Serum levels of nitric oxide and endothelin-1 in vasculopathy managed with hyperbaric oxygen therapy.

Roles of nitric oxide (NO) and endothelin-1 (ET-1) in the local regulation of blood flow under physiological conditions are important and well known, while data on their effects and interactions in conditions of hyperbaric hyperoxia is still insufficient. This was a prospective observational study which included patients who underwent hyperbaric oxygen therapy (HBOT) in accordance with existing therapeutic protocol for peripherial arterial disease (PAD) during time period of six months, between january and july of 2016. Clinical stage of PAD according to Fontain was taken into account, as well as risk factors, demographic, anthropometric and clinical characteristics of studied patients. The study included 64 patients with a mean age (±Sd) 60.2±12.7 years, of whom 28 were female. Patients' NO serum levels in all observed categories before and after HBOT were not signifficantly different, except for stage II PAD (NObefore HBOT 21.9±9.6 vs. NOafter HBOT 26.2±12.1 (p = 0.04)). On the contrary, in all studied patients ET-1 level increased signifficantly after HBOT (ET-1before HBOT 4.2±11.6 vs. ET-1after 18.3±21.0 (p < 0.001)). Treatment of PAD using HBOT leads to the predominance of vasoconstrictor effects probably caused by elevation of serum ET-1 concentrations, while other factors such as exposure time to hyperbaric conditions, activation of antioxidant molecules, and the influx of other interfering substances must be considered in interpreting the effects of NO molecules.

Association of plasma homocysteine level with vaso-occlusive crisis in sickle cell anemia patients of Odisha, India.

Vascular complications of sickle cell anemia (SCA) are influenced by many factors. Elevated plasma homocysteine (Hcy) is supposed to be an independent risk factor and is either genetic or nutritional origin. The present study evaluated the plasma Hcy level, MTHFR C677T gene polymorphism, effect of folic acid (FA) supplementation' and hemato-biochemical parameters in SCA and their effect on the vaso-occlusive crisis (VOC) in SCA patients of an Asian-Indian haplotype population. One hundred twenty cases of SCA (HbSS) and 50 controls with normal hemoglobin(HbAA) were studied. It was found that the plasma Hcy level is significantly higher (p < 0.0001) in patients with SCA (22.41 ± 7.8 µmol/L) compared to controls (13.2 ± 4.4 µmol/L). Moreover, patients without FA supplementation had a significantly (p < 0.001) higher Hcy level (27 ± 7 µmol/L) compared to those with supplementation (17.75 ± 5.7 µmol/L). Turkey-Kramer multiple comparison tests show that there is a significant difference (p < 0.05) in HbF percent, hemoglobin (Hb), platelet count, serum bilirubin (direct:Bil-D and total:Bil-T), aspartate transaminase (AST), lactate dehydrogenase (LDH), and plasma Hcy levels between mild and severe VOC. Between moderate VOC and severe VOC, there was a significant difference (p < 0.05) in HbF%, Bil-D, AST, Hcy. Pearson correlation revealed that plasma Hcy had a significantly (p < 0.05) positive correlation with AST, serum bilirubin (indirect and total), LDH, jaundice, stroke, VOC per year, and hospitalization per year whereas it was inversely correlated with HbF percentage, Hb level, and FA treatment. In the study population, increased plasma Hcy level, hemolysis, and platelet activation were found to influence VOC in SCA.

Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis.

