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Reverse remodeling

Michel Komajda
Ivabradine is a blocker of the funny current channels in the sinoatrial node cells. This results in pure heart rate reduction when elevated without direct effect on contractility or on the vessels. It was tested in a large outcome clinical trial in stable chronic heart failure (CHF) with low ejection fraction, in sinus rhythm, on a contemporary background therapy including betablockers (SHIFT: Systolic Heart Failure Treatment with the If inhibitor Trial).The primary composite endpoint (cardiovascular mortality or heart failure hospitalization) was reduced by 18% whereas the first occurrence of heart failure hospitalizations was reduced by 26%...
October 18, 2016: Handbook of Experimental Pharmacology
Naoshi Nishida, Masatoshi Kudo
Accumulation of genetic and epigenetic alterations is a hallmark of cancer genomes, including those in hepatocellular carcinoma (HCC). Particularly, in human HCC, epigenetic changes are more frequently observed than genetic changes in a variety of cancer-related genes, suggesting a potential role for epigenetic alterations during hepatocarcinogenesis. Several environmental factors, such as inflammation, obesity, and steatosis, are reported to affect the epigenetic status in hepatocytes, which could play a role in HCC development...
2016: Digestive Diseases
Masaaki Ikeda, Yoshitaka Yoshimura, Takashi Kikuiri, Mino Matsuno, Tomokazu Hasegawa, Kumu Fukushima, Takako Hayakawa, Hajime Minamikawa, Kuniaki Suzuki, Junichiro Iida
Bone remodeling is an important factor in orthodontic tooth movement. During orthodontic treatment, osteoclasts are subjected to various mechanical stimuli, and this promotes or inhibits osteoclast differentiation and fusion. It has been previously reported that the release from tensile force induces osteoclast differentiation. However, little is known about how release from compressive force affects osteoclasts. The present study investigated the effects of release from compressive force on osteoclasts. The number of tartrate‑resistant acid phosphatase (TRAP)‑positive multinucleated osteoclasts derived from RAW264...
October 5, 2016: Molecular Medicine Reports
Kuo Zhang, Jingyu Yang, Fang Wang, Xing Pan, Jian Liu, Lijuan Wang, Guanyue Su, Jie Ma, Yinxu Dong, Zhili Xiong, Chufu Wu
ETHNOPHARMACOLOGICAL RELEVANCE: Hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis is often observed in the pathophysiology of depression. Antidepressant therapy can restore hippocampal neurogenesis to rescue the HPA axis regulation defects. Xiaochaihutang (XCHT), a famous Chinese herbal formula, has been used clinically in depressive disorders in China. Our previous studies have demonstrated XCHT improved depressive-like behaviors in chronic unpredictable mild stress rat, but the underlying mechanisms of XCHT on hippocampal neurogenesis and the HPA axis were still unclear...
October 13, 2016: Journal of Ethnopharmacology
Peng Li, Pei-Pei Huang, Yun Yang, Chi Liu, Yan Lu, Fang Wang, Wei Sun, Xiang-Qing Kong
Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then, rats underwent RSD or sham 4 weeks later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD)...
October 14, 2016: Journal of Applied Physiology
Gen Suzuki, Rebeccah F Young, Merced M Leiker, Takayuki Suzuki
A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 10(6) microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 10(6), n = 5) or saline (untreated, n = 6)...
2016: Stem Cells International
Shweta R Motiwala, Hanna K Gaggin
Left ventricular remodeling appears to be a critical link between cardiac injury and the development and progression of heart failure with reduced ejection fraction (HFrEF). Several drug and device therapies that modify and reverse the remodeling process in patients with HFrEF are closely associated with improvement in clinical outcomes. Reverse remodeling, including partial or complete recovery of systolic function and structure, is possible but its determinants are incompletely understood. Methods to predict reverse remodeling in response to therapy are not well defined...
