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https://www.readbyqxmd.com/read/27922338/pathophysiology-of-aortic-aneurysm-insights-from-human-genetics-and-mouse-models
#1
Nicole K Wilson, Russell A Gould, Elena Gallo MacFarlane, Mibava Leducq Consortium
Aneurysms are local dilations of an artery that predispose the vessel to sudden rupture. They are often asymptomatic and undiagnosed, resulting in a high mortality rate. The predisposition to develop thoracic aortic aneurysms is often genetically inherited and associated with syndromes affecting connective tissue homeostasis. This review discusses how elucidation of the genetic causes of syndromic forms of thoracic aortic aneurysm has helped identify pathways that contribute to disease progression, including those activated by TGF-β, angiotensin II and Notch ligands...
December 6, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27921041/signaling-crosstalk-between-tubular-epithelial-cells-and-interstitial-fibroblasts-after-kidney-injury
#2
REVIEW
Roderick J Tan, Dong Zhou, Youhua Liu
BACKGROUND: A wide variety of kidney diseases ultimately lead to tubulointerstitial damage. The initial site of injury is usually the renal tubules, with activation of fibroblasts occurring later. Self-limited disease is characterized by transient cellular activation with timed deactivation and ultimately a return to normal functioning, whereas sustained responses characterize chronic disease and the development of irreversible fibrosis. The underlying molecular and cellular mechanisms of this cascade of events remain an area of active research...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27920497/efficacy-and-safety-of-two-fixed-dose-combinations-of-s-amlodipine-and-telmisartan-ckd-828-versus-s-amlodipine-monotherapy-in-patients-with-hypertension-inadequately-controlled-using-s-amlodipine-monotherapy-an-8-week-multicenter-randomized-double-blind-phase
#3
Sang-Hyun Ihm, Hui-Kyung Jeon, Tae-Joon Cha, Taek-Jong Hong, Sang-Hyun Kim, Nae-Hee Lee, Jung Han Yoon, Namsik Yoon, Kyung-Kuk Hwang, Sang-Ho Jo, Ho-Joong Youn
PURPOSE: To evaluate the blood pressure (BP) lowering efficacy and safety of CKD-828, a fixed-dose combination of S-amlodipine (the more active isomer of amlodipine besylate, which is calcium channel blocker) and telmisartan (long acting angiotensin receptor blocker), in patients with hypertension inadequately controlled with S-amlodipine monotherapy. PATIENTS AND METHODS: Eligible patients (N=187) who failed to respond after 4-week S-amlodipine 2.5 mg monotherapy (sitting diastolic blood pressure [sitDBP] ≥90 mmHg) to receive CKD-828 2...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27919636/adrenomedullin-and-angiotensin-ii-signaling-pathways-involved-in-the-effects-on-cerebellar-antioxidant-enzymes-activity
#4
Figueira Leticia, Israel Anita
Human adrenomedullin (AM) is a 52-amino acid peptide involved in cardiovascular control. AM has two specific receptors formed by the calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP) 2 or 3, known as AM1 and AM2 receptors, respectively. In addition, AM has appreciable affinity for the calcitonin gene-1 related peptide receptor (CGRP1), composed of CRLR/RAMP1. In brain, AM and their receptors are expressed in several localized areas, including the cerebellum. AM has been reported as an antioxidant...
December 2, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27919443/importance-of-endogenous-compensatory-vasoactive-peptides-in-broadening-the-effects-of-inhibitors-of-the-renin-angiotensin-system-for-the-treatment-of-heart-failure
#5
REVIEW
Milton Packer, John J V McMurray
The magnitude of the clinical benefits produced by inhibitors of the renin-angiotensin system in heart failure has been modest, possibly because of the ability of renin-angiotensin activity to escape from suppression during long-term treatment. Efforts to intensify pharmacological blockade by use of dual inhibitors that interfere with the renin-angiotensin system at multiple sites have not yielded consistent incremental clinical benefits, but have been associated with serious adverse reactions. By contrast, potentiation of endogenous compensatory vasoactive peptides can act to enhance the survival effects of inhibitors of the renin-angiotensin system, as evidenced by trials that have compared angiotensin-converting enzyme inhibitors with drugs that inhibit both the renin-angiotensin system and neprilysin...