OBJECTIVES: Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins (VKDP) are associated with VS and VC and require vitamin K for activity. We conducted a systematic review and meta-analysis of: (1) the effect of vitamin K supplementation on VS and VC and (2) association of inactive VKDP levels with incident cardiovascular disease and mortality. METHODS: Two authors searched MEDLINE and Embase databases and Cochrane and ISRCTN registries for studies of vitamin K clinical trials that measured effects on VC, VS or VKDP and longitudinal studies assessing effect of VKDP on incident CVD or mortality. Random effects meta-analyses were performed. RESULTS: Thirteen controlled clinical trials (n=2162) and 14 longitudinal studies (n=10 726) met prespecified inclusion criteria. Vitamin K supplementation was associated with significant reduction in VC (-9.1% (95% CI -17.7 to -0.5); p=0.04) and VKDP (desphospho-uncarboxylated matrix Gla protein; -44.7% (95% CI -65.1 to -24.3), p<0.0001) and uncarboxylated osteocalcin; -12.0% (95% CI -16.7 to -7.2), p<0.0001) compared with control, with a non-significant improvement in VS. In longitudinal studies with median follow-up of 7.8 (IQR 4.9-11.3) years, VKDP levels were associated with a combined endpoint of CVD or mortality (HR 0.45 (95% CI 0.07 to 0.83), p=0.02). CONCLUSIONS: Supplementation with vitamin K significantly reduced VC, but not VS, compared with control. The conclusions drawn are limited by small numbers of studies with substantial heterogeneity. VKDP was associated with combined endpoint of CVD or mortality. Larger clinical trials of effect of vitamin K supplementation to improve VC, VS and long-term cardiovascular health are warranted. TRIAL REGISTRATION NUMBER: CRD42017060344.

Mangiferin inhibits high-fat diet induced vascular injury via regulation of PTEN/AKT/eNOS pathway.

Mangiferin (MAN), a naturally occurring polyphenol commonly found in mango and papaya. However, little is known its anti-vascular injury effects and the underlying mechanisms. This paper investigated the anti-vascular injury effect of MAN and the mechanisms in high-fat diet (HFD)-induced C57BL/6J mice and oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs). The levels of plasma lipid, inflammatory factors and nitric oxide (NO) in mice were evaluated. The expression levels of PI3K, AKT, eNOS, PTEN and their phosphorylated proteins were measured by western blots. In addition, the PTEN-siRNA HUVECs were also used. The result showed that MAN markedly decreased the plasma lipid, inflammatory level in HFD-induced vascular injury mice respectively. Furthermore, MAN alleviate ox-LDL-stimulated dysfunction of HUVECs, restored the diminished NO release, decreased the ROS generation, significantly increased the expression of p-Akt, p-eNOS, and decreased the expression of PTEN, but have no effect on PI3K. However, the protective effects of MAN were significantly reduced by co-treatment with PI3K inhibitor or abolished by eNOS inhibitor. In addition, MAN has no protective effect on ox-LDL induced PTEN-siRNA HUVECs injury. Collectively, MAN appeared to alleviate ox-LDL-stimulated dysfunction of HUVECs via the PTEN/Akt/eNOS signaling pathway, thus decrease vascular injury in HFD-administrated mice.

Homocysteine and Non-Cardiac Vascular Disease.

Elevated homocysteine (Hcy) levels are predictors of cardiovascular disease (CVD). Hyperhomocysteinemia has also been associated with total and CVD mortality. However, whether Hcy is just a marker or plays a causal role in CVD remains to be elucidated. In this narrative review, we discuss the associations between Hcy and non-cardiac vascular diseases, namely stroke, peripheral artery disease (PAD), carotid artery disease, chronic kidney disease (CKD), atherosclerotic renal artery stenosis (ARAS), abdominal aortic aneurysm (AAA) and erectile dysfunction (ED). The effects of several drugs on Hcy levels are also considered. Folic acid, vitamin B6 and B12 supplementation can significantly decrease circulating Hcy concentrations but their effects on CVD risk reduction are conflicting. No current guidelines recommend the routine screening of Hcy levels in patients with non-cardiac vascular diseases. Therefore, further research is needed to elucidate the use of Hcy in the clinical practice.

Natural antioxidant ice cream acutely reduces oxidative stress and improves vascular function and physical performance in healthy individuals.

