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Total 48 results found since Jan 2013.
Abstract P310: Atuplex Formulated With Small Interfering RNA For Soluble Fms-like Tyrosine Kinase-1 (sFLT1) Selectively Silences Maternal And Placental sFLT1 In A Preeclamptic Rat Model Session Title: Pregnancy and Preeclampsia and Developmental Programming of Cardiovascular Disease
Preeclampsia is a pregnancy-related disorder characterized by hypertension and proteinuria, affecting about 5-8% of pregnancies. It is a major cause of fetal and maternal morbidity/mortality. The disease is most probably multifactorial and caused by several placental dysfunctions. As an important mediator, sFLT1 is induced in the placenta and in the serum of preeclamptic women, acting as a decoy receptor for placenta like growth factors (PLGF) and inducing an antiangiogenic balance. RNAi mediated gene specific silencing could represent a new therapeutic option in preeclampsia management. We tested sFLT1-specific small inte...
Source: Hypertension - September 14, 2017 Category: Cardiology Authors: Nadine Haase, Kristin Kraker, Ute Schaeper, Jens Endruschat, Dominik N Muller, Ralf Dechend Tags: Poster Abstract Presentations Source Type: research
Estrogen Receptor-{beta} in the Paraventricular Nucleus and Rostroventrolateral Medulla Plays an Essential Protective Role in Aldosterone/Salt-Induced Hypertension in Female Rats Estrogen
The identification of the specific estrogen receptor (ER) subtypes that are involved in estrogen protection from hypertension and their specific locations in the central nervous system is critical to our understanding and design of effective estrogen replacement therapies in women. Using selective ER agonists and recombinant adeno-associated virus (AAV) carrying small interference (si) RNA to silence either ERα (AAV-siRNA-ERα) or ERβ (AAV-siRNA-ERβ), the present study investigated regional specificity of different ER subtypes in the protective actions of estrogen in aldosterone (Aldo)-induced hyperten...
Source: Hypertension - May 15, 2013 Category: Cardiology Authors: Xue, B., Zhang, Z., Beltz, T. G., Johnson, R. F., Guo, F., Hay, M., Johnson, A. K. Tags: Animal models of human disease, Other hypertension Estrogen Source Type: research
Abstract P192: Both Mineralocorticoid Receptor and Angiotensin II type 1 Receptors in the Subfornical Organ Mediate Angiotensin II Induced Reactive Oxygen Species (ROS) in Brain Angiotensinergic Pathways Session Title: Neurogenic Mechanisms
Activation of angiotensinergic pathways and central aldosterone (aldo)-MR-ENaC-endogenous ouabain (EO)-AT1R pathway play a critical role in Ang II associated hypertension. The SFO contains both MR and AT1R and can relay the signals of circulating Ang II to downstream nuclei such as the PVN, SON and RVLM. We evaluated the effect of knockdown of MR and AT1R specific in the SFO on reactive oxygen species (ROS) production in downstream nuclei. Wistar rats were intra SFO infused with AAV-MR- or AT1aR-siRNA and after 7 days received a sc infusion of Ang II at 500 ng/min/kg for 2 weeks. MR and AT1R expression were measured by rea...
Source: Hypertension - November 3, 2015 Category: Cardiology Authors: Wang, H.-W., White, R., Huang, B. S., Chen, A., Ahmad, M., Leenen, F. H. Tags: Session Title: Neurogenic Mechanisms Source Type: research
Abstract 154: Knockdown of Mineralocorticoid or AT1 Receptor Gene in the Paraventricular Nucleus Prevents Ang II Induced Hypertension in Rats Poster Session I
Circulating Ang II activates an aldosterone-MR-AT1R pathway in the hypothalamus. To obtain insights into the actual aldosterone-MR- AT1R neuronal pathway, the present study examined whether intra-PVN infusion of AAV-AT1aR-siRNA or AAV-MR-siRNA prevents the Ang II induced increases in AT1R and MR expression and BP. Two weeks sc infusion of Ang II at 500ng/kg/min in Wistar rats on regular salt diet increased BP by telemetry by 66 ± 3 mm Hg, and AT1R and MR protein in the SFO, SON and PVN. Intra-PVN AT1aR-siRNA decreased AT1R but not MR expression in the PVN by sc Ang II, and MR-siRNA decreased MR but not AT1R expressi...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Chen, A., Huang, B. S., Wang, H., Ahmad, M., Leenen, F. H. Tags: Poster Session I Source Type: research
Abstract 161: The (Pro)renin Receptor Regulates Renin Release and Prorenin-to-Renin Conversion in (Pro)Renin-Synthesizing Human Mast Cells Poster Session I
In conclusion, (P)RR knockdown affects both prorenin-renin conversion and (pro)renin release, resulting in a net rise of the renin/prorenin ratio in the medium.
