Loss of microRNA-22 prevents high fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy
In this study, we examined the role of miR-22 in the cardiac and metabolic alterations promoted by high fat (HF) diet. We found that loss of miR-22 attenuated the gain of fat mass and prevented dyslipidemia induced by HF diet, although the body weight gain, or glucose intolerance and insulin resistance did not seem to be affected. Mechanistically, loss of miR-22 attenuated the increased expression of genes involved in lipogenesis and inflammation mediated by HF diet. Similarly, we found that miR-22 mediates metabolic alterations and inflammation induced by obesity in the liver. However, loss of miR-22 did not appear to alt...
Source: Clinical Science - November 3, 2017 Category: Biomedical Science Authors: Diniz, G. P., Huang, Z.-P., Liu, J., Chen, J., Ding, J., Fonseca, R. I., Barreto-Chaves, M. L., Donato, J., Hu, X., Wang, D.-Z. Tags: PublishAheadOfPrint Source Type: research
Autoantibodies against AT1 and {alpha}1-Adrenergic Receptors Predict Arterial Stiffness Progression in Normotensive Subjects Over a 5-Year Period
Conclusion: We have shown for the first time that the type of AT1-AAs and α1-AAs are independent predictors for aortic stiffness progression in normotensive subjects. Our data collectively support the utility of these autoantibodies as potential markers of aortic stiffness. (Source: Clinical Science)
Source: Clinical Science - November 2, 2017 Category: Biomedical Science Authors: Li, G., Cao, Z., Wu, X.-w., Wu, H.-k., Ma, Y., Wu, B., Wang, W.-q., Cheng, J., Zhou, Z.-h., Tu, Y.-c. Tags: PublishAheadOfPrint Source Type: research
GLP-1 response to sequential mixed meals: influence of insulin resistance.
Previous work has shown that potentiation of insulin release is impaired in non-diabetic insulin resistance; we tested the hypothesis that this defect may be related to altered GLP-1 release. On consecutive days, 82 non-diabetic individuals, classified as insulin sensitive (IS, n=41) or insulin resistant (IR, n=41) by euglycaemic clamp, were given two sequential mixed meals with standard (75 g, LCD) or double (150 g, HCD) carbohydrate content. Plasma glucose, insulin, C-peptide, NEFA and GLP-1 concentrations were measured; β-cell function (glucose sensitivity and potentiation) was resolved by mathematical modelling. F...
Source: Clinical Science - November 2, 2017 Category: Biomedical Science Authors: Rebelos, E., Astiarraga, B., Bizzotto, R., Mari, A., Manca, M. L., Gonzalez, A., Mendez, A., Martinez, C. A., Hurwitz, B. E., Ferrannini, E. Tags: PublishAheadOfPrint Source Type: research
Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin.
This study investigated the interplay of these factors on junctional occupancy of VE-cadherin and macromolecular leakage in human endothelial monolayers and the perfused placental microvascular bed. Whilst VEGF-A165a (50 ng/ml) increased endothelial monolayer albumin permeability (p<0.0001), equimolar concentrations of VEGF-A165b (p>0.05) or PlGF (p>0.05) did not. Moreover, VEGF-A165b (100 ng/ml; p<0.001) but not PlGF (100 ng/ml; p>0.05) inhibited VEGF-A165a-induced permeability when added singly. PlGF abolished the VEGF-A165b-induced reduction of VEGF-A165a mediated permeability (p>0.05); PlGF was ...
Source: Clinical Science - October 20, 2017 Category: Biomedical Science Authors: Pang, V., Bates, D. O., Leach, L. Tags: PublishAheadOfPrint Source Type: research
Post-prandial hyperlipidaemia results in systemic nitrosative stress and impaired cerebrovascular function in the aged
Post-prandial hyperlipidaemia (PPH) acutely impairs systemic vascular endothelial function, potentially attributable to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability (oxidative-nitrosative stress). However, it remains to be determined whether this extends to the cerebrovasculature. To examine this, 38 (19 young (≤ 35 years) and 19 aged (≥ 60 years)) healthy males were recruited. Cerebrovascular function (middle cerebral artery velocity, MCAv) and cerebrovascular reactivity to hypercapnea (CVRCO2Hyper) and hypocapnea (CVRCO2Hypo) were determined via trans-cranial Doppler ultrasound an...
