Angiotensin II Receptor Antagonist Blocks the Expression of Connexin43 Induced by Cyclical Mechanical Stretch in Cultured Neonatal Rat Cardiac Myocytes

Shyu, Kou‐Gi; Chen, Chia-Chi; Wang, Baowei; Kuan, Peiliang

doi:10.1006/jmcc.2000.1333

Cited by 84 publications

(68 citation statements)

References 24 publications

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“…Cardiomyocytes were obtained from 2-to 3-day-old Wistar rats as described previously (Shyu et al 2001). Cultured myocytes were O95% pure as revealed by observation of contractile characteristics with a light microscope and were stained with anti-desmin antibody (Dako Cytomation, Glostrup, Denmark).…”

Section: Primary Culture Of Left Ventricular Cardiomyocytesmentioning

confidence: 99%

Angiotensin II and the JNK pathway mediate urotensin II expression in response to hypoxia in rat cardiomyocytes

Chiu¹,

Wang²,

Shyu³

2014

Journal of Endocrinology

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Cardiomyocyte hypoxia causes cardiac hypertrophy through cardiac-restricted gene expression. Urotensin II (UII) cooperates with activating protein 1 (AP1) to regulate cardiomyocyte growth in response to myocardial injuries. Angiotensin II (AngII) stimulates UII expression, reactive oxygen species (ROS) production, and cardiac hypertrophy. This study aimed to evaluate the expression of UII, ROS, and AngII as well as their genetic transcription after hypoxia treatment in neonatal cardiomyocytes. Cultured neonatal rat cardiomyocytes were subjected to hypoxia for different time periods. UII (Uts2) protein levels increased after 2.5% hypoxia for 4 h with earlier expression of AngII and ROS. Both hypoxia and exogenously added AngII or Dp44mT under normoxia stimulated UII expression, whereas AngII receptor blockers, JNK inhibitors (SP600125), JNK siRNA, or N-acetyl-L-cysteine (NAC) suppressed UII expression. The gel shift assay indicated that hypoxia induced an increase in DNA-protein binding between UII and AP1. The luciferase assay confirmed an increase in transcription activity of AP1 to the UII promoter under hypoxia. After hypoxia, an increase in 3 H-proline incorporation in the cardiomyocytes and expression of myosin heavy chain protein, indicative of cardiomyocyte hypertrophy, were observed. In addition, hypoxia increased collagen I expression, which was inhibited by SP600125, NAC, and UII siRNA. In summary, hypoxia in cardiomyocytes increases UII and collagen I expression through the induction of AngII, ROS, and the JNK pathway causing cardiomyocyte hypertrophy and fibrosis.

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Section: Primary Culture Of Left Ventricular Cardiomyocytesmentioning

confidence: 99%

Angiotensin II and the JNK pathway mediate urotensin II expression in response to hypoxia in rat cardiomyocytes

Chiu¹,

Wang²,

Shyu³

2014

Journal of Endocrinology

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“…Researches on drug development reveal that AT 1 antagonist losartan can inhibit the highly elevated expression of Cx43 in the ventricular myocytes of neonatal rats (Zhao et al, 2008). Study also demonstrated that AT 1 antagonist can inhibit the upregulation of Cx43 in rat ventricular myocytes subjected to periodic mechanical stretching (Shyu et al, 2001), suggesting that renin angiotensin system (RAS) played an important role in the remodeling of GJ in ventricular myocytes under pathological conditions (Sun, 2010). Although Cx43 has been studied extensively, its expression and function are largely unknown.…”

Section: Introductionmentioning

confidence: 90%

Effects of Losartan and Ramipril on the connexin expression in a rabbit balloon injury model

Li¹,

Li²,

Duan³

et al. 2011

Afr. J. Pharm. Pharmacol.

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Intercellular gap junction (GJ) plays a pivotal role in the proliferation and transformation of vascular smooth muscle cells (VSMCs). This study was designed to test the hypothesis that expressions of the component proteins of gap junctions, connexins40 and 43 (Cx40 and Cx43), are up-regulated in arteries subjected to balloon injury and that this up-regulation can be suppressed by statin therapy. Transmission electron microscopy (TEM) revealed that there were abundant GJ between neointimal SMCs but fewer and smaller GJ after losartan and ramipril treatment. Reverse transcription-polymerase chain reaction and Western blot analysis showed the messenger ribonucleic acid (mRNA) and protein expressions of Cx40 and Cx43 were elevated after injury, and these elevations were suppressed by losartan and ramipril. Immunostaining showed the Cx40 and Cx43 expressions were consistently enhanced in the neointimal area after injury, which was decreased by losartan and ramipril treatment. Balloon injury causes up-regulation of Cx40 and Cx43 in neointimal SMCs. angiotensin-converting enzyme inhibitors (ACEIs) and AT 1 antagonist losartan can reduce the proliferation of SMCs, suggesting the rennin-angiotensin system (RAS) system plays an important role in the remodeling of GJ in the VSMCs under pathological conditions.