OBJECTIVE: The formation of reactive oxygen species (ROS) contributes to the pathogenesis and progression of several diseases. Polyphenols have been shown to be beneficial against ROS. The aim of this study was to evaluate the effects of a natural antioxidant ice cream on oxidative stress, vascular function, and physical performance. METHODS: In this controlled, single-blind, crossover study, 14 healthy individuals were randomized to consume 100 g of either antioxidant ice cream containing dark cocoa powder and hazelnut and green tea extracts or milk chocolate ice cream (control ice cream). Participants were studied at baseline and 2 h after ingesting ice cream. Serum polyphenols, antioxidant status (ferric-reducing ability of plasma [FRAP]), nitric oxide (NOx) bioavailability, markers of oxidative stress (determination of reactive oxygen metabolites [d-ROMs] and hydrogen peroxide [H2O2]), endothelium function (flow-mediated dilation [FMD] and reactive hyperemia index [RHI]), and exercise tolerance (stress test) were assessed, and the double product was measured. RESULTS: Serum polyphenols (P < 0.001), NOx (P < 0.001), FRAP (P < 0.005), FMD (P < 0.001), and RHI (P < 0.05) increased significantly, oxidative stress decreased (d-Roms, P < 0.001; H2O2, P < 0.001), and the double product (P < 0.001) was improved only after antioxidant ice cream ingestion. No changes were found after control ice cream ingestion. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that a natural ice cream rich in polyphenols acutely improved vascular function and physical performance in healthy individuals through a reduction in oxidative stress.

Fibrinolytic effects of peroneal nerve stimulation in patients with lower limb vascular disease.

Patients with lower limb vascular disease are at an increased risk of thrombotic events. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) are important components of the fibrinolytic system, responsible for clot lysis. This study aimed to establish whether peroneal nerve stimulation (PNS) could promote fibrinolysis within a cohort of vascular patients. Ethical approval was obtained for this prospective case-controlled study. Patients were randomly assigned to active stimulation or control groups. Arterial flow measurements and venous blood samples were taken bilaterally at baseline and following 45 min of PNS. ELISA analysis for plasma t-PA and PAI-1 was performed utilizing commercially available kits. Statistical analysis evaluated the changes in t-PA and PAI-1 levels from baseline for the active (device active), passive (contralateral limb) and control limbs (inactive device applied).Seventy-seven participants were recruited: 30 claudicants (25 active and five controls), 25 patients postoperative infra-inguinal bypass grafts (19 active and six controls) and 22 patients with varicose veins (17 active and five controls). t-PA levels reduced significantly in all groups; however, intergroup analysis demonstrated no statistically significant difference when comparing the active, passive and control limbs (P = 0.079). PAI-1 levels decreased by 16.2% (34.0 ng/ml, SD 52.2) in the active limbs but only 3.6% (11.4 ng/ml, SD 47.4) and 2.6% (2.7 ng/ml, SD 21.3) in the passive and control limbs, respectively (intergroup analysis P < 0.001). No relationship between changes in flow and plasma of t-PA and PAI-1 were demonstrated. Peroneal nerve stimulation may augment fibrinolysis by decreasing plasma levels of PAI-1 levels in patients with lower limb arterial and venous disease.

Vitamin D deficiency and acute vaso-occlusive complications in children with sickle cell disease.

BACKGROUND: Vitamin D is increasingly recognized for its roles in non-skeletal disorders. Patients with sickle cell disease (SCD) have a high prevalence of vitamin D deficiency but data are limited with respect to possible associations between low vitamin D and acute vaso-occlusive complications. We examined whether vitamin D deficiency is associated with acute pain and acute chest syndrome (ACS) in children with SCD. PROCEDURE: A cross-sectional study was conducted in 95 children with SCD who had serum 25-hydroxyvitamin D (25-OHD) measured during comprehensive care examinations. History of acute pain and ACS within two years of obtaining 25-OHD was collected. Associations between 25-OHD levels and acute vaso-occlusive events were analyzed by logistic regression. Odds ratios and 95% confidence intervals were calculated for the risk of pain and ACS associated with vitamin D deficiency (25-OHD <20 ng/ml). RESULTS: Subjects were 3-20 years old (median 10.6); 48 males, 47 females; 46 African, 49 Hispanic; 72 SS, 20 SC, 1 S/ß(0) Thalassemia, and 2 S/ß(+) Thalassemia. Median 25-OHD was 16 ng/ml. Fifty-six (59%) were vitamin D-deficient. Thirty-one (33%) and 29 (31%) had at least one episode of pain and ACS, respectively. Serum 25-OHD was significantly associated with pain (P = 0.0121) but not with ACS (P = 0.628). Of those with pain, 73% (23/31) were vitamin D-deficient while 26% (8/31) had 25-OHD ≥20 ng/ml (P = 0.04, OR = 2.7, 95%CI = 1.05-6.94). CONCLUSIONS: Our findings emphasize the high prevalence of vitamin D deficiency and its potential association with acute pain in SCD. Correcting low vitamin D may offer a simple, low-cost intervention to help reduce acute vaso-occlusive complications.

