Natriuretic peptides and cardiovascular damage in the metabolic syndrome. Molecular mechanisms and clinical implications

Natriuretic peptides are endogenous antagonists of vasoconstrictor and salt- and water-retaining systems in the body's defence against blood pressure elevation and plasma volume expansion, through direct vasodilator, diuretic and natriuretic properties. In addition, natriuretic peptides may play a role in the modulation of the molecular mechanisms involved in metabolic regulation and cardiovascular remodelling. The metabolic syndrome is characterized by visceral obesity, hyperlipidaemia, vascular inflammation and hypertension, which are linked by peripheral insulin resistance. Increased visceral adiposity may contribute to the reduction in the circulating levels of natriuretic peptides. The dysregulation of neurohormonal systems, including the renin-angiotensin and the natriuretic peptide systems, may in turn contribute to the development of insulin resistance in dysmetabolic patients. In obese subjects with the metabolic syndrome, reduced levels of natriuretic peptides may be involved in the development of hypertension, vascular inflammation and cardio vascular remodelling, and this may predispose to the development of cardiovascular disease. The present review summarizes the regulation and function of the natriuretic peptide system in obese patients with the metabolic syndrome and the involvement of altered bioactive levels of natriuretic peptides in the pathophysiology of cardiovascular disease in patients with metabolic abnormalities

Feasibility study and porting of the damped least square algorithm on FPGA

Modern embedded computing platforms used within Cyber-Physical Systems (CPS) are nowadays leveraging more and more often on heterogeneous computing substrates, such as newest Field Programmable Gate Array (FPGA) devices. Compared to general purpose platforms, which have a fixed datapath, FPGAs provide designers the possibility of customizing part of the computing infrastructure, to better shape the execution on the application needs/features, and offer high efficiency in terms of timing and power performance, while naturally featuring parallelism. In the context of FPGA-based CPSs, this article has a two fold mission. On the one hand, it presents an analysis of the Damped Least Square (DLS) algorithm for a perspective hardware implementation. On the other hand, it describes the implementation of a robotic arm controller based on the DLS to numerically solve Inverse Kinematics problems over a heterogeneous FPGA. Assessments involve a Trossen Robotics WidowX robotic arm controlled by a Digilent ZedBoard provided with a Xilinx Zynq FPGA that computes the Inverse Kinematic

Real-Time neural signal decoding on heterogeneous MPSocs based on VLIW ASIPs

An important research problem, at the basis of the development of embedded systems for neuroprosthetic applications, is the development of algorithms and platforms able to extract the patient's motion intention by decoding the information encoded in neural signals. At the state of the art, no portable and reliable integrated solutions implementing such a decoding task have been identified. To this aim, in this paper, we investigate the possibility of using the MPSoC paradigm in this application domain. We perform a design space exploration that compares different custom MPSoC embedded architectures, implementing two versions of a on-line neural signal decoding algorithm, respectively targeting decoding of single and multiple acquisition channels. Each considered design points features a different application configuration, with a specific partitioning and mapping of parallel software tasks, executed on customized VLIW ASIP processing cores. Experimental results, obtained by means of FPGA-based prototyping and post-floorplanning power evaluation on a 40nm technology library, assess the performance and hardware-related costs of the considered configurations. The reported power figures demonstrate the usability of the MPSoC paradigm within the processing of bio-electrical signals and show the benefits achievable by the exploitation of the instruction-level parallelism within tasks

Occurrence of Fipronil in residential house dust in the presence and absence of pets: a hint for a comprehensive toxicological assessment

The presence of the insecticide Fipronil and its main products of toxicological relevance, namely Sulfone and Desulfinyl, was assessed in 161 residential house dust samples in the absence (N = 101) and presence (N = 60) of cats and dogs in Italy. High-resolution mass spectrometry analysis revealed a significant difference (p < 0.001) in the dust contamination in the presence of pets (median: 467 vs. 24 ng/g dry weight), even if the highest value was found in the absence of pets (82,069 vs. 67,799 ng/g dry weight). Fipronil intake estimates from dust in toddlers, computed according to US-EPA and EU-ECHA guidelines, ranged from 333 to 556 and from 20 to 34 ng/kg per day for acute and chronic scenario, respectively. Dust seemed not able itself to lead to Fipronil overexposure with respect to acute and chronic toxicity health-based guidance values. Kittens were potentially overexposed to Fipronil under both acute (26,076 ng/kg per day) and chronic (1,633 ng/kg per day) scenarios. The mild symptomatology associated with acute intoxication could possibly determine case underreporting within pharmacosurveillance schemes. Its administration was estimated in 7.3\u20139.7 tons per year. Such a range suggests its prudent use under strict veterinary control to prevent pest resistance and ecotoxicological outcomes

No association between chromosome 12p13 single nucleotide polymorphisms and early-onset ischemic stroke

