The Angiotensin Type 2 Receptor In Human Adrenocortical Zona Glomerulosa And In Aldosterone-Producing Adenoma: Low Expression And No Functional Role
The angiotensin II type 2 receptor (AT2R) and the angiotensin-(1-7) receptor (MasR) play a cardiovascular protective role by counter-regulating angiotensin II type 1 receptor (AT1R)-mediated effects, but whether this involves blunting of adrenocortical hormone secretion is unknown. We investigated the presence of AT1R, AT2R and MasR in aldosterone-producing adenoma (APA), a condition featuring hyperaldosteronism, and in APA-adjacent tissue. The effect of C21, an AT2R agonist, on CYP11B1 (cortisol synthase) and CYP11B2 (aldosterone synthase) gene expression in NCI-H295R and HAC15 cell lines, and in APA and APA-adjacent tiss...
Source: Clinical Science - February 7, 2018 Category: Biomedical Science Authors: Vanderriele, P. E., Caroccia, B., Seccia, T. M., Piazza, M., Lenzini, L., Torresan, F., Iacobone, M., Unger, T., Rossi, G. P. Tags: PublishAheadOfPrint Source Type: research
Cyclic stretch-induced Crp3 sensitizes vascular smooth muscle cells to apoptosis during vein arterialization remodeling
Vein graft failure limits the long-term patency of the saphenous vein used as a conduit for coronary artery bypass graft. Early graft adaptation involves some degree of intima hyperplasia to sustain the hemodynamic stress, but the progress to occlusion in some veins remains unclear. We have demonstrated that stretch-induced up-regulation of cysteine and glycine-rich protein 3 (Crp3) in rat jugular vein and human saphenous vein in response to arterialization. Here, we developed a Crp3-KO rat to investigate the role of Crp3 in vascular remodeling. After 28 days jugular vein arterialization, the intima layer was 3-fold thicke...
Source: Clinical Science - February 2, 2018 Category: Biomedical Science Authors: Campos, L. C. G., Ribeiro-Silva, J. C., Menegon, A. S., Barauna, V. G., Miyakawa, A. A., Krieger, J. E. Tags: PublishAheadOfPrint Source Type: research
Metformin attenuates effects of cyclophilin A on macrophages, reduces lipid uptake and secretion of cytokines by repressing decreased AMPK activity
Growing evidence implicates cyclophilin A secreted by vascular wall cells and monocytes as a key mediator in atherosclerosis. Cyclophilin A in addition to its proliferative effects, during hyperglycaemic conditions, increases lipid uptake in macrophages by increasing scavenger receptors on the cell's surface. It also promotes macrophage migration across endothelial cells and conversion of macrophages to foam cells. Given the known effects of metformin in reducing vascular complications of diabetes, we investigated the effect of metformin on cyclophilin A action in macrophages. Using an ex vivo model of cultured macr...
Source: Clinical Science - January 30, 2018 Category: Biomedical Science Authors: Ramachandran, S., Anandan, V., Kutty, V. R., Mullasari, A., Pillai, M. R., Kartha, C. C. Tags: PublishAheadOfPrint Source Type: research
Elevated Vasopressin in Pregnant Mice Induces T Helper Subset Alterations Consistent with Human Preeclampsia
The pathogenesis of preeclampsia, a hypertensive disorder of pregnancy, involves imbalanced T helper (TH) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of arginine vasopressin (AVP)), secretion precedes the development of symptoms in preeclampsia in humans, and infusion of AVP proximal to and throughout gestation is sufficient to initiate cardiovascular and renal phenotypes of preeclampsia in wild-type C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient to induce the immune changes observed in human preeclampsia. AVP ...
Source: Clinical Science - January 25, 2018 Category: Biomedical Science Authors: Scroggins, S. M., Santillan, D. A., Lund, J. M., Sandgren, J. A., Krotz, L. K., Hamilton, W. S., Devor, E. J., Davis, H. A., Pierce, G. L., Gibson-Corley, K. N., Sigmund, C. D., Grobe, J. L., Santillan, M. K. Tags: PublishAheadOfPrint Source Type: research
Gene delivery of medium chain acyl-coenzyme A dehydrogenase (MCAD) induces physiological cardiac hypertrophy and protects against pathological remodelling
We previously showed that medium chain acyl-coenzyme A dehydrogenase (MCAD, key regulator of fatty acid oxidation) is positively modulated in the heart by the cardioprotective kinase, phosphoinositide 3-kinase [PI3K(p110α)]. Disturbances in cardiac metabolism are a feature of heart failure patients, and targeting metabolic defects is considered a potential therapeutic approach. The specific role of MCAD in the adult heart is unknown. To examine the role of MCAD in the heart and to assess the therapeutic potential of increasing MCAD in the failing heart, we developed a gene therapy tool using recombinant adeno-associa...