December 2, 2016: Lancet
https://www.readbyqxmd.com/read/27919004/irbesartan-ameliorates-hyperlipidemia-and-liver-steatosis-in-type-2-diabetic-db-db-mice-via-stimulating-ppar-%C3%AE-ampk-akt-mtor-signaling-and-autophagy
#6
Juan Zhong, Wangqiu Gong, Lu Lu, Jing Chen, Zibin Lu, HongYu Li, Wenting Liu, Yangyang Liu, Mingqing Wang, Rong Hu, Haibo Long, Lianbo Wei
Irbesartan (Irb), a unique subset of angiotensin II receptor blockers (ARBs) with PPAR-γ activation function, has been reported to play a role in renal dysfunction, glucose metabolism, and abnormal lipid profile in diabetic animal models and humans. However, the underlying mechanisms that improve hyperlipidemia and liver steatosis are unclear. This study investigated the effects of Irb on lipid metabolism and hepatic steatosis using the spontaneous type 2 diabetic db/db mouse model. The results demonstrated body and liver weight, food consumption, lipid content in serum and liver tissue, and liver dysfunction as well as hepatic steatosis were increased in db/db mice compared with db/m mice, whereas the increases were reversed by Irb treatment...
December 2, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27917469/association-of-dysfunctional-synapse-defective-1-syde1-with-restricted-fetal-growth-syde1-regulates-placental-cell-migration-and-invasion
#7
Hsiao-Fan Lo, Ching-Yen Tsai, Chie-Pein Chen, Liang-Jie Wang, Yun-Shien Lee, Chia-Yu Chen, Chung-Tiang Liang, Mei-Leng Cheong, Hungwen Chen
The transcription factor glial cells missing 1 (GCM1) regulates trophoblast differentiation and function during placentation. Decreased GCM1 expression is associated with preeclampsia, suggesting that abnormal expression of GCM1 target genes may contribute to the pathogenesis of pregnancy complications. Here we identified a novel GCM1 target gene, synapse defective 1 (SYDE1), which encodes a RhoGAP that is highly expressed in human placenta, and demonstrated that SYDE1 promotes cytoskeletal remodelling and cell migration and invasion...
December 5, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27917265/novel-non-invasive-biological-predictive-index-for-liver-fibrosis-in-hepatitis-c-virus-genotype-4-patients
#8
Mahmoud Khattab, Mohamed Amin Sakr, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ashraf Breedy, Mona Fathi, Salwa Gaber, Ahmed Altaweil, Ashraf Osman, Ahmed Hassouna, Ibrahim Motawea
AIM: To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. METHODS: A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR)...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27917210/association-of-interleukin-17-angiotensin-ii-with-refractory-hypertension-risk-in-hemodialysis-patients
#9
Zebin Wang, Wei Shi, Xinling Liang, Wenjian Wang, Jianbo Liang
OBJECTIVE: The study was performed to investigate the association of interleukin 17 (IL 17) or angiotensin II (Ang II) with refractory hypertension risk in hemodialysis patients. METHODS: Ninety hemodialysis patients were enrolled into this study, and those with hypertension were divided into two groups. The Easy-to-Control Hypertension group (ECHG) had fifty patients, while the refractory hypertension group (RHG) had forty patients. Twenty healthy individuals were recruited as the control group...
September 2016: African Health Sciences
https://www.readbyqxmd.com/read/27916702/chronic-kidney-disease-accelerates-cognitive-impairment-in-a-mouse-model-of-alzheimer-s-disease-through-angiotensin-ii
#10
Takashi Nakagawa, Yu Hasegawa, Ken Uekawa, Shokei Kim-Mitsuyama
Epidemiological studies suggest that chronic kidney disease (CKD) is a significant risk factor in the development of cognitive decline. However, the exact role of CKD in cognitive impairment or dementia is unclear. This work was performed to examine the potential impact of CKD on cognitive impairment in Alzheimer's disease (AD), focusing on angiotensin II. (1) CKD was induced in 5XFAD mice, an AD model mouse, and wild-type mice by feeding adenine-containing diet and the effect on cognitive function was compared between both strains...
