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beta adrenergic signaling cardiac fibrosis

Alicia Jurado Acosta, Jaana Rysä, Zoltan Szabo, Anne-Mari Moilanen, Hiba Komati, Mona Nemer, Heikki Ruskoaho
The phenylephrine-induced complex-1 (PEX1) transcription factor, also known as zinc-finger protein 260 (Zfp260), is an effector of endothelin-1 and α1-adrenergic signaling in cardiac hypertrophy. However, the role of PEX1 in transcriptional regulation of myocardial remodeling remains largely unknown. In the present study, we used PEX1 gain- and loss-of-function to examine the effects of PEX1 on left ventricular remodeling. Adenoviral constructs expressing PEX1, antisense PEX1, or LacZ were delivered by local injection into the anterior wall of the left ventricle in Sprague-Dawley rats...
February 2017: Cell and Tissue Research
Longyan Yang, Junfang Zheng, Ying Xiong, Ran Meng, Qian Ma, Hua Liu, Hui Shen, Shuai Zheng, Songlin Wang, Junqi He
The beta-2 adrenergic receptor (β2AR), a member of GPCR, can activate multiple signaling pathways and is an important treatment target for cardiac failure. However, the molecular mechanism about β2AR signaling regulation is not fully understood. In this study, we found that cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) overexpression reduced β2AR-mediated extracellular signal-regulated kinase-1/2 (ERK1/2) activation. Further study identified CAL as a novel binding partner of β2AR...
July 2015: Amino Acids
Natsumi Matsuura, Kai Nagasawa, Yuji Minagawa, Shogo Ito, Yusuke Sano, Yuichiro Yamada, Takuya Hattori, Shogo Watanabe, Toyoaki Murohara, Kohzo Nagata
Restraint stress stimulates sympathetic nerve activity and can affect adiposity and metabolism. However, the effects of restraint stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We investigated the effects of chronic restraint stress and β-adrenergic receptor (β-AR) blockade on cardiac and adipose tissue pathology and metabolic disorders in a rat model of MetS. DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats...
May 15, 2015: American Journal of Physiology. Heart and Circulatory Physiology
Laurel A Grisanti, Ashley A Repas, Jennifer A Talarico, Jessica I Gold, Rhonda L Carter, Walter J Koch, Douglas G Tilley
Chronic stimulation of β-adrenergic receptors (βAR) can promote survival signaling via transactivation of epidermal growth factor receptor (EGFR) but ultimately alters cardiac structure and contractility over time, in part via enhanced cytokine signaling. We hypothesized that chronic catecholamine signaling will have a temporal impact on cardiac transcript expression in vivo, in particular cytokines, and that EGFR transactivation plays a role in this process. C57BL/6 mice underwent infusion with vehicle or isoproterenol (Iso)±gefitinib (Gef) for 1 or 2 wk...
February 15, 2015: American Journal of Physiology. Heart and Circulatory Physiology
Jiangbo Yu, Shusen Yang, Xu Wang, Runtao Gan
Matrine, an alkaloid isolated from the traditional Chinese medicine Sophora flavescens AIT has exhibited a number of therapeutic effects on cardiovascular and liver diseases. The purpose of the present study was to investigate whether matrine has a protective effect on heart failure in rats. Coronary artery ligation was used to induce a heart failure (CHF) model in rats. Four weeks following the procedure, the rats were treated with different doses of matrine for one month. Histopathological examination demonstrated that matrine treatment alleviated myocardial hypertrophy and cardiac fibrosis in failing hearts...
December 2014: Molecular Medicine Reports
Lin Yan, Stephen F Vatner, Dorothy E Vatner
β-Adrenergic receptor (β-AR) blockade is widely used to treat heart failure, since the adverse effects of chronic β-AR stimulation are central to the pathogenesis of this disease state. Transgenic (Tg) mice, where β-AR signaling is chronically enhanced by overexpression of cardiac β₂-ARs, is a surrogate for this mechanism, since these mice develop cardiomyopathy as reflected by reduced left ventricular (LV) function, increased fibrosis, apoptosis, and myocyte hypertrophy. We hypothesized that disruption of type 5 adenylyl cyclase (AC5), which is in the β-AR signaling pathway in the heart, but exerts only a minor β-AR blocking effect, could prevent the cardiomyopathy in β₂-AR Tg mice without the negative effects of full β-AR blockade...
November 15, 2014: American Journal of Physiology. Heart and Circulatory Physiology
Jinju Li, Jennifer L Philip, Xianyao Xu, Tiju Theccanat, M Abdur Razzaque, Shahab A Akhter
Cardiac fibroblasts (CFs) produce and degrade the myocardial extracellular matrix and are critical in maladaptive ventricular remodeling that can result in heart failure (HF). β-Arrestins are important signaling molecules involved in β-adrenergic receptor (β-AR) desensitization and can also mediate signaling in a G protein-independent fashion. We hypothesize that β-arrestins play an important role in the regulation of adult human CF biology with regard to myofibroblast transformation, increased collagen synthesis, and myocardial fibrosis which are important in the development of HF...