Source: Clinical Science - October 20, 2017 Category: Biomedical Science Authors: Marley, C. J., Hodson, D., Brugniaux, J. V., Fall, L., Bailey, D. M. Tags: PublishAheadOfPrint Source Type: research
Natural Killer Cells Mediate Pathophysiology in Response to Reduced Uterine Perfusion Pressure
Preeclampsia is associated with hypertension, small-for-gestational-age babies and increased cytolytic natural killer (NK) cells. The specific role of cytolytic NK cells in the pathophysiology of preeclampsia has not been clearly defined. We hypothesized that Reduced Uterine Perfusion Pressure (RUPP) stimulates proliferation and cytolytic activation of NK cells, and that reducing NK cells in RUPP would prevent hypertension, intrauterine growth restriction, and inflammation in response to placental ischemia. RUPP was induced on gestation day (GD) 14 in pregnant rats. NK cells were depleted by i.p. administration of anti-asi...
Source: Clinical Science - October 17, 2017 Category: Biomedical Science Authors: Elfarra, J., Amaral, L. M., McCalmon, M., Scott, J. D., Cunningham, M. W., Gnam, A., Ibrahim, T., LaMarca, B., Cornelius, D. C. Tags: PublishAheadOfPrint Source Type: research
Alterations in Endothelin Type B Receptor Contribute to Microvascular Dysfunction in Women Who Have Had Preeclampsia
Microvascular dysfunction originating during a preeclamptic pregnancy persists postpartum and likely contributes to increased CVD risk in these women. One putative mechanism contributing to this dysfunction is increased vasoconstrictor sensitivity to endothelin-1 (ET-1), mediated by alterations in ET-1 receptor type-B (ETBR). We evaluated ET-1 sensitivity, ETAR and ETBR contributions to ET-1-mediated constriction, and the mechanistic role of ETBR in endothelium-dependent dilation in vivo in the microvasculature of postpartum women who had preeclampsia (PrEC, n=12) and control women who had a healthy pregnancy (HC, ...
Source: Clinical Science - October 17, 2017 Category: Biomedical Science Authors: Stanhewicz, A. E., Jandu, S., Santhanam, L., Alexander, L. M. Tags: PublishAheadOfPrint Source Type: research
The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain
Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial basement membranes of arteries. This project tested the hypotheses that pial-glial basement membranes of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF. The in vivo MRI and PET images were obtained from a 4.2 year old dog, whereas the post-mortem electron microscopy wa...
Source: Clinical Science - October 11, 2017 Category: Biomedical Science Authors: Dobson, H., MacGregor Sharp, M., Cumpsty, R., Criswell, T. P., Wellman, T., Finucane, C., Sullivan, J. M., Weller, R. O., Verma, A., Carare, R. O. Tags: PublishAheadOfPrint Source Type: research
Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decrease elastase-induced AAA development.
In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. (Source: Clinical Science)
Source: Clinical Science - October 5, 2017 Category: Biomedical Science Authors: Fernandez-Garcia, C.-E., Tarin, C., Roldan-Montero, R., Martinez-Lopez, D., Torres-Fonseca, M., Lindhot, J. S., Vega de Ceniga, M., Egido, J., Lopez de Andres, N., Blanco-Colio, L.-M., Martin-Ventura, J.-L. Tags: PublishAheadOfPrint Source Type: research
The structure of the perivascular compartment in the old canine brain: a case study
Dilatation of periarteriolar spaces in MRI of the ageing human brains occurs in white matter, basal ganglia and midbrain but not in cerebral cortex. Perivenous collagenous occurs in periventricular but not in subcortical white matter. Here we test the hypotheses that (a) the capacity for dilatation of periarteriolar spaces correlates with the anatomical distribution of leptomeningeal cells coating intracerebral arteries; (b) the regional development of perivenous collagenous in the white matter correlates with the population of intramural cells in the walls of veins. The anatomical distribution of leptomeningeal and intram...