Source: Clinical Science - January 22, 2018 Category: Biomedical Science Authors: Bernardo, B. C., Weeks, K. L., Pongsukwechkul, T., Gao, X., Kiriazis, H., Cemerlang, N., Boey, E. J., Tham, Y. K., Johnson, C. J., Qian, H., Du, X.-J., Gregorevic, P., McMullen, J. R. Tags: PublishAheadOfPrint Source Type: research
Blockade of histone deacetylase 6 protects against cisplatin-induced acute kidney injury
In this study, we utilized a murine model of cisplatin-induced acute kidney injury (AKI) and a highly selective inhibitor of HDAC6, tubastatin A (TA), to assess the role of HDAC6 in nephrotoxicity and its associated mechanisms. Cisplatin-induced AKI was accompanied by increased expression and activation of HDAC6; blocking HDAC6 with TA lessened renal dysfunction, attenuated renal pathological changes, reduced expression of neutrophil gelatinase-associated lipocalin and Kim-1, and decreased tubular cell apoptosis. In cultured human epithelial cells, TA or HDAC6 siRNA treatment also inhibited cisplatin-induced apoptosis. Mec...
Source: Clinical Science - January 22, 2018 Category: Biomedical Science Authors: Tang, J., Shi, Y., Liu, N., Xu, L., Zang, X., Li, P., Zhang, J., Zheng, X., Qiu, A., Zhuang, S. Tags: PublishAheadOfPrint Source Type: research
Rapamycin activates TGF receptor independently of its ligand: implications for endothelial dysfunction
In conclusion, we provide evidence that rapamycin activates TGF receptor independent of its ligand TGFb, in concert with promotion of PAI-1 expression and changes in endothelial phenotype. These undesirable effects, the prothrombogenic state and activation of EndMT, are SMAD2-dependent and independent of the therapeutic rapamycin-induced cell proliferation arrest. (Source: Clinical Science)
Source: Clinical Science - January 17, 2018 Category: Biomedical Science Authors: Miyakawa, A. A., Girao-Silva, T., Krieger, J. E., Edelman, E. R. Tags: PublishAheadOfPrint Source Type: research
The VEGFA165b isoform is dysregulated in senescent endothelial cells and may be associated with prevalent and incident coronary heart disease
Coronary heart disease (CHD) is a leading cause of morbidity in the over 65s; over 40% of all deaths are due to this condition. The association between increasing age and CHD is well-documented; the accumulation of senescent cells in cardiac and vascular tissues may represent one factor underpinning this observation. We aimed to identify senescence-related expression changes in primary human senescent cardiomyocytes and endothelial cells and to relate transcript expression in peripheral blood leucocytes to prevalent and incident CHD in the InCHIANTI study of aging. We quantified splicing factor expression and splicing patt...
Source: Clinical Science - January 12, 2018 Category: Biomedical Science Authors: Latorre, E., Pilling, L. C., Lee, B. P., Bandinelli, S., Melzer, D., Ferrucci, L., Harries, L. W. Tags: PublishAheadOfPrint Source Type: research
Non-uniform relationship between salt status and aldosterone activity in patients with chronic kidney disease
Discussion: We demonstrate dysregulation of aldosterone in CKD in response to salt loading with intravenous saline, but not to dietary salt modification. (Source: Clinical Science)
Source: Clinical Science - January 10, 2018 Category: Biomedical Science Authors: Taylor, A. H. M., Rankin, A. J., McQuarrie, E. P., Freel, E. M., Homer, N. Z. M., Andrew, R., Jardine, A. G., Mark, P. B. Tags: PublishAheadOfPrint Source Type: research
Impaired contraction of blood clots as a novel prothrombotic mechanism in systemic lupus erythematosus
In conclusion, autoantibodies in SLE can affect platelet contractility, resulting in reduced ability of clots and thrombi to shrink in volume, which increases vessel obstruction and may aggravate the course and outcomes of thrombotic complications in SLE. (Source: Clinical Science)
Source: Clinical Science - January 2, 2018 Category: Biomedical Science Authors: Le Minh, G., Peshkova, A. D., Andrianova, I. A., Sibgatullin, T. B., Maksudova, A. N., Weisel, J. W., Litvinov, R. Tags: PublishAheadOfPrint Source Type: research
Independent and combined effects of airway remodelling and allergy on airway responsiveness
This study investigated the separate and combined effects of increased airway smooth muscle (ASM) layer thickness and allergy on airway hyperresponsiveness. We integrated a protocol of ovalbumin (OVA)-induced allergy into a non-inflammatory mouse model of ASM remodelling induced by conditional and airway-specific expression of TGF-α in Egr-1 deficient transgenic mice, which produced thickening of the ASM layer following ingestion of doxycycline. Mice were sensitised to OVA and assigned to one of four treatment groups: Allergy - normal chow diet and OVA challenge; Remodelling - doxycycline in chow and saline challenge...