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“…Several groups have shown that cyclic stretch upregulates the expression levels of Cx43 in cultured monolayers of neonatal rat ventricular myocytes (NRVMs) grown on silicone membranes (Wang et al, 2000;Zhuang et al, 2000;Shyu et al, 2001;Pimental et al, 2002;Shanker et al, 2005;Yamada et al, 2005). The stretch-induced upregulation of Cx43 has been related to activation of the Na-H exchanger (Wang et al, 2000), increased secretion of angiotensin II that acts on AT1 receptors (Shyu et al, 2001), secretion of vascular endothelial growth factor (VEGF) acting downstream of TGFβ and FAK in an autocrine fashion (Pimental et al, 2002;Yamada et al, 2005), and type of extracellular matrix protein on which the cells are grown (Shanker et al, 2005).…”

Section: Mef In Nrvm Monolayersmentioning

confidence: 99%

“…The stretch-induced upregulation of Cx43 has been related to activation of the Na-H exchanger (Wang et al, 2000), increased secretion of angiotensin II that acts on AT1 receptors (Shyu et al, 2001), secretion of vascular endothelial growth factor (VEGF) acting downstream of TGFβ and FAK in an autocrine fashion (Pimental et al, 2002;Yamada et al, 2005), and type of extracellular matrix protein on which the cells are grown (Shanker et al, 2005). Uniaxial cyclic stretch induces cell alignment of NRVMs (Terracio et al, 1988;Vandenburgh et al, 1995;Matsuda et al, 2005) and localization of Cx43 at the longitudinal cell termini that is regulated by the Rac1 pathway downstream of N-cadherin (Matsuda et al, 2006).…”

Section: Mef In Nrvm Monolayersmentioning

confidence: 99%

“…In other studies, cyclic stretch of NRVMs grown on silicone membranes coated with RGD or YIGSR peptides were similar in terms of cell adhesion to NRVMs grown on fibronectin or laminin, respectively, but not in terms of normal FAK expression or sarcomere formation (Boeteng et al, 2005). In the experiments described above, stretch was achieved either with vacuum pulses applied to a Flexcell strain unit (Flexcell International Corp., Hillsborough, NC) (Wang et al, 2000;Shyu et al, 2001;Boateng et al, 2005) or with experimental chambers that were custom designed to allow uniaxial stretch (Terracio et al, 1988;Zhuang et al, 2000;Matsuda et al, 2005) or biaxial stretch (Gopalan et al, 2003).…”

Section: Mef In Nrvm Monolayersmentioning

confidence: 99%

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Cell cultures as models of cardiac mechanoelectric feedback

Zhang

Sekar

McCulloch

et al. 2008

Progress in Biophysics and Molecular Biology

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Although stretch-activated currents have been extensively studied in isolated cells and intact hearts in the context of mechanoelectric feedback (MEF) in the heart, quantitative data regarding other mechanical parameters such as pressure, shear, bending, etc, are still lacking at the multicellular level. Cultured cardiac cell monolayers have been used increasingly in the past decade as an in vitro model for the studies of fundamental mechanisms that underlie normal and pathological electrophysiology at the tissue level. Optical mapping makes possible multisite recording and analysis of action potentials and wavefront propagation, suitable for monitoring the electrophysiological activity of the cardiac cell monolayer under a wide variety of controlled mechanical conditions. In this paper, we review methodologies that have been developed or could be used to mechanically perturb cell monolayers, and present some new results on the acute effects of pressure, shear stress and anisotropic strain on cultured neonatal rat ventricular myocyte (NRVM) monolayers.

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Angiotensin II Receptor Antagonist Blocks the Expression of Connexin43 Induced by Cyclical Mechanical Stretch in Cultured Neonatal Rat Cardiac Myocytes

Cited by 84 publications

References 24 publications

Angiotensin II and the JNK pathway mediate urotensin II expression in response to hypoxia in rat cardiomyocytes

Angiotensin II and the JNK pathway mediate urotensin II expression in response to hypoxia in rat cardiomyocytes

Effects of Losartan and Ramipril on the connexin expression in a rabbit balloon injury model

Cell cultures as models of cardiac mechanoelectric feedback

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