Source: Clinical Science - October 5, 2017 Category: Biomedical Science Authors: Criswell, T. P., MacGregor Sharp, M., Dobson, H., Finucane, C., Weller, R. O., Verma, A., Carare, R. O. Tags: PublishAheadOfPrint Source Type: research
Human skeletal muscle is refractory to the anabolic effects of leucine during the postprandial muscle-full period in older men
Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest leucine boluses shortly after meals may prolong MPS and delay onset of a "muscle-full" state. However, the effects of nutrient "top-ups" in humans, and particularly older adults where deficits exist, have not been explored. We determined the effects of a leucine top-up after essential amino acid (EAA) feeding on anabolic signaling, MPS and muscle energy metabolism in older men. During 13C6-phenylalanine infusion 16 men (~70y) consumed 15g EAA with (n=8, FED+LEU ) or without (n=8, FED ) ...
Source: Clinical Science - October 5, 2017 Category: Biomedical Science Authors: Mitchell, W. K., Phillips, B. E., Hill, I., Greenhaff, P., Lund, J. N., Williams, J. P., Rankin, D., Wilkinson, D. J., Smith, K., Atherton, P. J. Tags: PublishAheadOfPrint Source Type: research
Soluble levels and endogenous vascular gene expression of KLOTHO are related to inflammation in human atherosclerotic disease
Atherosclerosis is a chronic inflammatory disorder affecting the artery wall. Klotho, an anti-aging factor expressed in the vessel wallsthat participates in the maintenance of vascular homeostasis, can be downregulated by inflammation. In this proof-of-concept work we seek to characterize the arterial KLOTHO expression in the vascular wall, as well as the serum concentration of this protein, in a group of patients with clinical atherosclerotic disease. In addition, we aim to analyze the relationship between Klotho and inflammation. Vascular samples were obtained from 27 patients with atherosclerotic disease under an elect...
Source: Clinical Science - September 28, 2017 Category: Biomedical Science Authors: Martin-Nunez, E., Lopez-Castillo, A., Delgado-Molinos, A., Ferri, C., Rodriguez-Ramos, S., Cerro, P., Perez-Delgado, N., Castro, V., Hernandez-Carballo, C., Mora-Fernandez, C., Donate-Correa, J., Navarro-Gonzalez, J. F. Tags: PublishAheadOfPrint Source Type: research
DLX3 promotes bone marrow mesenchymal stem cells proliferation through H19/miR-675 axis
The underlying molecular mechanism of the increased bone mass phenotype in Tricho-dento-osseous (TDO) syndrome remains largely unknown. Our previous study has shown that the TDO point mutation c.533A>G, Q178R in DLX3 could increase bone density in a TDO patient and transgenic mice partially through delaying senescence in bone marrow mesenchymal stem cells (BMSCs). In the present study, we provided a new complementary explanation for TDO syndrome: the DLX3 (Q178R) mutation increased BMSCs proliferation through H19/miR-675 axis. We found that BMSCs derived from the TDO patient (TDO-BMSCs) had stronger proliferation abil...
Source: Clinical Science - September 28, 2017 Category: Biomedical Science Authors: Zhao, N., Zeng, L., Liu, Y., Han, D., Liu, H., Xu, J., Jiang, Y., Li, C., Cai, T., Feng, H., Wang, Y. Tags: PublishAheadOfPrint Source Type: research
Cannabidiol and Palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
Conclusion: PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy. (Source: Clinical Science)
Source: Clinical Science - September 27, 2017 Category: Biomedical Science Authors: Couch, D. G., Tasker, C., Theophilidou, E., Lund, J. N., O'Sullivan, S. E. Tags: PublishAheadOfPrint Source Type: research
Intake of chocolate liquor increases vascular lesions in apoE-knockout mice
Cocoa polyphenols are thought to reduce the risk of cardiovascular diseases. Thus, cocoa-containing foods may have significant health benefits. Here, we studied the impact of chocolate liquor on vascular lesion development and plaque composition in a mouse model of atherosclerosis. Apolipoprotein E (apoE)-knockout mice were assigned to two groups and fed a Western diet that contained 250 g/kg of either chocolate liquor or a polyphenol-free isoenergetic control paste for 16 weeks. In addition to fat, protein and fibers, the chocolate liquor contained 2 g/kg of polyphenols. Compared to the control group, mice fed the chocola...
Source: Clinical Science - September 25, 2017 Category: Biomedical Science Authors: Yazdekhasti, N., Brandsch, C., Hirche, F., Kuhn, J., Schloesser, A., Esatbeyoglu, T., Huebbe, P., Wolffram, S., Rimbach, G., Stangl, G. I. Tags: PublishAheadOfPrint Source Type: research