Source: Clinical Science - December 21, 2017 Category: Biomedical Science Authors: Wang, K. C., Le Cras, T. D., Larcombe, A. N., Zosky, G. R., Elliot, J. G., James, A. L., Noble, P. B. Tags: PublishAheadOfPrint Source Type: research
Functional Blocking of Ninjurin1 as a Strategy for Protecting Endothelial Cells in Diabetes Mellitus
Ongoing efforts to remove pathological inflammatory stimuli are crucial for the protection of endothelial cells in diabetes. Nerve injury-induced protein 1 (Ninj1) is an adhesion molecule that not only contributes to inflammation but also regulates the apoptosis of endothelial cells. In the present study, Ninj1 was found highly expressed in endothelial cells in type 2 diabetic mice and increased in high-glucose (HG) cultured HUVECs. Furthermore, we found that Ninj1 levels are up-regulated in endothelial cells in clinical specimens of diabetic patients when compared with non-diabetic tissues, indicating a biological correla...
Source: Clinical Science - December 20, 2017 Category: Biomedical Science Authors: Wang, X., Qin, J., Zhang, X., Peng, Z., Ye, K., Wu, X., Yang, X., Shi, H., Zhao, Z., Guo, X., Liu, X., Yin, M., Lu, X. Tags: PublishAheadOfPrint Source Type: research
Fetal growth restriction in mice modifies postnatal airway responsiveness in an age and sex-dependent manner
Epidemiological studies demonstrate an association between intrauterine growth restriction (IUGR) and asthma, however the underlying mechanism is unknown. We investigated the impact of maternal hypoxia-induced IUGR on airway responsiveness in male and female mice during juvenility and adulthood. Pregnant BALB/c mice were housed under hypoxic conditions for gestational days 11-17.5 and then returned to normoxic conditions for the remainder of pregnancy. A control group were housed under normoxic conditions throughout pregnancy. Offspring were studied at 2 weeks (juveniles) and 8 weeks (adults), where lung volume was assesse...
Source: Clinical Science - December 20, 2017 Category: Biomedical Science Authors: Wang, K. C. W., Larcombe, A. N., Berry, L. J., Morton, J. S., Davidge, S. T., James, A. L., Noble, P. B. Tags: PublishAheadOfPrint Source Type: research
Dual {alpha}v{beta}3 And {alpha}v{beta}5 Blockade Attenuates Fibrotic And Vascular Alterations In A Murine Model Of Systemic Sclerosis
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibroblast activation and fibrosis of the skin and internal organs. Alterations in cell-integrin interaction are sufficient to initiate pro-fibrotic processes. SSc fibroblasts express both αvβ3 and αvβ5 integrins and their activation induces myofibroblasts differentiation. The aim of this study was to evaluate the effect of the anb3 and anb5 inhibitor, cilengitide, on the development of vascular and fibrotic changes in the chronic oxidant stress murine model of systemic sclerosis. SSc was induced in BALB/c mice by daily s.c. inj...
Source: Clinical Science - December 13, 2017 Category: Biomedical Science Authors: Bagnato, G., Irrera, N., Pizzino, G., Santoro, D., Roberts, W. N., Bagnato, G., Pallio, G., Vaccaro, M., Squadrito, F., Saitta, A., Altavilla, D., Bitto, A. Tags: PublishAheadOfPrint Source Type: research
Intracranial pulsatility in patients with cerebral small vessel disease: a systematic review
In conclusion, most studies support a cross-sectional association between higher pulsatility in large intracranial arteries and SVD. Future studies should minimise bias, adjust for potential confounders, include pulsatility in veins and CSF, and examine longitudinal relationship between pulsatility and SVD. Agreement on reliable measures of intracranial pulsatility would be helpful. (Source: Clinical Science)
Source: Clinical Science - December 11, 2017 Category: Biomedical Science Authors: Shi, Y., Thrippleton, M. J., Marshall, I., Wardlaw, J. M. Tags: PublishAheadOfPrint Source Type: research
