Upregulation in Inflammation and Collagen Expression in Perirenal but Not in Mesenteric Adipose Tissue from Diabetic Munich Wistar Frömter Rats.

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.

Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors.

The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) in type 2 diabetes (T2D). We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. Oral treatment with FIN (10 mg/kg/day in rat chow) in diabetic animals (D-FIN) was compared to a group of D rats receiving no treatment and a group of non-diabetic untreated MWF rats (C) (n = 7-10 animals per group).

Imbalance in Bone Morphogenic Proteins 2 and 7 Is Associated with Renal and Cardiovascular Damage in Chronic Kidney Disease.

Arterial stiffness is a major vascular complication of chronic kidney disease (CKD). The development of renal damage, hypertension, and increased pulse wave velocity (PWV) in CKD might be associated with an imbalance in bone morphogenetic proteins (BMP)-2 and BMP-7. Plasma BMP-2 and BMP-7 were determined by ELISA in CKD patients (stages I-III; n = 95) and Munich Wistar Frömter (MWF) rats.

Impact of pharmacist's intervention on reducing cardiovascular risk in obese patients.

Background Obesity is a risk factor for cardiovascular disease, the leading cause of death. Health education, nutritional follow-up, and life style habits modification are key for cardiovascular risk reduction in obese patients. Objective To measure the impact of pharmacist's intervention on cardiovascular risk in obese patients.

Beneficial Effect of Bariatric Surgery on Abnormal MMP-9 and AMPK Activities: Potential Markers of Obesity-Related CV Risk.

Bariatric surgery (BS) results in sustained weight loss and may reverse inflammation, metabolic alterations, extracellular matrix remodeling and arterial stiffness. We hypothesize that increased stiffening in omental arteries from obese patients might be associated with an increase in MMP activity and a decrease in p-AMPK, together with systemic oxidative stress and inflammation. Moreover, BS could contribute to reversing these alterations.

Caloric restriction induces HO formation as a trigger of AMPK-eNOS-NO pathway in obese rats: Role for CAMKII.

Caloric restriction (CR) improves endothelial function through the upregulation of adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). Moreover, hydrogen peroxide (HO) is upregulated in yeast subjected to CR. Our aim was to assess if mild short-term CR increases vascular HO formation as a link with AMPK and eNOS activation.

Role of PVAT in coronary atherosclerosis and vein graft patency: friend or foe?

Unlabelled: Perivascular adipose tissue (PVAT) releases numerous factors and adipokines with paracrine effects on both vascular structure and function. These effects are variable as they depend on regional differences in PVAT among blood vessels and vary with changes in adiposity. There is considerable evidence demonstrating an association between coronary PVAT and the development and progression of coronary artery disease, which is associated with inflammation, oxidative stress, angiogenesis, vascular remodelling and blood clotting.

Role of matrix metalloproteinase-9 in chronic kidney disease: a new biomarker of resistant albuminuria.

Resistant albuminuria, developed under adequate chronic blockade of the renin-angiotensin system, is a clinical problem present in a small number of patients with chronic kidney disease (CKD). The mechanism underlying this resistant albuminuria remains unknown. Matrix metalloproteinases (MMPs) are involved in the pathophysiology of cardiovascular and renal diseases.

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice.

The aim of this study was to characterize alterations in vascular structure and mechanics in murine mesenteric arteries from obese non-hypertensive mice, as well as their relationship with adipokines. Four-week old C57BL/6J male mice were assigned either to a control (C, 10% kcal from fat) or a high-fat diet (HFD, 45% kcal from fat) for 32weeks. HFD animals weighed 30% more than controls (p<0.

Vascular AMPK as an attractive target in the treatment of vascular complications of obesity.

The key for the survival of all organisms is the regulation and control of energy metabolism. Thus, several strategies have evolved in each tissue in order to balance nutrient supply with energy demand. Adenosine monophosphate-activated protein kinase (AMPK) is now recognized as a key participant in energy metabolism.

Mild caloric restriction reduces blood pressure and activates endothelial AMPK-PI3K-Akt-eNOS pathway in obese Zucker rats.

Genetic obesity models exhibit endothelial dysfunction associated to adenosine monophosphate-activated protein kinase (AMPK) dysregulation. This study aims to assess if mild short-term caloric restriction (CR) restores endothelial AMPK activity leading to an improvement in endothelial function. Twelve-week old Zucker lean and obese (fa/fa) male rats had access to standard chow either ad libitum (AL, n=8) or 80% of AL (CR, n=8) for two weeks.

High-fat diet induces endothelial dysfunction through a down-regulation of the endothelial AMPK-PI3K-Akt-eNOS pathway.

Scope: Activation of endothelial adenosine monophosphate-activated protein kinase (AMPK) contributes to increase nitric oxide (NO) availability. The aim of this study was to assess if high-fat diet (HFD)-induced endothelial dysfunction is linked to AMPK deregulation.

Methods And Results: Twelve-week-old Sprague Dawley male rats were assigned either to control (10 kcal % from fat) or to HFD (45 kcal % from fat) for 8 wk.

Development of albuminuria and enhancement of oxidative stress during chronic renin-angiotensin system suppression.

Objective: Albuminuria has been recently described in hypertensive patients under chronic renin-angiotensin system (RAS) suppression. We investigated whether this fact could be related to an increase in oxidative stress.

Methods: We examined normoalbuminuric and albuminuric patients in stage 2 chronic kidney disease, both with more than 2 years of RAS blockade.

Imbalance between pro and anti-oxidant mechanisms in perivascular adipose tissue aggravates long-term high-fat diet-derived endothelial dysfunction.