December 1, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27916218/fenofibrate-attenuates-malignant-hypertension-by-suppression-of-the-renin-angiotensin-system-a-study-in-cyp1a1-ren-2-transgenic-rats
#11
Šárka Jíchová, Šárka Doleželová, Libor Kopkan, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Luděk Červenka
BACKGROUND: Malignant hypertension is a life-threatening condition, and its pathophysiology is still poorly understood. The present study was designed to evaluate the role of interaction of the renin-angiotensin system with 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway, in the pathophysiology of angiotensin II (ANG II)-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. METHODS: Malignant hypertension was induced by 12 days׳ dietary administration of 0...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27915452/chronic-enalapril-treatment-increases-transient-outward-potassium-current-in-cardiomyocytes-isolated-from-right-ventricle-of-spontaneously-hypertensive-rats
#12
Luiz Fernando Rodrigues Junior, Ana Carolina de Azevedo Carvalho, Enildo Broetto Pimentel, José Geraldo Mill, José Hamilton Matheus Nascimento
It has been well established that chronic pressure overload resulting from hypertension leads to ventricular hypertrophy and electrophysiological remodeling. The transient outward potassium current (I to) reduction described in hypertensive animals delays ventricular repolarization, leading to complex ventricular arrhythmias and sudden death. Antihypertensive drugs, as angiotensin-converting enzyme inhibitors (ACEi), can restore I to and reduce the incidence of arrhythmic events. The purpose of this study was to evaluate the differential effects of long-term treatment with ACEi or direct-acting smooth muscle relaxant on the I to of left and right ventricle myocytes of spontaneously hypertensive rats (SHR)...
December 3, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27915093/discoidin-domain-receptor-1-kinase-activity-is-required-for-regulating-collagen-iv-synthesis
#13
Corina M Borza, Yan Su, Truc-Linh Tran, Ling Yu, Nick Steyns, Kayla J Temple, Marcin J Skwark, Jens Meiler, Craig W Lindsley, Brennan R Hicks, Birgit Leitinger, Roy Zent, Ambra Pozzi
Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds to and is activated by collagens. DDR1 expression increases following kidney injury and accumulating evidence suggests that it contributes to the progression of injury. To this end, deletion of DDR1 is beneficial in ameliorating kidney injury induced by angiotensin infusion, unilateral ureteral obstruction, or nephrotoxic nephritis. Most of the beneficial effects observed in the DDR1-null mice are attributed to reduced inflammatory cell infiltration to the site of injury, suggesting that DDR1 plays a pro-inflammatory effect...
November 30, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27914612/dexamethasone-induced-diuresis-is-associated-with-inhibition-of-the-renin-angiotensin-aldosterone-system-in-rats
#14
Chao Liu, Ning Ge, Jian-Long Zhai, Jian-Xin Zhang
In heart failure (HF) patients, diuretics remain the cornerstone of therapy to relieve fluid retention. However, the resulting volume loss activates the renin-angiotensin-aldosterone system (RAAS), which blunts the decline in volume depletion and blood pressure. RAAS activation, in turn, compromises the diuretic decongesting effect. Although corticosteroids can induce potent diuresis in HF patients, the effects of corticosteroids on RAAS activation remain unclear. Therefore, we assessed the effects of dexamethasone (Dex) on urine output and plasma angiotensin II and aldosterone levels in rats following water deprivation-induced dehydration, following induction of chronic HF (CHF), and following induction of CHF and volume expansion therapy...
December 2016: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/27913661/effects-of-exendin-4-on-the-intrarenal-renin-angiotensin-system-and-interstitial-fibrosis-in-unilateral-ureteral-obstruction-mice-exendin-4-and-unilateral-ureteral-obstruction
#15
Ying Le, Zongji Zheng, Junyu Xue, Mengling Cheng, Meiping Guan, Yaoming Xue
OBJECTIVE: The objective of this article is to investigate the renoprotecive effects of exendin-4 in a mouse model of unilateral ureteral obstruction (UUO) and explore the putative mechanisms. METHODS: Male Balbc mice underwent sham operation or UUO surgery, and then received intraperitoneal injection of vehicle or exendin-4, respectively. After 14 days, mice were sacrificed and the left kidneys were collected and analyzed by histology, immunohistochemistry, Western blot, quantitative real-time reverse transcription polymerase chain reaction, radioimmunoassay and enzyme-linked immunosorbent assay...