[No abstract available

The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes

In the present study, we tested the hypothesis that chronic treatment with the direct rennin inhibitor aliskiren improves the remodelling of resistance arteries in dTGR (double-transgenic rats). dTGR (5 weeks) were treated with aliskiren (3 mg/kg of body mass per day) or ramipril (1 mg/kg of body mass per day) for 14 days and compared with age-matched vehicle-treated dTGR. BP (blood pressure) was similarly reduced in both aliskiren-treated and ramipril-treated rats compared with control dTGR (167± 1 and 169± 2 mmHg compared with 197± 4 mmHg respectively; P<0.05). The M/L (media-to-lumen) ratio assessed on pressurized preparations was equally reduced in aliskiren-treated and ramipril-treated rats compared with controls (6.3± 0.5 and 6.4±0.2% compared with 9.8± 0.4% respectively; P<0.05). Endothelium-dependent and -independent relaxations were similar among the groups. L-NAME (NG-nitro-L-arginine methyl ester) significantly reduced acetylcholine-induced dilation in drug-treated dTGR. This effect was significantly more prominent in aliskiren-treated rats. eNOS (endothelial NO synthase) expression showed a 2-fold increase only in aliskiren-treated dTGR as compared with controls (P<0.01) and ramipril-treated dTGR (P<0.05). Plasma nitrite, as an index of NO production, was significantly increased in dTGR treated with either aliskiren or ramipril compared with controls. Only aliskiren induced a 2-fold increase in plasma nitrite, which was significantly greater than that induced by ramipril (P<0.05). gp91phox expression and ROS (reactive oxygen species) production in aorta were significantly and similarly reduced by both drugs. In conclusion, equieffective hypotensive doses of aliskiren or ramipril reduced the M/L ratio of mesenteric arteries and improved oxidative stress in dTGR. However, only aliskiren increased further NO production in the vasculature. Hence, in dTGR, direct renin inhibition induces favourable effects similar to that induced by ACE (angiotensin-converting enzyme) inhibition in improving vascular remodelling through different mechanisms. © The Authors Journal compilation. 2013 Biochemical Society

Brain overexpression of uncoupling protein-2 (Ucp2) delays renal damage and stroke occurrence in stroke-prone spontaneously hypertensive rats

The downregulation of uncoupling protein-2 (UCP2) is associated with increased brain and kidney injury in stroke-prone spontaneously hypertensive rats (SHRSP) fed with a Japanese style hypersodic diet (JD). Systemic overexpression of UCP2 reduces organ damage in JD-fed SHRSP. We examined the effect of brain-specific UCP2 overexpression on blood pressure (BP), stroke occurrence and kidney damage in JD-fed SHRSP. Rats received a single i.c.v. injection of a lentiviral vector encoding UCP2 (LV-UCP2), or an empty vector. The brain delivery of LV-UCP2 significantly delayed the occurrence of stroke and kidney damage. The large reduction of proteinuria observed after LV-UCP2 injection was unexpected, because BP levels were unchanged. At the time of stroke, rats treated with LV-UCP2 still showed a large UCP2 upregulation in the striatum, associated with increases in OPA1 and FIS1 protein levels, and reductions in PGC1-α, SOD2, TNFα mRNA levels and NRF2 protein levels. This suggested UCP2 overexpression enhanced mitochondrial fusion and fission and reduced oxidative damage and inflammation in the striatum of JD-fed SHRSP rats. Our data suggest the existence of central mechanisms that may protect against hypertension-induced organ damage independently of BP, and strengthen the suitability of strategies aimed at enhancing UCP2 expression for the treatment of hypertensive damage

Abnormalities of sodium handling and of cardiovascular adaptations during high salt diet in patients with mild heart failure.

BACKGROUND: Sodium retention and hormonal activation are fundamental hallmarks in congestive heart failure. The present study was designed to assess the ability of patients with asymptomatic to mildly symptomatic heart failure and no signs or symptoms of congestion to excrete ingested sodium and to identify possible early abnormalities of hormonal and hemodynamic mechanisms related to sodium handling. METHODS AND RESULTS: The effects of a high salt diet (250 mEq/day for 6 days) on hemodynamics, salt-regulating hormones, and renal excretory response were investigated in a balanced study in 12 untreated patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (NYHA class I-II, ejection fraction < 50%) (HF) and in 12 normal subjects, who had been previously maintained a 100 mEq/day NaCl diet. In normal subjects, high salt diet was associated with significant increases of echocardiographically measured left ventricular end-diastolic volume, ejection fraction, and stroke volume (all P < .001) and with a reduction of total peripheral resistance (P < .001). In addition, plasma atrial natriuretic factor (ANF) levels increased (P < .05), and plasma renin activity and aldosterone concentrations fell (both P < .001) in normals in response to salt excess. In HF patients, both left ventricular end-diastolic and end-systolic volumes increased in response to high salt diet, whereas ejection fraction and stroke volume failed to increase, and total peripheral resistance did not change during high salt diet. In addition, plasma ANF levels did not rise in HF in response to salt loading, whereas plasma renin activity and aldosterone concentrations were as much suppressed as in normals. Although urinary sodium excretions were not significantly different in the two groups, there was a small but systematic reduction of daily sodium excretion in HF, which resulted in a significantly higher cumulative sodium balance in HF than in normals during the high salt diet period (P < .001). CONCLUSIONS: These results show a reduced ability to excrete a sodium load and early abnormalities of cardiac and hemodynamic adaptations to salt excess in patients with mild heart failure and no signs or symptoms of congestion

Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention. FUNDING: British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7