Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population.

Background: Carotid atherosclerosis represents one of the complications of diabetes mellitus. In particular, plaque instability contributes to disease progression and stroke incidence. High mobility group box-1 (HMGB1) is a nuclear protein involved in promotion and progression of atherosclerosis and cardiovascular diseases.

Serum high mobility group box-1 and osteoprotegerin levels are associated with peripheral arterial disease and critical limb ischemia in type 2 diabetic subjects.

Background: High mobility group box-1 (HMGB-1) is a nuclear protein also acting as inflammatory mediator, whilst osteoprotegerin (OPG), member of tumor necrosis factor receptor superfamily, is indicated as marker of vascular calcification. Peripheral artery disease (PAD) and type 2 diabetes (T2D) are clinical conditions characterized by elevated serum inflammatory markers and vascular calcification enhancement. The aim of this study was to investigate the potential role of HMGB-1, OPG and several inflammatory mediators such as C-reactive protein (HsCRP), tumor necrosis factor-alpha and interleukin-6 (IL-6) on the presence and severity of peripheral artery disease in patients with T2D.

Increased FGF23 serum level is associated with unstable carotid plaque in type 2 diabetic subjects with internal carotid stenosis.

Background: The object of this study was to investigate the potential role of FGF23 on plaque stability in type 2 diabetic patients with internal carotid artery stenosis.

Methods: In this retrospective observational study, we analyzed FGF23 serum level in 361 type 2 diabetic patients with internal carotid artery stenosis undergoing carotid endarterectomy and in 598 diabetic controls without carotid atherosclerosis.

Results: We found that FGF23 median serum levels was significantly higher in patients than in diabetic controls [67.

Identification of a potential proinflammatory genetic profile influencing carotid plaque vulnerability.

Objective: Atherosclerosis and vascular remodeling after injury are driven by inflammation and mononuclear cell infiltration. Unstable atherosclerotic plaques are characterized by a large necrotic core. In this study we investigated the distribution and interaction between gene polymorphisms encoding proinflammatory molecules in an Italian population with internal carotid artery stenosis (ICAS).

TNFRSF11B gene polymorphisms increased risk of peripheral arterial occlusive disease and critical limb ischemia in patients with type 2 diabetes.

Aims: Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. OPG has been hypothesized to modulate vascular functions; however, its role in mediating atherosclerosis is controversial. Epidemiological data in patients with cardiovascular disease (CVD) indicate that OPG serum levels are associated with several inflammatory markers, myocardial infarction events, and calcium scores, suggesting that OPG may be causative for CVD.

Effect of proinflammatory gene polymorphisms on the risk of Alzheimer's disease.

Background: A number of studies associate Alzheimer's disease (AD) with APOE polymorphism and alleles which favor the increased expression of immunological mediators such as cytokines or acute-phase proteins.

Objective: In this study we evaluated the distribution of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in individuals with AD. We also investigated whether a synergistic effect of these proinflammatory gene polymorphisms on the risk of AD could be hypothesized.

Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients.

Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. The present study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved in ischemic stroke in an Italian population with diabetes. Participants in a retrospective case-control study included 364 diabetic patients (180 males, 184 females) with history of ischemic stroke and 492 diabetic subjects without history of ischemic stroke (252 males, 240 females).

Cilostazol promotes angiogenesis after peripheral ischemia through a VEGF-dependent mechanism.

Background/objectives: Cilostazol has been found to be effective for the treatment of intermittent claudication (IC). This compound has several beneficial effects on platelet aggregation, serum lipids and endothelial cells, but how these might relate to improvements in walking is not entirely understood. The aim of this work was to investigate the effects of cilostazol on angiogenic response in a murine model of peripheral ischemia and to clarify the underlying molecular mechanisms of that response.

Assessment of the genetic effects of polymorphisms in the osteoprotegerin gene, TNFRSF11B, on serum osteoprotegerin levels and carotid plaque vulnerability.

Background And Purpose: Osteoprotegerin (OPG) is a secretory glycoprotein which belongs to the tumor necrosis factor receptor family. Various mechanisms have been suggested by which calcification might alter atherosclerotic plaque stability, but the significance of this intimal calcification is controversial. High concentrations of OPG have been associated with the presence of vascular and cardiovascular diseases.

Glycaemic variability affects ischaemia-induced angiogenesis in diabetic mice.

The aim of the present study was to investigate the role of GV (glycaemic variability) in diabetic vascular complications and to explore the molecular pathways modulated by glycaemic 'swings'. We developed a murine model. A total of 30 diabetic mice received once daily basal insulin administration plus two oral boluses of glucose solution (GV group, named 'V') and 30 diabetic mice received once daily basal insulin plus two oral boluses of saline solution (stable hyperglycaemia group, named 'S') for a period of 30 days.

High-mobility group box-1 protein promotes angiogenesis after peripheral ischemia in diabetic mice through a VEGF-dependent mechanism.

Objective: High-mobility group box-1 (HMGB1) protein is a nuclear DNA-binding protein released from necrotic cells, inducing inflammatory responses and promoting tissue repair and angiogenesis. Diabetic human and mouse tissues contain lower levels of HMGB1 than their normoglycemic counterparts. Deficient angiogenesis after ischemia contributes to worse outcomes of peripheral arterial disease in patients with diabetes.

Vitamin E and enzymatic/oxidative stress-driven oxysterols in amnestic mild cognitive impairment subtypes and Alzheimer's disease.