October 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27913306/effect-of-bradykinin-receptor-antagonism-on-ace-inhibitor-associated-angioedema
#16
Brittany T Straka, Claudia E Ramirez, James B Byrd, Elizabeth Stone, Alencia Woodard-Grice, Hui Nian, Chang Yu, Aleena Banerji, Nancy J Brown
BACKGROUND: The B2 receptor antagonist icatibant is approved for treatment of attacks of hereditary angioedema. Icatibant has been reported to decrease time-to-resolution of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema in one study of European patients. METHODS: Patients with ACE inhibitor-associated angioedema (defined as swelling of lips, tongue, pharynx or face during ACE inhibitor use and no swelling in the absence of ACE inhibitor use) were enrolled at Vanderbilt University Medical Center from October 2007 through September 2015 and at Massachusetts General Hospital in 2012...
November 29, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27912890/persistence-of-123-i-mibg-prognostic-capability-in-relation-to-medical-therapy-in-heart-failure-from-the-admire-hf-trial
#17
Ileana L Piña, Peter Carson, JoAnn Lindenfeld, W Tad Archambault, Arnold F Jacobson
(123)I-mIBG imaging has been evaluated to assess sympathetic function and prognosis in heart failure (HF). However, the effect of combined HF medical therapies on (123)I-mIBG uptake and its prognostic significance has not been previously examined. This analysis examined the relation between the intensity of guideline-directed HF medical therapy and global (123)I-mIBG cardiac uptake in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) database. A second objective was to investigate whether this guideline-based therapy, measured by total medication doses, had the expected effect on outcome, that is, that patients with higher (123)I-mIBG cardiac uptake and more intensive medical therapy had the fewest outcome events...
October 31, 2016: American Journal of Cardiology
https://www.readbyqxmd.com/read/27912208/smad-nuclear-interacting-protein-1-acts-as-a-protective-regulator-of-pressure-overload-induced-pathological-cardiac-hypertrophy
#18
Yu-Yan Lu, Da-Chun Xu, Yi-Fan Zhao, Guo-Fu Zhu, Meng-Yun Zhu, Wei-Jing Liu, Xue-Jing Yu, Wei Chen, Zheng Liu, Ya-Wei Xu
BACKGROUND: Smad nuclear interacting protein 1 (SNIP1) plays a critical role in cell proliferation, transformation of embryonic fibroblasts, and immune regulation. However, the role of SNIP1 in cardiac hypertrophy remains unclear. METHODS AND RESULTS: Here we examined the role of SNIP1 in pressure overload-induced cardiac hypertrophy and its mechanisms. Our results demonstrated that SNIP1 expression was downregulated in human dilated cardiomyopathic hearts, aortic banding-induced mice hearts, and angiotensin II-treated cardiomyocytes...
October 26, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27911784/%C3%AE-arrestin-mediates-the-frank-starling-mechanism-of-cardiac-contractility
#19
Dennis M Abraham, Robert T Davis, Chad M Warren, Lan Mao, Beata M Wolska, R John Solaro, Howard A Rockman
The Frank-Starling law of the heart is a physiological phenomenon that describes an intrinsic property of heart muscle in which increased cardiac filling leads to enhanced cardiac contractility. Identified more than a century ago, the Frank-Starling relationship is currently known to involve length-dependent enhancement of cardiac myofilament Ca(2+) sensitivity. However, the upstream molecular events that link cellular stretch to the length-dependent myofilament Ca(2+) sensitivity are poorly understood. Because the angiotensin II type 1 receptor (AT1R) and the multifunctional transducer protein β-arrestin have been shown to mediate mechanosensitive cellular signaling, we tested the hypothesis that these two proteins are involved in the Frank-Starling mechanism of the heart...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27910955/pgc-1%C3%AE-dictates-endothelial-function-through-regulation-of-enos-expression
#20
Siobhan M Craige, Swenja Kröller-Schön, Chunying Li, Shashi Kant, Shenghe Cai, Kai Chen, Mayur M Contractor, Yongmei Pei, Eberhard Schulz, John F Keaney
Endothelial dysfunction is a characteristic of many vascular related diseases such as hypertension. Peroxisome proliferator activated receptor gamma, coactivator 1α (PGC-1α) is a unique stress sensor that largely acts to promote adaptive responses. Therefore, we sought to define the role of endothelial PGC-1α in vascular function using mice with endothelial specific loss of function (PGC-1α EC KO) and endothelial specific gain of function (PGC-1α EC TG). Here we report that endothelial PGC-1α is suppressed in angiotensin-II (ATII)-induced hypertension...
December 2, 2016: Scientific Reports
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