Early endothelial nitrosylation and increased abdominal adiposity in Wistar rats after long-term consumption of food fried in canola oil.

OBJECTIVE: The aim of this study was to establish whether the long-term consumption of reused canola oil contributes to the development of dyslipidemia, obesity, and endothelial function. METHODS: Canola oil was used for one frying cycle (1 FC) of corn flour dough or reused 10 times (10 FC). Rats received chow diet (control) or supplemented with 7% raw oil (RO), 1 FC or 10 FC oil (n = 10 per group). Food consumption, blood pressure (BP), and body weight plasma glucose, plasma lipids were monitored. Vascular reactivity was analyzed using aorta rings stimulated with phenylephrine and acetylcholine. Nitrotyrosine presence in aorta rings was analyzed by immunohistochemistry. RESULTS: After 10 wk of follow-up, visceral adipose tissue was significantly more abundant in 1 FC (7.4 ± 0.6 g) and 10 FC (8.8 ± 0.7 g) than the RO (5.0 ± 0.2 g; P = 0.05 versus 10 FC group) or control group (2.6 ± 0.3 g; P = 0.05 versus all groups). Despite similar plasma cholesterol, triglycerides, and BP among groups, a significantly reduced acetylcholine-induced vascular relaxation was observed in the three groups receiving the oil-supplemented diet (47.2% ± 3.6%, 27.2% ± 7.7%, and 25.9% ± 7.6% of relaxation, for the RO, 1 FC, and 10 FC, respectively; P < 0.05 for all versus 62.4% ± 9.7% of the control group). Endothelial dysfunction was concomitant with the presence of nitrotyrosine residues at a higher extent in the groups that received heated oils compared with the RO group. CONCLUSION: High canola oil intake over 10 wk was associated with increased adipose tissue and early endothelial dysfunction probably induced by peroxinitrite formation. Such deleterious effects were significantly potentiated when the consumed oil had been used repeatedly for frying.

Active vitamin D and accelerated progression of aortic stiffness in hemodialysis patients: a longitudinal observational study.

BACKGROUND: We hypothesized that high-dose active vitamin D therapy in the form of alphacalcidol (α-calcidol), used to treat secondary hyperparathyroidism in chronic kidney disease, could lead to vascular calcification and accelerated progression of aortic stiffness. METHODS: We conducted an observational study in 85 patients on chronic hemodialysis, among which 70 were taking a weekly dose of α-calcidol of <2 µg and 15 were taking a weekly dose of ≥2 µg (pharmacological dose). Parathyroid hormone, 25-hydroxyvitamin D, fibroblast growth factor 23, and α-klotho were determined. Aortic stiffness was assessed by determination of carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. A multivariable regression model was used to evaluate the impact of pharmacological dose of α-calcidol on the progression of aortic stiffness. RESULTS: At baseline, clinical, biological, and hemodynamic parameters were similar. At follow-up, cf-PWV increased more in patients with pharmacological dose of α-calcidol (0.583±2.291 m/s vs. 1.948±1.475 m/s; P = 0.04). After adjustment for changes in mean blood pressure and duration of follow-up, pharmacological dose of α-calcidol was associated with a higher rate of progression of cf-PWV (0.969 m/s; 95% confidence interval = 0.111-1.827; P = 0.03), and this association persisted after further adjustments for parameters of mineral metabolism. CONCLUSIONS: In this study, pharmacological dose of α-calcidol was associated with accelerated progression of aortic stiffness. This study suggest that the vascular safety of active vitamin D posology may need to be specifically addressed in the treatment of chronic kidney disease-related bone mineral disorder.