October 10, 2016: Current Heart Failure Reports
Qianwen Gong, Miroslaw Janowski, Mingkun Xie, Guoyuan Yang, Longqian Liu
BACKGROUND: Genome-wide association studies of patients have linked the Rasgrf1 gene with myopia. The aim of this study was to investigate the messenger RNA (mRNA) expression of Rasgrf1 in the eyes of guinea pigs with induced myopia. METHODS: The myopia was induced by form deprivation in 24 guinea pigs, while additional 12 animals served as a control. Biometric measurements were used to monitor myopic progression. The animals were sacrificed at two, three and four weeks after beginning of the monocular form deprivation, followed by dissection of the retina, and the sclera, as well as mRNA isolation from both layers...
October 9, 2016: Clinical & Experimental Optometry: Journal of the Australian Optometrical Association
Pieter Martens, Frederik H Verbrugge, Petra Nijst, Matthias Dupont, Wilfried Mullens
BACKGROUND: Cardiac resynchronization therapy (CRT) improves morbidity and mortality in heart failure with reduced ejection fraction (HFrEF) and electrical dyssynchrony. CRT patients in clinical practice are older compared to clinical trials. OBJECTIVE: To investigate clinical response, reverse remodeling, outcome and mode of death in octogenarians receiving CRT. METHODS: Baseline characteristics, change in New York Heart Association (NYHA) functional class, reverse ventricular remodeling, heart failure readmissions, all-cause mortality and mode of death were evaluated in CRT patients with comparison between octogenarians and non-octogenarians...
October 4, 2016: Journal of Cardiac Failure
Johannes Schöneberg, Il-Hyung Lee, Janet H Iwasa, James H Hurley
The narrow membrane necks formed during viral, exosomal and intra-endosomal budding from membranes, as well as during cytokinesis and related processes, have interiors that are contiguous with the cytosol. Severing these necks involves action from the opposite face of the membrane as occurs during the well-characterized formation of coated vesicles. This 'reverse' (or 'inverse')-topology membrane scission is carried out by the endosomal sorting complex required for transport (ESCRT) proteins, which form filaments, flat spirals, tubes and conical funnels that are thought to direct membrane remodelling and scission...
October 5, 2016: Nature Reviews. Molecular Cell Biology
Renn-Chia Lin, Ko-Huang Lue, Ko-Hsiu Lu
To evaluate whether arthroscopic lateral retinacular release and the modified Elmslie-Trillat operation improve osteoarthritis (OA) progression and clinical outcomes in patients with severe isolated lateral patello-femoral OA. Nine women (11 knees) and one man (one knee) with isolated late-stage lateral patello-femoral OA underwent surgery. The severity of patello-femoral OA was recorded using the Merchant method, while the level of pain and anterior knee function were scored using the visual analogue scale (VAS) and Kujala knee scores, respectively...
October 3, 2016: Journal of Knee Surgery
Xiuqing Tian, Qing Wang, Rui Guo, Lingling Xu, Qin M Chen, Yinglong Hou
BACKGROUND: Paroxetine is a selective serotonin reuptake inhibitor utilized in the treatment of depression and anxiety disorders. Recent studies have identified paroxetine as a G protein-coupled receptor kinase-2 (GRK2) inhibitor capable of reversing cardiac dysfunction and remodeling in experimental models of acute myocardial infarction (AMI). We determine the clinical importance of paroxetine on cardiac functions in patients having AMI with depression (AMID) in comparison with fluoxetine, an unrelated selective serotonin reuptake inhibitor that does not inhibit GRK2...
2016: Neuropsychiatric Disease and Treatment
Mathew J Wong, Crystal Kantores, Julijana Ivanovska, Amish Jain, Robert P Jankov
Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but at the cost of severe adverse effects, including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoid intermediates that may limit activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that statin treatment would safely limit pulmonary vascular RhoA activity and prevent and reverse experimental chronic neonatal PHT via downstream inhibitory effects on pathological ROCK activity...