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Lu, X., Krop, M., Garrelds, I. M., van Gool, J. M., Jan Danser, A. H. Tags: Poster Session I Source Type: research
Abstract 275: Tissue Transglutaminase Stabilizes Placental AT1 Receptor and Contributes to Pathophysiology in Preeclampsia Poster Session I
Preeclampsia (PE) is a serious hypertensive disease of pregnancy associated with the presence of the major angiotensin receptor AT1-agnostic autoantibodies (AT1-AAs) that cause the defining PE features when introduced into pregnant mice. To understand AT1-AA-mediated receptor activation in PE, we explored the role of tissue transglutaminases (TG2), the most ubiquitous member of a group of enzymes modifying proteins by catalyzing the formation of -(-glutamyl)-lysine isopeptide bonds. TG2, a versatile protein that can also function as a G protein, is enriched in the syncytiotrophoblasts of placenta, the key organ in PE patho...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Liu, C., Wang, W., Parchim, N., Irani, R., Ning, C., Sun, K., Zhao, S., Zhao, C., Song, A., Zhang, Y., Blackwell, S., Sibai, B., Jin, J., Kellems, R., Xia, Y. Tags: Poster Session I Source Type: research
Abstract 280: Sflt-1 is Regulated via Both Transcriptional and Post-transcriptional Modification in Preeclampsia Poster Session I
Preeclampsia (PE) is a life-threatening hypertensive renal disorder of pregnancy. Soluble fms-like tyrosine kinase 1 (sFlt-1), an anti-angiogenic factor, is elevated and contributes to PE. However, molecular basis underlying its up-regulation in PE remains unclear. Here we report that hypoxia inducible factor-1α (HIF-1α), an important transcriptional factor, and U2AF65, a key molecule involved in alternative splicing, are significantly increased in the placentasof PE patients compared to the controls. Using two animal models of PE including angiotensin receptor type 1 receptor agonistic autoantibody (AT1-AA) an...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Wang, W., Parchim, N., Iriyama, T., Luo, R., Zhao, C., Zhang, Y., Blackwell, S., Sabai, B., Tao, L., Kellems, R., Xia, Y. Tags: Poster Session I Source Type: research
Abstract P099: Angiotensin Type I Receptor (AT1R) and (Pro)renin Receptor (PRR) Functional Heterodimer Mediates ERK Phosphorylation Session Title: Poster Session 1- Trainee Onsite Poster Competition and Reception
Receptor dimerization was shown to enhance the receptor efficacy, trafficking and signal transduction. Angiotensin II type 1 receptor (AT1R) and (Pro)renin receptor (PRR) are expressed in the kidney. Studies demonstrated that these two receptors have some similarities in their signaling mechanisms and effects. In the present study we hypothesized that the AT1R and PRR form functional heterodimer to enhance cellular ERK phosphorylation. Using Immunoprecipitation technique, confocal immunofluorescence staining (IF), and fluorescence resonance energy transfer (FRET), we evaluated the presence of AT1R and PRR heterodimer in ra...
Source: Hypertension - November 3, 2015 Category: Cardiology Authors: Quadri, S. S. A., Li, C., Culver, S., Siragy, H. M. Tags: Session Title: Poster Session 1- Trainee Onsite Poster Competition and Reception Source Type: research
Abstract P141: Cardiac TRH Partly Mediates Angiotensin II-induced Fibrotic and Hypertrophy Effects in "in vivo" and "in vitro" Models Session Title: Angiotensin Action and Signaling/Renin Angiotensin System 1
Cardiac TRH (cTRH) is overexpressed in the hypertrophied ventricle (LV) of the SHR. Additionally in vivo siRNA-TRH treatment induced downregulation of LV-TRH preventing cardiac hypertrophy and fibrosis demonstrating that TRH is involved in hypertrophic and fibrotic processes. Moreover, in a normal heart, the increase of LV TRH expression alone could induce structural changes where fibrosis and hypertrophy could be involved, independently of any other system alterations.Is well-known the cardiac hypertrophy/ fibrotic effects induced by AII, raising the question of whether specific LV cTRH inhibition might attenuates AII ind...