Oxidative stress,which contributes to neuronal damage, is thought to be a pathophysiologicalmechanism of Alzheimer's disease (AD). Markers of oxidative stress may appear early in the preclinical, mild cognitive impairment (MCI) phase of AD.We investigated the interaction among enzymatic-derived oxysterols (24S-hydroxycholesterol and 27-hydroxycholesterol), markers of oxidative stress, including free radical-related oxysterols (7 hydroxycholesterol and 7-ketocholesterol), and vitamin E in AD patients and two amnestic MCI subtypes, amnestic single-domain MCI (a-MCI) subjects, and multidomain MCI (md-MCI) subjects, compared to healthy control subjects (HC).

Management of nonvalvular atrial fibrillation: a comprehensive approach.

Atrial fibrillation is the most common arrhythmia in clinical practice, may coexist with conditions common to both cardiovascular and noncardiovascular diseases and is associated with considerable morbidity and mortality. Atrial fibrillation is often asymptomatic and diagnosed only when it has caused a potentially serious complication, such as an ischemic stroke. When atrial fibrillation has been identified, 2 objectives have to be addressed--the antiarrhythmic therapy based on rate control or rhythm control, and prevention of thromboembolism.

Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPARgamma stimulation.

Background: Type 2 diabetes mellitus (T2DM) is commonly associated with both microvascular and macrovascular complications and a strong correlation exists between glycaemic control and the incidence and progression of vascular complications. Pioglitazone, a Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligand indicated for therapy of type T2DM, induces vascular effects that seem to occur independently of glucose lowering.

Methods: By using a hindlimb ischemia murine model, in this study we have found that pioglitazone restores the blood flow recovery and capillary density in ischemic muscle of diabetic mice and that this process is associated with increased expression of Vascular Endothelial Growth Factor (VEGF).

Association of cholesterol oxidation and abnormalities in fatty acid metabolism in cystic fibrosis.

Background: Disarrangement in fatty acids and oxidative stress are features of cystic fibrosis. Cholesterol is very sensitive to oxidative stress.

Objectives: The objectives were to examine whether cholesterol oxidation products are altered in cystic fibrosis and whether they are associated with fatty acids and with characteristics of the disease state.

VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis.

Background & Aims: Vascular endothelial growth factor A (VEGF-A) mediates angiogenesis and might also have a role in inflammation and immunity. We examined whether VEGF-A signaling has a role in inflammatory bowel disease (IBD).

Methods: Expression levels of VEGF-A, and its receptors VEGFR-1 and VEGFR-2, were examined in samples from patients with IBD and compared with those of controls.

Sonic hedgehog regulates angiogenesis and myogenesis during post-natal skeletal muscle regeneration.

Sonic hedgehog (Shh) is a morphogen-regulating crucial epithelial-mesenchymal interactions during embryonic development, but its signalling pathway is considered generally silent in post-natal life. In this study, we demonstrate that Shh is de novo expressed after injury and during regeneration of the adult skeletal muscle. Shh expression is followed by significant up-regulation of its receptor and target gene Ptc1 in injured and regenerating muscles.

Peroxisome proliferator-activated receptor alpha is crucial for iloprost-induced in vivo angiogenesis and vascular endothelial growth factor upregulation.

We have previously demonstrated that iloprost, a stable prostacyclin (PGI(2)) analogue, induces angiogenesis in vivo, through a vascular endothelial growth factor (VEGF)-dependent mechanism. In this study, we demonstrate that iloprost-induced angiogenesis and VEGF upregulation are modulated by peroxisome proliferator-activated receptor-alpha (PPARalpha), a ligand-inducible transcription factor that belongs to the nuclear hormone receptor superfamily and plays multiple biological activities in the vascular system. We show that iloprost is unable to induce angiogenesis in mice lacking the PPARalpha gene (PPARalpha-/- mice).

Selective activation of peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma induces neoangiogenesis through a vascular endothelial growth factor-dependent mechanism.

Objective: Peroxisome proliferator-activated receptors (PPARs) are therapeutic targets for fibrates and thiazolidinediones, which are commonly used to ameliorate hyperlipidemia and hyperglycemia in type 2 diabetes. In this study, we evaluated whether activation of PPAR alpha and PPAR gamma stimulates neoangiogenesis.

Research Design And Methods: We used selective synthetic PPAR alpha and PPAR gamma agonists and investigated their angiogenic potentials in vitro and in vivo.

Analysis of functional polymorphisms of metalloproteinase genes in persons with vascular dementia and Alzheimer's disease.

Background: Vascular dementia (VAD) and Alzheimer's disease (AD) may share common neuropathological mechanisms. Matrix metalloproteinases (MMPs) may induce destruction of the extracellular matrix, neuronal dysfunction, and death. Increased expression of these molecules has been found in a number of neurological diseases, including cerebral ischemia and AD.

Proinflammatory genetic profiles in subjects with history of ischemic stroke.

Background And Purpose: Proinflammatory genetic profiles, resulting from the combination of single nucleotide polymorphisms in genes encoding inflammatory molecules, may contribute to the development and progression of cardiovascular diseases. We evaluated the association between history of ischemic stroke and genetic profiles determined by the synergistic effects of polymorphisms in genes encoding prototypical inflammatory proteins.

Methods: The study included 237 individuals with history of ischemic stroke and 223 age-matched and gender-matched controls.

Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism and risk of Alzheimer's disease in Italians.

Monocyte chemoattractant protein-1 (MCP-1) is a key molecule for monocyte chemotaxis and tissue extravasation and for the modulation of leukocyte function during inflammation. Upregulation of MCP-1 may occur in the brain of subjects affected by Alzheimer's disease (AD) and MCP-1 levels in plasma and cerebrospinal fluid have been proposed as biological markers for the inflammatory process that accompanies AD pathogenesis. Importantly, serum levels and biological activity of MCP-1 protein are strongly influenced by a single nucleotide polymorphism occurring at position -2518 of the MCP-1 gene promoter.