September 30, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Antoine Heni Chaanine, Erik Kohlbrenner, Scott I Gamb, Adam J Guenzel, Katherine A Klaus, Ahmed U Fayyaz, K Sreekumaran Nair, Roger J Hajjar, Margaret M Redfield
The Forkhead box O3a (FOXO3a) transcription factor has been shown to regulate glucose metabolism, muscle atrophy and cell death in post-mitotic cells. Its role in regulating mitochondrial and myocardial function is not well studied. Based on previous work, we hypothesized that FOXO3a, through BNIP3, modulates mitochondrial morphology and function in HF. We modulated the FOXO3a-BNIP3 pathway in normal and phenylephrine (PE) stressed adult cardiac myocytes (ACM) in vitro and developed a cardiotropic adeno-associated virus serotype 9 encoding dominant-negative FOXO3a (AAV9...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Anna M May, David R Van Wagoner, Reena Mehra
A surge of data has reproducibly identified strong associations of obstructive sleep apnea (OSA) with cardiac arrhythmias. As an extension of epidemiologic and clinic-based findings, experimental investigations have made strides in advancing our understanding of the putative OSA and cardiac arrhythmogenesis mechanistic underpinnings. While most studies have focused on the links between OSA and atrial fibrillation (AF), relationships with ventricular arrhythmias have also been characterized. Key findings implicate OSA-related autonomic nervous system fluctuations typified by enhanced parasympathetic activation during and sympathetic surges subsequent to respiratory events which contribute to augmented arrhythmic propensity...
September 29, 2016: Chest
Qihai Xie, Tong Wei, Chenglin Huang, Penghao Liu, Mengwei Sun, Weili Shen, Pingjin Gao
NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d)...
September 30, 2016: Scientific Reports
Van-Khue Ton, Gordana Vunjak-Novakovic, Veli K Topkara
Left ventricular assist device (LVAD) therapy has revolutionized the treatment of patients with advanced heart failure. Although originally intended for bridge-to-transplantation and destination therapy indications, a small subset of patients supported with LVADs exhibit complete myocardial recovery leading to device explanation. However, genetic and molecular determinants of partial and/or complete myocardial recovery remain largely unknown. Areas covered: We summarize current knowledge on alterations in heart failure transcriptome in response to LVAD support, as well as discuss common gene signatures potentially responsible for the reverse remodeling phenotype in the failing human heart...
October 14, 2016: Expert Review of Medical Devices
Keytam S Awad, James D West, Vinicio de Jesus Perez, Margaret MacLean
The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis...
September 2016: Pulmonary Circulation
Michael M Kreusser, Lorenz H Lehmann, Nora Wolf, Stanislav Keranov, Andreas Jungmann, Hermann-Josef Gröne, Oliver J Müller, Hugo A Katus, Johannes Backs
CaM kinase II (CaMKII) has been suggested to drive pathological cardiac remodeling and heart failure. However, the evidence provided so far is based on inhibitory strategies using chemical compounds and peptides that also exert off-target effects and followed exclusively preventive strategies. Therefore, the aim of this study was to investigate whether specific CaMKII inhibition after the onset of cardiac stress delays or reverses maladaptive cardiac remodeling and dysfunction. Combined genetic deletion of the two redundant CaMKII genes δ and γ was induced after the onset of overt heart failure as the result of pathological pressure overload induced by transverse aortic constriction (TAC)...
November 2016: Basic Research in Cardiology
Hiroki Daijo, Yuma Hoshino, Shinichi Kai, Kengo Suzuki, Kenichiro Nishi, Yoshiyuki Matsuo, Hiroshi Harada, Kiichi Hirota
Cigarette smoke (CS) is a major contributor to the development of a large number of fatal and debilitating disorders. However, the precise molecular mechanisms underlying the effects of CS in lung disease are largely unknown. To elucidate these pathophysiological processes, we examined the in vitro and in vivo effects of CS extract (CSE) and CS on the transcription factor, hypoxia-inducible factor 1 (HIF-1). CSE induced concentration- and time-dependent accumulation of HIF-1α protein in human lung epithelial-like cells under non-hypoxic conditions...
September 29, 2016: Scientific Reports
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