Source: Hypertension - November 3, 2015 Category: Cardiology Authors: Garcia, S. I., Peres Diaz, L. S., Aisicovich, M., Schuman, M. L., Landa, M. S. Tags: Session Title: Angiotensin Action and Signaling/Renin Angiotensin System 1 Source Type: research
Abstract 75: Nrf2 Mediates the Antioxidant Effect of D2r Via Dj-1 in the Kidney Oral Session IX: Concurrent B Oxidative Stress
Renal dopamine D2 receptor (D2R) dysfunction is associated with increased oxidative stress and high blood pressure. We have reported that DJ-1 is regulated by D2R in the kidney. Nrf2 is a transcription factor that regulates the expression of several antioxidant genes. We hypothesize that Nrf2 is involved in the DJ-1-mediated regulation of reactive oxygen species (ROS) production in the kidney. DJ-1 and Nrf2 co-inmunoprecipitate in mouse kidney. Selective renal silencing of D2R in mice by the renal subcapsular infusion of D2R siRNA (~50%) decreases Nrf2 expression (63.4%±3.4, n=7, P<0.05), and silencing of D2R exp...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Cuevas, S., Yang, Y., Assico, L., Feranil, J., Jones, J., Armando, I., Jose, P. A. Tags: Oral Session IX: Concurrent B Oxidative Stress Source Type: research
Abstract 191: Transcriptional Regulation of Renin by Nuclear Receptors Co-regulated With Renin Poster Session I
Expression of the renin gene is required to maintain normal morphological and physiological identity of renal juxtaglomerular (JG) cells, yet the mechanisms regulating renin gene transcription remain elusive. We re-examined data from Brunskill et. al (JASN 22:2213, 2011), investigating genome-wide gene expression in JG and other renal cell types. Based on our previous data implicating nuclear receptors (RAR, RXR, VDR, PPARG, Nr2f2 and Nr2f6) in the regulation of mouse and human renin gene expression, we focused our analysis on the expression of genes encoding the 48 nuclear hormone receptors and their co-regulation with re...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Lu, K.-T., Weatherford, E. T., Ketsawatsomkron, P., Grobe, J. L., Sigmund, C. D. Tags: Poster Session I Source Type: research
Abstract 22: Histone Deacetylase (HDAC) 4 Controls Neointimal Hyperplasia via Stimulating Proliferation and Migration of Vascular Smooth Muscle Cells Oral Session II: Concurrent B Vascular Biology
Histone deacetylases (HDACs) are transcriptional co-regulators. We have recently demonstrated that a class IIa HDAC, HDAC4 promotes reactive oxygen species (ROS)-dependent vascular smooth muscle inflammation and mediates the development of hypertension in spontaneously hypertensive rats. Pathogenesis of hypertension is in part modulated by vascular structural remodeling via proliferation and migration of vascular smooth muscle cells (SMCs). We thus examined whether HDAC4 controls SMCs proliferation and migration. In rat mesenteric arterial SMCs, small interfering RNA (siRNA) against HDAC4 inhibited platelet-derived growth ...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Usui, T., Okada, M., Yamawaki, H. Tags: Oral Session II: Concurrent B Vascular Biology Source Type: research
Abstract 52: Human Grk4{gamma}142v, Via Histone Deacetylase 1, Produces At1r-dependent Hypertension Oral Session VII: Concurrent A Clinical Issues
Human gene variants account for only a small proportion of essential hypertension in humans and have not been shown to produce hypertension in transgenic mice. The association between hypertension and 11 allelic variants of 8 candidate genes in humans (n=1074) was studied. We also evaluated the response to angiotensin receptor blockers (ARBs) in humans (n=681) and transgenic mice generated to express the human wild-type G protein-coupled receptor kinase 4 (hGRK4WT) or the 142V allele (hGRK4142V). hGRK4 variants (R65L, A142V, and A486V) were associated with essential hypertension; hGRK4142V, by itself, predicted the hyperte...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Jose, P., Wang, Z., Sanada, H., Yoneda, M., Zheng, C., Williams, S., Bartlett, J., White, M., Gordon, L., Liu, M., Konkalmatt, P., Wang, X., Asico, L., Villar, V. A., Jones, J., Armando, I., Felder, R., Eisner, G. Tags: Oral Session VII: Concurrent A Clinical Issues Source Type: research
Abstract 441: Aldosterone-salt Hypertension Depends on the SFO, Central Aldosterone Synthase and MR Specifically in the PVN Poster Session II
We examined the role of the subfornical organ (SFO), aldo synthesized locally in the brain, and MR specifically in the paraventricular nucleus (PVN) in aldo-salt hypertension. Wistar rats with telemetry probes were treated with chronic intra-cerebroventricular infusion of aldo synthase (AS) inhibitor FAD286 (25 μg/day), MR blocker eplerenone (5 μg/day) or vehicle. After 2 days, subcutaneous (sc) aldo infusion (1 μg/h) was started and saline was provided as drinking water. In a second set of rats with telemetry, electrolytic or sham lesions of the SFO, or bilateral intra-PVN infusion of AAV-MR-siRNA or AAV-SCM-siRN...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Huang, B. S., Ahmad, M., Chen, A., White, R. A., Leenen, F. H., Leenen, F. H. Tags: Poster Session II Source Type: research
Abstract P086: Superoxide but Not Hydrogen Peroxide Increases Nuclear Translocation of Transcription Factor Sp3 and AT1 Receptor Expression in the Renal Cells Session Title: Poster Session 1- Trainee Onsite Poster Competition and Reception
Age-associated oxidative stress causes up-regulation of renal AT1 receptor function (AT1R) and hypertension in aging Fischer Brown Norway (FBN) rats. Here we studied the mechanism of up-regulation of renal AT1R, and further tested superoxide Vs hydrogen peroxide (H2O2) specificity in this phenomenon. We found that transcription factor Sp3 plasmid increased (Control vs Sp3: 0.1165 ± 0.01 vs 0.3810 ± 0.03) while Sp3 siRNA decreased (Control siRNA vs Sp3 siRNA: 1.11 ± 0.25 vs 0.64 ± 0.06) the levels of AT1 receptor protein in human kidney (HK2) cells. Whereas transcription factor NF-kB p-65 plasmid...
Source: Hypertension - November 3, 2015 Category: Cardiology Authors: Saleem, M. Tags: Session Title: Poster Session 1- Trainee Onsite Poster Competition and Reception Source Type: research