Effect of short-term vitamin D supplementation on markers of vascular health in South Asian women living in the UK--a randomised controlled trial.

OBJECTIVE: Low vitamin D levels and risk factors for vascular disease are both common in South Asian women. This trial evaluated whether vitamin D supplementation could improve markers of vascular health in South Asian women with low 25-hydroxyvitamin D levels. METHODS: Parallel-group, double-blind, randomised placebo-controlled trial. Healthy South Asian women with baseline serum 25-hydroxyvitamin D levels of <75 nmol/L were randomised to receive a single dose of 100,000 units oral vitamin D3 or matching placebo. Outcomes were measured at baseline, 4 and 8 weeks. The primary outcome was change in endothelial function measured using brachial artery flow-mediated dilatation. Secondary outcomes included blood pressure, arterial stiffness, microvascular function measured using laser Doppler iontophoresis, insulin resistance, serum lipids, circulating markers of inflammation, thrombosis and adipokines. RESULTS: 50 women were randomised, 25 to each group. Mean age was 41 years; mean baseline 25-hydroxyvitamin D level was 27 nmol/L. 25-Hydroxyvitamin D levels rose in the vitamin D group relative to the placebo group by 4 weeks (16 nmol/L, 95% CI 11 to 21, p < 0.001). There was no improvement in flow-mediated dilatation in the vitamin D group relative to placebo at 4 weeks (0.1%, 95% CI -0.9 to 1.1, p = 0.84) or 8 weeks (0.0%, 95% CI -1.4 to 1.4, p = 0.98). There was no improvement in cholesterol, insulin resistance or markers of inflammation. Both platelet activation inhibitor-1 and tissue plasminogen activator levels fell significantly in the vitamin D group relative to placebo at 8 weeks. CONCLUSION: A single large dose of vitamin D3 did not improve blood pressure or endothelial function in South Asian women with low baseline 25-hydroxyvitamin D levels. TRIAL REGISTRATION: ISRCTN75081811.

Phosphate: the new cholesterol? The role of the phosphate axis in non-uremic vascular disease.

Higher serum phosphate levels within the normal range are associated with substantially increased risk of cardiovascular disease events. Whether this reflects a causative relationship is unknown. Phosphate-responsive hormones (fibroblast growth factor-23, parathyroid hormone and calcitriol) are also predictors of cardiovascular mortality in populations without kidney disease or recognised disturbances of bone mineral metabolism. The high bioavailable phosphate content of Western diets may contribute to this apparent discrepancy between 'normal' and optimal phosphate axis parameters. Although uremic hyperphosphatemia is recognised to cause vascular medial calcification, this does not readily explain the association of higher-normal phosphate with common athero-occlusive phenomena. The phosphate axis may in fact play a role in atherogenesis; observational data link higher levels of phosphate and fibroblast growth factor-23 with coronary atheroma burden, whilst dietary phosphate supplementation accelerates atherosclerosis in a mouse model. In vitro studies show adverse effects of phosphate increases on both vascular smooth muscle cells and endothelium, though these observations have not yet been extended to phosphate increments within the normal range. Receptors for phosphate-responsive hormones are present throughout the cardiovascular system and may mediate atherogenic effects. Since interventions are already available to manipulate the phosphate axis, this is an important issue. If an atherogenic role for phosphate exposure is demonstrated then phosphate binders could become the new statins.

Folic acid supplementation improves vascular function in professional dancers with endothelial dysfunction.

