In vitro profiling of endothelial volatile organic compounds under resting and pro-inflammatory conditions.

INTRODUCTION: The evaluation of volatile organic compounds(VOCs) emitted by human body offers a unique tool to set up new non-invasive devices for early diagnosis and long-lasting monitoring of most human diseases. However, their cellular origin and metabolic fate have not been completely elucidated yet, thus limiting their clinical application. Endothelium acts as an interface between blood and surrounding tissues. As such, it adapts its physiology in response to different environmental modifications thus playing a role in the pathogenesis of many metabolic and inflammatory diseases. OBJECTIVES: Since endothelium specifically reshapes its physiologic functions upon environmental changes the objective of this study was to evaluate if and how pro-inflammatory stimuli affect VOC metabolism in endothelial cell in culture. METHODS: Gas chromatography with mass spectrometric detection was applied to profile VOCs in the headspace of cultured endothelial cells (EC) in the absence or presence of the pro-inflammatory stimulus lipopolysaccharide (LPS). RESULTS: We observed that, under resting conditions, EC affected the amount of 58 VOCs belonging to aldehyde, alkane and ketone families. Among these, LPS significantly altered the amount of 15 VOCs. ROC curves show a perfect performance (AUC = 1) for 10 metabolites including 1-butanol, 3-methyl-1-butanol and 2-ethyl-1-hexanol. DISCUSSION: The emission and uptake of the aforementioned VOCs disclose potential unexplored metabolic pathways for EC that deserve to be investigated. Overall, we identified new candidate VOC potentially exploitable, upon experimental confirm in in vivo model of disease, as potential biomarkers of sepsis and pro-inflammatory clinical settings.

Omega-3 fatty acids, inflammation and angiogenesis: basic mechanisms behind the cardioprotective effects of fish and fish oils.

Atherosclerosis is now widely accepted to be an inflammatory disease, characterized by degenerative as well as proliferative changes and extracellular accumulation of lipid and cholesterol, in which an ongoing inflammatory reaction plays an important role both in initiation and progression/destabilization, converting a chronic process into an acute disorder. Neovascularization has also been recognized as an important process for the progression/destabilization of atherosclerotic plaques. In fact, vulnerable atherosclerotic plaques prone to rupture are characterized by an enlarged necrotic core, containing an increased number of vasa vasorum, apoptotic macrophages, and more frequent intraplaque haemorrhage. Various functional roles have been assigned to intimal microvessels, however the relationship between the process of angiogenesis and its causal association with the progression and complications of atherosclerosis are still challenging and controversial. In the past 30 years, the dietary intake of omega-3 (n-3) polyunsaturated fatty acids--mainly derived from fish--has emerged as an important way to modify cardiovascular risk through beneficial effects on all stages of atherosclerosis, including plaque angiogenesis. This review specifically focuses on the modulating effects of n-3 fatty acids on molecular events involved in early and late atherogenesis, including effects on endothelial expression of adhesion molecules, as well as pro-inflammatory and pro-angiogenic enzymes. By accumulating in endothelial membrane phospholipids, omega-3 fatty acids have been shown to decrease the transcriptional activation of several genes through an attenuation of activation of the nuclear factor-kappaB system of transcription factors. This occurs secondary to decreased generation of intracellular reactive oxygen species. This series of investigations configures a clear example of nutrigenomics--i.e., how nutrients may affect gene expression, ultimately affecting a wide spectrum of human diseases.

Obstructive sleep apnoea syndrome: a new paradigm by chronic nocturnal intermittent hypoxia and sleep disruption.

Obstructive sleep apnoea syndrome (OSAS) is associated with severe cerebro-cardiovascular morbidity and mortality. It is an independent risk factor for atherosclerosis, arterial thrombosis and metabolic syndrome, and recently has been associated with an increased incidence of cancer and death. A causal link between OSAS and atherosclerosis has been partially established. Recent research on atherosclerosis in OSAS has focused on thrombotic tendency and blood viscosity, providing new insight into disease mechanisms. Hypoxia is a critical pathophysiological element in OSAS that leads to intensive sympathetic activity, in association with inflammation, oxidative stress and procoagulant activity. Hypoxia and the induction of oxidative stress can simultaneously represent an underlying mechanism in the pathogenesis of cancer development and progression. This mini-review will discuss the latest findings on the association and potential relationship between OSA and pathological vascular sequelae.

Vascular effects of the Mediterranean diet part I: anti-hypertensive and anti-thrombotic effects.

This review summarizes available evidence on the beneficial effects of inorganic nitrates and the monounsaturated fatty acid (MUFA) oleic acid, largely contained in Mediterranean diet, on blood pressure and coagulation activity. Inorganic nitrate. Normal vascular function requires NO production from the 1-arginine-NO synthase (NOS) pathway. This process is defective in conditions of local hypoxia, and here nitrite can substitute for 1-arginine-NOS derived NO. In this context, NO generation from the nitrate-nitrite-NO pathway mostly derived from green leafy vegetables appears to be an alternative source for NOS-dependent NO production, ensuring NO bioavailability also in situations when the endogenous 1-arginine/NO synthase pathway is dysfunctional or physiologically reduced in local hypoxic conditions. Olive oil and oleic acid. In addition to effects on lipoprotein metabolism and oxidation, the beneficial effects of oleic acid occur also on coagulation activity, namely on coagulation factor VII (FVII). Normally, a substantial increase of FVII coagulant activity (FVIIc) occurs within 2-3h after a fatty meal and persists for several hours thereafter. When a background diet high in MUFA is consumed, a lower post-prandial increase of FVIIc takes place.