AFos inhibits phenylephrine-mediated contractile dysfunction by altering phospholamban phosphorylation

Jeong, Mark Y.; Walker, John S.; Brown, Robert D.; Moore, Russell L.; Vinson, Charles; Colucci, Wilson S.; Long, Carlin S.

doi:10.1152/ajpheart.00937.2009

Cited by 14 publications

(20 citation statements)

References 36 publications

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“…Since ARVM are large cells 26 it is not possible to eliminate dead cells and debris produced during the cell preparation. Only after culturing the cells, unattached cells can be removed in the 2D cell culture.…”

Section: Results and Discussionmentioning

confidence: 99%

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Biomimetic Polymers for Cardiac Tissue Engineering

et al. 2016

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Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies is growing, but sustainability of injected CMs remains a challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided a solution-based delivery vehicle of CMs, which transitioned to a gel-based matrix shortly after reaching body temperature. In this study we tested the suitability of this biopolymer to sustain CM viability. The RTG was biomolecule-functionalized with poly-l-lysine or laminin. Neonatal rat ventricular myocytes (NRVM) and adult rat ventricular myocytes (ARVM) were cultured in plain-RTG and biomolecule-functionalized-RTG both under 3-dimensional (3D) conditions. Traditional 2D biomolecule-coated dishes were used as controls. We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia. Regarding cell contraction, in both RTG and RTG-lysine, beating cells were recorded after 21 days. Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days. These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform.

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Section: Results and Discussionmentioning

confidence: 99%

“…26 All animal studies were performed according to the guidelines of the University of Colorado Denver Animal Care and Use Committee. Briefly, ketamine and xylazine were administered according to the weight of the animal.…”

Section: Materials and Methodsmentioning

confidence: 99%

Biomimetic Polymers for Cardiac Tissue Engineering

et al. 2016

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“…To assess for hypertrophy of ARVMs in the presence of H2O2, total protein concentration was measured as previously described (26). Cells were plated on sixwell plastic culture dishes and pretreated with or without 30 g/ml APN for 18 h. Cells were then treated with 10 M H2O2 for 24 h.…”

Section: Methodsmentioning

confidence: 99%

Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling

Essick¹,

Ouchi²,

Wilson³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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oxygen species (ROS) induce matrix metalloproteinase (MMP) activity that mediates hypertrophy and cardiac remodeling. Adiponectin (APN), an adipokine, modulates cardiac hypertrophy, but it is unknown if APN inhibits ROS-induced cardiomyocyte remodeling. We tested the hypothesis that APN ameliorates ROS-induced cardiomyocyte remodeling and investigated the mechanisms involved. Cultured adult rat ventricular myocytes (ARVM) were pretreated with recombinant APN (30 g/ml, 18 h) followed by exposure to physiologic concentrations of H2O2 (1-200 M). ARVM hypertrophy was measured by [ 3 H]leucine incorporation and atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) gene expression by RT-PCR. MMP activity was assessed by in-gel zymography. ROS was induced with angiotensin (ANG)-II (3.2 mg·kg Ϫ1 ·day Ϫ1 for 14 days) in wild-type (WT) and APN-deficient (APN-KO) mice. Myocardial MMPs, tissue inhibitors of MMPs (TIMPs), p-AMPK, and p-ERK protein expression were determined. APN significantly decreased H2O2-induced cardiomyocyte hypertrophy by decreasing total protein, protein synthesis, ANF, and BNP expression. H2O2-induced MMP-9 and MMP-2 activities were also significantly diminished by APN. APN significantly increased p-AMPK in both nonstimulated and H2O2-treated ARVM. H 2O2-induced p-ERK activity and NF-B activity were both abrogated by APN pretreatment. ANG II significantly decreased myocardial p-AMPK and increased p-ERK expression in vivo in APN-KO vs. WT mice. ANG II infusion enhanced cardiac fibrosis and MMP-2-to-TIMP-2 and MMP-9-to-TIMP-1 ratios in APN-KO vs. WT mice. Thus APN inhibits ROS-induced cardiomyocyte remodeling by activating AMPK and inhibiting ERK signaling and NF-B activity. Its effects on ROS and ultimately on MMP expression define the protective role of APN against ROSinduced cardiac remodeling. reactive oxygen species; adenosine 5=-monophosphate-activated protein kinase; matrix metalloproteinase; cardiomyocyte hypertrophy

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“…First-strand cDNA synthesis was performed using Superscript II reverse transcriptase and random hexamer primers (25). Target gene expression was quantitated by real-time PCR on an iCycler MyiQ with SYBR green supermix (Bio-Rad).…”

Section: Analysis Of Cardiac Gene Expressionmentioning

confidence: 99%

MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension

Brown

Ambler

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Brown RD, Ambler SK, Li M, Sullivan TM, Henry LN, Crossno JT Jr, Long CS, Garrington TP, Stenmark KR. MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 304: H269 -H281, 2013. First published November 2, 2012; doi:10.1152/ajpheart.00158.2012.-Pulmonary hypertension (PH) results in pressure overload of the right ventricle (RV) of the heart, initiating pathological RV remodeling and ultimately leading to right heart failure. Substantial research indicates that signaling through the MAPK superfamily mediates pathological cardiac remodeling. These considerations led us to test the hypothesis that the regulatory protein MAPKKK-2 (MEKK2) contributes to RV hypertrophy in hypoxiainduced PH. Transgenic mice with global knockout of MEKK2 (MEKK2 Ϫ/Ϫ mice) and age-matched wild-type (WT) mice were exposed to chronic hypobaric hypoxia (10% O2, 6 wk) and compared with animals under normoxia. Exposure to chronic hypoxia induced PH in WT and MEKK2 Ϫ/Ϫ mice. In response to PH, WT mice showed RV hypertrophy, demonstrated as increased ratio of RV weight to body weight, increased RV wall thickness at diastole, and increased cardiac myocyte size compared with normoxic control animals. In contrast, each of these measures of RV hypertrophy seen in WT mice after chronic hypoxia was attenuated in MEKK2 Ϫ/Ϫ mice. Furthermore, chronic hypoxia elicited altered programs of hypertrophic and inflammatory gene expression consistent with pathological RV remodeling in WT mice; MEKK2 deletion selectively inhibited inflammatory gene expression compared with WT mice. The actions of MEKK2 were mediated in part through regulation of the abundance and phosphorylation of its effector, ERK5. In conclusion, signaling by MEKK2 contributes to RV hypertrophy and altered myocardial inflammatory gene expression in response to hypoxiainduced PH. Therapies targeting MEKK2 may protect the myocardium from hypertrophy and pathological remodeling in human PH. cardiac remodeling; inflammation; myocytes; hypoxia; pulmonary hypertension; mitogen-activated protein kinase kinase kinase-2; ERK5

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AFos inhibits phenylephrine-mediated contractile dysfunction by altering phospholamban phosphorylation

Cited by 14 publications

References 36 publications

Biomimetic Polymers for Cardiac Tissue Engineering

Biomimetic Polymers for Cardiac Tissue Engineering

Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling

MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension

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