OBJECTIVE: To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. DESIGN: Prospective cross-sectional study. SETTING: Academic institution in the Midwestern United States. SUBJECTS: Twenty-two professional ballet dancers volunteered for this study. MAIN OUTCOME MEASURES: Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flow-induced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. RESULTS: Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). CONCLUSIONS: This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention.

Relationships between vascular calcification, calcium metabolism, bone density, and fractures.

Factors involved with calcium metabolism, such as serum calcium and phosphate and calcium intake, have been associated with vascular disease in different populations. We investigated whether this association is mediated via increased vascular calcification by assessing relationships between these factors and abdominal aortic calcification (AAC) and coronary artery calcification (CAC). A total of 1471 healthy postmenopausal women participated in a 5-year randomized, placebo-controlled trial of calcium 1 g/day, and 323 healthy middle-aged and older men participated in a 2-year randomized, placebo-controlled trial of calcium 600 or 1200 mg/day. AAC was assessed on vertebral morphometric images at baseline and follow-up. Based on computed tomography, 163 men had CAC assessed, on average, 1.5 years after study completion. In elderly women, AAC was positively related to serum calcium (p < .001), phosphate (p = .04), and the calcium-phosphate product (p = .003), but changes in AAC over time and incidence of cardiovascular events were not related to these variables. In middle-aged men, AAC and CAC were not consistently related to these variables. Neither dietary calcium intake nor calcium supplementation was associated with changes in the prevalence of AAC over time, and calcium supplementation also was not related to CAC scores in men. After adjusting for age, AAC was not associated with low bone mineral density (BMD) at baseline, changes in BMD over time, or fracture incidence. CAC also was not related to baseline BMD. In summary, serum calcium and phosphate are associated with AAC in older women, but dietary calcium intake and calcium supplementation were not associated with changes in AAC over 2 to 5 years.

Management of statin-intolerant high-risk patients.

Statins are an essential part of the management of patients at high vascular risk and are generally well-tolerated. However, statin intolerance will be observed more frequently as more stringent low density lipoprotein cholesterol (LDL-C) targets are pursued in an ever increasing number of patients. We review the management options for high-risk patients intolerant to statin treatment. Potential strategies include switching to a different statin, reducing the frequency of statin administration, substituting statins with other LDL-C-lowering agents (e.g. ezetimibe, colesevelam or nicotinic acid) and combining low-dose statin treatment with other lipid-modifying drugs. A limited number of studies specifically assessed statin-intolerant patients and most were small and of short duration. It is therefore difficult to make evidence-based recommendations for the management of this population. In addition, all treatment options have limitations in terms of safety and/or efficacy.

Homocysteine, vitamin determinants and neurological diseases.

This review focuses on the putative role of hyper-homocysteinemia in the pathogenesis of different diseases affecting the nervous system, including stroke, Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis and amyotrophic lateral sclerosis. However, a firm pathogenic role of homocysteine in these diseases has never been established. Lowering plasma homocysteine levels trough vitamin therapy failed to prevent vascular diseases. Conversely, normalization of hyper-homocysteinemia caused improvement in patients with cognitive impairment. B vitamin deficiency is the main determinant of homocysteine levels. However, it has been hypothesized that homocysteine might be a mere marker of vitamin deficiency or an indicator of disease rather than a risk factor. A more consistent use of thresholds to define deficiency is needed to recommend routine screening, monitoring and supplementation of B vitamins to ameliorate the prognosis of the above mentioned disorders. To date, data are insufficient to firmly establish which one of the hypotheses made is correct and the question concerning the real meaning of hyper-homocysteinemia in the pathology of the nervous system still remains an intriguing medical dilemma.

Intake of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol in relation to vascular inflammation and endothelial dysfunction in middle age-elderly men and post-menopausal women living in Northern Italy.