Background: The hypothesis of this study is that long-term high-fat diets (HFD) induce perivascular adipose tissue (PVAT) dysfunction characterized by a redox imbalance, which might contribute to aggravate endothelial dysfunction in obesity.

Methods And Results: C57BL/6J mice were fed either control or HFD (45% kcal from fat) for 32 weeks. Body weight, lumbar and mesenteric adipose tissue weights were significantly higher in HFD animals compared to controls.

Mechanisms of perivascular adipose tissue dysfunction in obesity.

Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT) was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta.

Remodeling of energy metabolism and absence of electrophysiological changes in the heart of obese hyperleptinemic mice. New insights into the pleiotropic role of leptin.

Dietary treatment with high-fat diets (HFD) triggers diabetes and hyperleptinemia, concomitantly with a partial state of leptin resistance that affects hepatic and adipose tissue but not the heart. In this context, characterized by widespread steatosis, cardiac lipid content remains unchanged. As previously reported, HFD-evoked hyperleptinemia could be a pivotal element contributing to increase fatty-acid (FA) metabolism in the heart and to prevent cardiac steatosis.

Dissecting the genetic predisposition to albuminuria and endothelial dysfunction in a genetic rat model.

Objective: The Munich Wistar Frömter (MWF) rat develops progressive spontaneous albuminuria largely attributable to quantitative trait loci on rat chromosome (RNO)6 and RNO8, respectively. We tested the hypothesis whether quantitative trait loci on these chromosomes are linked to both albuminuria and endothelial dysfunction.

Methods: Experiments were performed in male 12-week-old MWF, Wistar Kyoto (WKY), spontaneously hypertensive rat (SHR) and consomic MWF-6 and MWF-8 rats, in which RNO6 or RNO8 was replaced by the respective SHR chromosome (n = 10 per strain).

Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension.

Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone.

A reduction in the amount and anti-contractile effect of periadventitial mesenteric adipose tissue precedes hypertension development in spontaneously hypertensive rats.

The aim of this study was to determine whether alterations in periadventitial adipose tissue and its anti-contractile effect precede hypertension development. We used 4-week-old male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR), which were pre-hypertensive. Vascular function was studied in the perfused mesenteric bed (MB, 1.

Transient occurrence of an ebulin-related D-galactose-lectin in shoots of Sambucus ebulus L.

Young shoots of Sambucus ebulus L. contain a monomeric d-galactose binding lectin (SELlm), which disappears upon shoot development, and was previously undetected since it co-purifies with the non-toxic type 2 ribosome-inactivating protein ebulin l and the dimeric lectin SELld. Molecular cloning of cDNA coding for SELlm and mass spectrometry analysis revealed a protein with a molecular mass of 34,239 Da, which displays 80%, 77% and 45% of amino acid sequence identity with the ebulin l-B chain, SELld and ricin-B chain, respectively.

Over-expression of GTP-binding proteins and GTPase activity in mouse astrocyte membranes in response to Theiler's murine encephalomyelitis virus infection.

Intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV) induces a demyelinating disease that resembles human multiple sclerosis. In order to delineate the early events in this virus-induced neuroinflammatory disease, we have analyzed global GTPases gene activation following TMEV infection of murine brain astrocytes. DNA hybridization microchip analysis demonstrated that 10 sequences described as GTPbinding proteins and GTPases in different protein databases were over-expressed, in response to this infectious agent in astroglial cells.

Perivascular adipose tissue and mesenteric vascular function in spontaneously hypertensive rats.

Objective: Perivascular adipose tissue of normotensive rats releases a transferable factor that induces relaxation by opening voltage-dependent K+ (Kv) channels. The relevance of these observations to hypertension is unknown.

Methods And Results: We characterized mesenteric perivascular adipose tissue from 3-month-old Wistar Kyoto rats (WKY) and aged-matched spontaneously hypertensive rats (SHR).

Specific dose-dependent damage of Lieberkühn crypts promoted by large doses of type 2 ribosome-inactivating protein nigrin b intravenous injection to mice.

Nigrin b is a non-toxic type 2 ribosome-inactivating protein as active as ricin at ribosomal level but 10(5) and 5 x 10(3) times less toxic for animal cell cultures and mice, respectively, than ricin. The purpose of the present study was to analyze the effects of intravenous injection of large amounts of nigrin b to the mouse. Injection through the tail vein of 16 mg/kg body weight killed all mice studied before 2 days.

Expression and functional properties of group I metabotropic glutamate receptors in bovine chromaffin cells.

We demonstrate the presence and functional properties of Group I metabotropic glutamate receptors (mGluRs) expressed in chromaffin cells. Immunocytochemical techniques revealed that two mGluR subtypes (mGluR1alpha and mGluR5) are expressed in chromaffin cells, located in both the cytoplasmic membrane and the cytosol surrounding the nucleus. These mGluRs are functionally active on catecholamine (CA) secretion in chromaffin cells because both (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) and the specific agonist of Group I mGluRs, (S)-3,5-dihydroxyphenylglycine (DHPG), were able to stimulate the release of CAs (adrenaline and noradrenaline) in a dose-response manner.

Expression of interferon-gamma receptors on murine oligodendrocytes and its regulation by cytokines and mitogens.

Interferon-gamma (IFN-gamma) is a cytokine known to exert an important immunological role on astrocytes and oligodendrocytes. As a receptor for IFN-gamma has been demonstrated on murine astrocytes, we have searched for a specific receptor on the cell surface of pure mouse oligodendrocytes maintained in tissue culture. Using recombinant murine IFN-gamma labelled with 125I, we have established the basic physicochemical parameters of the binding.