November 2014: Journal of Molecular and Cellular Cardiology
Xiaolin Niu, Lianyou Zhao, Xue Li, Yusheng Xue, Bin Wang, Zongqiang Lv, Jianghong Chen, Dongdong Sun, Qiangsun Zheng
β3-adrenergic receptor (AR) and the downstream signaling, nitric oxide synthase (NOS) isoforms, have been emerged as novel modulators of heart function and even potential therapeutic targets for cardiovascular diseases. However, it is not known whether β3-AR plays cardioprotective effects against myocardial infarction (MI) injury. Therefore, the present study was designed to determine the effects of β3-AR on MI injury and to elucidate the underlying mechanism. MI model was constructed by left anterior descending (LAD) artery ligation...
2014: PloS One
Haiyan Lu, Aiju Tian, Jimin Wu, Chengzhi Yang, Rui Xing, Pu Jia, Lingjian Yang, Youyi Zhang, Xiaohui Zheng, Zijian Li
Danshensu, the effective ingredient of the plant Salvia miltiorrhiza (Danshen), has been widely used for treatment of cardiovascular diseases. Cardiac fibrosis is an important process in pathological cardiac remodeling and leads to heart failure. We investigated the effect of Danshensu on β-adrenergic receptor (β-AR)-mediated cardiac fibrosis and the involved signaling transduction. Danshensu inhibited cardiofibroblast proliferation and collagen I synthesis induced by isoproterenol (ISO), a selective β-AR agonist...
2014: Biological & Pharmaceutical Bulletin
Zheng Zhang, Liping Ding, Zhitao Jin, Guojie Gao, Huijun Li, Lijuan Zhang, Lina Zhang, Xin Lu, Lihua Hu, Bingwei Lu, Xiongjun Yu, Taohong Hu
Nebivolol, third-generation β-blocker, may activate β3-adrenergic receptor (AR), which has been emerged as a novel and potential therapeutic targets for cardiovascular diseases. However, it is not known whether nebivolol administration plays a cardioprotective effect against myocardial infarction (MI) injury. Therefore, the present study was designed to clarify the effects of nebivolol on MI injury and to elucidate the underlying mechanism. MI model was constructed by left anterior descending (LAD) artery ligation...
2014: PloS One
Liang Yang, Zhe Jia, Lei Yang, Mengmeng Zhu, Jincai Zhang, Jie Liu, Ping Wu, Wencong Tian, Jing Li, Zhi Qi, Xiangdong Tang
Extensive data have shown that exercise training can provide cardio-protection against pathological cardiac hypertrophy. However, how long the heart can retain cardio-protective phenotype after the cessation of exercise is currently unknown. In this study, we investigated the time course of the loss of cardio-protection after cessation of exercise and the signaling molecules that are responsible for the possible sustained protection. Mice were made to run on a treadmill six times a week for 4 weeks and then rested for a period of 0, 1, 2 and 4 weeks followed by isoproterenol injection for 8 days...
2014: PloS One
Alessandra Castaldi, Tania Zaglia, Vittoria Di Mauro, Pierluigi Carullo, Giacomo Viggiani, Giulia Borile, Barbara Di Stefano, Gabriele Giacomo Schiattarella, Maria Giovanna Gualazzi, Leonardo Elia, Giuliano Giuseppe Stirparo, Maria Luisa Colorito, Gianluigi Pironti, Paolo Kunderfranco, Giovanni Esposito, Marie-Louise Bang, Marco Mongillo, Gianluigi Condorelli, Daniele Catalucci
RATIONALE: The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, overactivation of the sympathetic nervous system induces the release of catecholamines, which activate β-adrenergic receptors in cardiomyocytes and lead to increased heart rate and cardiac contractility. However, chronic stimulation of β-adrenergic receptors leads to impaired cardiac function, and β-blockers are widely used as therapeutic agents for the treatment of cardiac disease...
July 7, 2014: Circulation Research
Ning Liu, Rui Xing, Chengzhi Yang, Aiju Tian, Zhizhen Lv, Ningning Sun, Xiang Gao, Youyi Zhang, Zijian Li
The activation of β-adrenergic receptors (β-ARs) plays a key role in regulating cardiac function. However, the detailed regulatory mechanisms of β-AR-induced fibrosis are still unclear. We used a proteomics approach to analyze the changes in protein expression patterns in cardiac fibrosis with β-AR stimulation. HIP-55 (also called debrin-like; DBNL) was revealed as a novel regulator in the signaling regulatory network with β-AR activation. Further studies of both HIP-55-overexpressed and -deficient cardiac fibroblasts indicated that HIP-55 negatively regulated β-AR-activated cardiac fibroblast proliferation and the proliferative signaling pathway may be associated with the extracellular signal-regulated protein kinase (ERK) activation...
July 2014: Molecular BioSystems
E R Wang, A A Jarrah, L Benard, J Chen, M Schwarzkopf, L Hadri, S T Tarzami
Altered alpha- and beta-adrenergic receptor signaling is associated with cardiac hypertrophy and failure. Stromal cell-derived factor-1α (SDF-1α) and its cognate receptor CXCR4 have been reported to mediate cardioprotection after injury through the mobilization of stem cells into injured tissue. However, little is known regarding whether SDF-1/CXCR4 induces acute protection following pathological hypertrophy and if so, by what molecular mechanism. We have previously reported that CXCR4 physically interacts with the beta-2 adrenergic receptor and modulates its downstream signaling...
