allow to obtain separately the various bioactive fractions will continue under research for further development