BACKGROUND AND AIMS: It has been suggested that lignan intake may decrease the risk for cardiovascular disease (CVD) by modifying traditional risk factors as well as aortic stiffness. However, the role of dietary lignans on the vascular system is largely unknown. The objective was to investigate whether dietary intake of plant lignans in a free-living population was associated with markers of vascular inflammation and function. METHODS AND RESULTS: We performed a cross-sectional study in 242 (151 males) men and post-menopausal women. Anthropometric characteristics and lignan intake were evaluated. Soluble intercellular adhesion molecule-1 (sICAM-1), insulin, high-sensitive C-reactive protein, glucose, total cholesterol, HDL-cholesterol and triacylglycerols were measured in fasting blood samples. Brachial flow-mediated dilation (FMD) measurements were available for 101 subjects (56 males). Median (interquartile range) daily intake of matairesinol (MAT), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol (LARI), and total lignans was 20.9 microg (17.4), 335.3 microg (289.1), 96.7 microg (91.1), 175.7 microg (135.8), and 665.5 microg (413.7), respectively, as assessed by 3-day weighed food record. Plasma concentrations of sICAM-1 (whole sample) significantly decreased (mean (95%CI) = 358 microg/L (320-401), 276 microg/L (252-303), 298 microg/L (271-326), and 269 microg/L (239-303), P per trend 0.013) and FMD values (FMD sub-group) significantly increased (4.1% (2.2-6.0), 5.7% (4.3-7.2), 6.4% (4.9-7.8), and 8.1% (6.3-10.0), P per trend 0.016) across quartiles of energy-adjusted MAT intake, even after adjustment for relevant clinical and dietary variables. Intake of SECO was also inversely related to plasma sICAM-1 (P per trend 0.018), but not to FMD values. No relationship between intake of PINO, LARI or total lignans and either sICAM-1 or FMD values was observed. CONCLUSIONS: Higher MAT intakes in the context of a typical Northern Italian diet are associated to lower vascular inflammation and endothelial dysfunction, which could have some implications in CVD prevention.

Phosphate feeding induces arterial medial calcification in uremic mice: role of serum phosphorus, fibroblast growth factor-23, and osteopontin.

Arterial medial calcification is a major complication in patients with chronic kidney disease and is a strong predictor of cardiovascular and all-cause mortality. We sought to determine the role of dietary phosphorus and the severity of uremia on vascular calcification in calcification-prone DBA/2 mice. Severe and moderate uremia was induced by renal ablation of varying magnitudes. Extensive arterial-medial calcification developed only when the uremic mice were placed on a high-phosphate diet. Arterial calcification in the severely uremic mice fed a high-phosphate diet was significantly associated with hyperphosphatemia. Moderately uremic mice on this diet were not hyperphosphatemic but had a significant rise in their serum levels of fibroblast growth factor 23 (FGF-23) and osteopontin that significantly correlated with arterial medial calcification. Although there was widespread arterial medial calcification, there was no histological evidence of atherosclerosis. At early stages of calcification, the osteochondrogenic markers Runx2 and osteopontin were upregulated, but the smooth muscle cell marker SM22alpha decreased in medial cells, as did the number of smooth muscle cells in extensively calcified regions. These findings suggest that phosphate loading and the severity of uremia play critical roles in controlling arterial medial calcification in mice. Further, FGF-23 and osteopontin may be markers and/or inducers of this process.

Vascular factors and depression.

OBJECTIVE: This paper examines possible mechanisms that may explain the bi-directional relationship between vascular disease and depression. DESIGN: A literature review was carried out using Medline from 1996 to 2007, using relevant key words including vascular depression, and supplemented by key references to earlier work. RESULTS: Several mechanisms were considered including: autonomic dysfunction, platelet activation, hypothalamic pituitary axis activation, endothelial dysfunction, cytokines, omega 3 fatty acids, genetics, homocysteine and effects of treatment. CONCLUSIONS: The relationship between vascular disease and depression cannot solely be explained by current established risk factors or the effects of treatment for depression. Other mechanisms must apply, and there is some evidence for common genetic factors. Promising future lines of investigation include homocysteine, cytokines and endothelial dysfunction. More longitudinal studies combined with measurements of these biomarkers are needed.