May 2014: Gene Therapy
Guido Tarone, Jean-Luc Balligand, Johann Bauersachs, Angela Clerk, Leon De Windt, Stephane Heymans, Denise Hilfiker-Kleiner, Emilio Hirsch, Guido Iaccarino, Ralph Knöll, Adelino F Leite-Moreira, André P Lourenço, Manuel Mayr, Thomas Thum, Carlo G Tocchetti
The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation...
May 2014: European Journal of Heart Failure
Shoji Iwaya, Masayoshi Oikawa, Yan Chen, Yasuchika Takeishi
Accumulating evidence suggests that there are direct interactions between β-adrenergic and angiotensin II signaling pathways, and β-blockers protect the heart against angiotensin II-induced cardiac remodeling. Phosphodiesterase 3A (PDE3A) regulates β-adrenergic receptor/protein kinase A signaling by metabolizing cAMP. Therefore, we hypothesized that overexpressed PDE3A has cardioprotective effects against angiotensin II-induced cardiac remodeling by regulating angiotensin II signaling. In the present study, we used transgenic mice with cardiac-specific overexpressed PDE3A1...
2014: International Heart Journal
C Vettel, S Lämmle, S Ewens, C Cervirgen, J Emons, A Ongherth, M Dewenter, D Lindner, D Westermann, V O Nikolaev, S Lutz, W H Zimmermann, A El-Armouche
Recent studies suggest that the signal molecules cAMP and cGMP have antifibrotic effects by negatively regulating pathways associated with fibroblast to myofibroblast (MyoCF) conversion. The phosphodiesterase 2 (PDE2) has the unique property to be stimulated by cGMP, which leads to a remarkable increase in cAMP hydrolysis and thus mediates a negative cross-talk between both pathways. PDE2 has been recently investigated in cardiomyocytes; here we specifically addressed its role in fibroblast conversion and cardiac fibrosis...
April 15, 2014: American Journal of Physiology. Heart and Circulatory Physiology
Ge Li-Sha, Chen Yi-He, Zhou Na-Dan, Zhang Teng, Li Yue-Chun
BACKGROUND: The role of β-adrenergic stimulation on viral myocarditis has been investigated in animal models of viral myocarditis. Excess stimulation of β-adrenergic receptors by catecholamines causes phosphorylation/activation of cAMP response element binding protein (CREB) by the cAMP signaling pathway. CREB as an important regulator of gene expression mediates the cardiovascular remodeling process and promotes anti-inflammatory immune responses. However, the CREB expression and phosphorylation have not been studied, and the effects of carvedilol (a nonselective β-adrenoceptor antagonist) on the CREB has not been investigated in the setting of acute viral myocarditis...
November 14, 2013: BMC Cardiovascular Disorders
Catharina Belge, Joanna Hammond, Emilie Dubois-Deruy, Boris Manoury, Julien Hamelet, Christophe Beauloye, Andreas Markl, Anne-Catherine Pouleur, Luc Bertrand, Hrag Esfahani, Karima Jnaoui, Konrad R Götz, Viacheslav O Nikolaev, Annelies Vanderper, Paul Herijgers, Irina Lobysheva, Guido Iaccarino, Denise Hilfiker-Kleiner, Geneviève Tavernier, Dominique Langin, Chantal Dessy, Jean-Luc Balligand
BACKGROUND: β1-2-adrenergic receptors (AR) are key regulators of cardiac contractility and remodeling in response to catecholamines. β3-AR expression is enhanced in diseased human myocardium, but its impact on remodeling is unknown. METHODS AND RESULTS: Mice with cardiac myocyte-specific expression of human β3-AR (β3-TG) and wild-type (WT) littermates were used to compare myocardial remodeling in response to isoproterenol (Iso) or Angiotensin II (Ang II). β3-TG and WT had similar morphometric and hemodynamic parameters at baseline...
January 28, 2014: Circulation
Jochen Springer, Anika Tschirner, Arash Haghikia, Stephan von Haehling, Hind Lal, Aleksandra Grzesiak, Elena Kaschina, Sandra Palus, Mareike Pötsch, Karoline von Websky, Berthold Hocher, Celine Latouche, Frederic Jaisser, Lars Morawietz, Andrew J S Coats, John Beadle, Josep M Argiles, Thomas Thum, Gabor Földes, Wolfram Doehner, Denise Hilfiker-Kleiner, Thomas Force, Stefan D Anker
AIMS: Symptoms of cancer cachexia (CC) include fatigue, shortness of breath, and impaired exercise capacity, which are also hallmark symptoms of heart failure (HF). Herein, we evaluate the effects of drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development of cardiac wasting, HF, and death in the rat hepatoma CC model (AH-130). METHODS AND RESULTS: Tumour-bearing rats showed a progressive loss of body weight and left-ventricular (LV) mass that was associated with a progressive deterioration in cardiac function...
April 2014: European Heart Journal
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