Engineering the niche to differentiate and deploy cardiovascular cells

Increased oxidative stress (OS) is considered a common etiology in the pathogenesis of cardiovascular disease (CVD). Therefore, the precise regulation of reactive oxygen species (ROS) in cardiovascular cells is essential to maintain normal physiological functions. Numerous regulators of cellular homeostasis are reportedly influenced by ROS. Hydrogen peroxide (H2O2), as an endogenous ROS in aerobic cells, is a toxic substance that can induce OS. However, many studies conducted over the past two decades have provided substantial evidence that H2O2 acts as a diffusible intracellular signaling messenger. Antioxidant enzymes, including superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins (Prdxs), maintain the balance of ROS levels against augmentation of ROS production during the pathogenesis of CVD. Especially, Prdxs are regulatory sensors of transduced intracellular signals. The intracellular abundance of Prdxs that specifically react with H2O2 act as regulatory proteins. In this review, we focus on the role of Prdxs in the regulation of ROS-induced pathological changes in the development of CVD.

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Cardiac Repair With Human Pluripotent Stem Cell–Derived Cardiovascular Cells and Arrhythmia Risk

Cardiac Electrophysiology: From Cell to Bedside ◽

10.1016/b978-0-323-44733-1.00058-4 ◽

2018 ◽

pp. 552-558

Author(s):

Timothy J. Kamp

Keyword(s):

Stem Cell ◽

Pluripotent Stem Cell ◽

Cardiac Repair ◽

Human Pluripotent Stem Cell ◽

Cardiovascular Cells

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Abstract 052: Alpha1a-Adrenoceptor Genetic Variant-Triggered Hyperproliferation in Cardiovascular Cells is Mediated by Novel Interacting Protein Spinophilin

Hypertension ◽

10.1161/hyp.64.suppl_1.052 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Ekaterina Babaeva ◽

Irina Gradinaru ◽

Debra A Schwinn ◽

Anush Oganesian

Keyword(s):

Intracellular Signaling ◽

Genetic Variant ◽

Cell Counting ◽

Intracellular Loop ◽

Interacting Protein ◽

Naturally Occurring ◽

Specific Proteins ◽

Cardiovascular Cells ◽

Novel Target ◽

G Protein Coupled

Objectives: Alpha1-Adrenergic Receptors (α1ARs), members of the G protein-coupled receptor (GPCR) superfamily, play a major role in regulating cardiovascular (CV) function. Recently, we discovered that naturally occurring human α1aAR-G247R (247R) genetic variant, identified in the 3rd intracellular loop (3iL) of the receptor in highly hypertensive patient, triggers constitutive hyperproliferation in fibroblasts, cardiomyoblasts and smooth muscle cells (SMC). Specific proteins mediating this signaling remain unknown. Spinophilin (SPL) is a ubiquitously expressed protein controlling GPCR signaling by binding its 3rd intracellular loop (3iL). We hypothesize that SPL mediates α1aAR signaling and examined whether SPL directly interacts with α1aAR-WT (WT) and 247R. Methods: Cells were co-transfected with HA-α1ARs and full length Myc-SPL or its fragments to determine SPL domains responsible for binding to α1ARs. Cell lysates were co-immunoprecipitated with HA-tag antibodies. SPL levels were analyzed by Western blotting. SPL knockdown experiments were performed by transiently transfecting cells with SPL or scrambled siRNA, cell proliferation was determined by cell counting. Results: We demonstrate a distinct interaction of SPL with WT and 247R, WT interaction being the strongest. Different domains of SPL differentially interact with WT or 247R. SPL 1-480aa fragment interacts stronger with WT indicating interaction with 3iL, while SPL 480-817 fragment interacts stronger with 247R. Endogenous SPL levels are increased in 247R cells compared to WT or control cells. Inhibition of SPL expression in SMC with siRNA reduces 247R-triggered hyperproliferation to near normal levels and has no effect in WT cells. Conclusions: We identified SPL as a novel interacting protein involved in mediating intracellular signaling of α1aAR and its genetic variant in CV cells. Different domains of SPL differentially bind to WT or 247R indicating that SPL has a distinct role in regulation of their signaling pathways. Our findings also reveal that SPL is critical for 247R-triggered EGFR transactivation pathways. Thus SPL could be considered as a potentially novel target in α1aAR-mediated cardiovascular disorders.

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Stress Response of Nutrient-Starved Cardiovascular Cells

Handbook of Famine, Starvation, and Nutrient Deprivation ◽

10.1007/978-3-319-40007-5_23-1 ◽

2017 ◽

pp. 1-19

Author(s):

Lakshmi Pulakat ◽

Madhavi P. Gavini

Keyword(s):

Stress Response ◽

Cardiovascular Cells

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Sulfur Contents in Sulfonated Hyaluronic Acid Direct the Cardiovascular Cells Fate

ACS Applied Materials & Interfaces ◽

10.1021/acsami.0c15729 ◽

2020 ◽

Vol 12 (41) ◽

pp. 46827-46836

Author(s):

Yang Yu ◽

Shijie Zhu ◽

Yachen Hou ◽

Jingan Li ◽

Shaokang Guan

Keyword(s):

Hyaluronic Acid ◽

Cardiovascular Cells

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Role of pro renin receptor in cardiovascular cells from the aspect of signaling

Frontiers in Bioscience ◽

10.2741/e185 ◽

2010 ◽

Vol E2 (4) ◽

pp. 1246-1249 ◽

Cited By ~ 6

Author(s):

Hirofumi Hitom

Keyword(s):

Cardiovascular Cells

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Nuclear membrane receptors and channels as targets for drug development in cardiovascular diseasesThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-115 ◽

2009 ◽

Vol 87 (2) ◽

pp. 108-119 ◽

Cited By ~ 29

Author(s):

Ghassan Bkaily ◽

Levon Avedanian ◽

Danielle Jacques

Keyword(s):

Nuclear Membrane ◽

Membrane Receptors ◽

Heart Cells ◽

Ionic Homeostasis ◽

Life And Death ◽

Ionic Transporters ◽

Research Workshop ◽

Modulation Of Gene Expression ◽

Cardiovascular Cells ◽

G Protein Coupled

The use of confocal microscopy has shown that the nucleus plays an important role in excitation–contraction and excitation–secretion coupling of several excitable and nonexcitable cardiovascular cells. It has shown that the nuclear membranes, like the sarcolemmal membrane, possess ionic transporters as well as G protein-coupled receptors (GPCRs), which play a major role in modulating both cytosolic and nuclear ionic homeostasis and nuclear signalling. During spontaneous contraction of heart cells, the increase in cytosolic Ca2+ was immediately followed by a transient increase in nuclear Ca2+. The nuclear Ca2+ rise during excitation–contraction and excitation–secretion coupling was both dependent and independent of changes in cytosolic Ca2+. Nuclear membrane GPCRs, such as those of angiotensin II, neuropeptide Y, and ET-1, were functional and contributed to modulation of nuclear ionic homeostasis via direct and (or) indirect modulation of nuclear membrane ionic transporters such as channels, pumps, and exchangers. The signalling of nuclear membrane GPCRs may also contribute to modulation of gene expression, which may regulate proliferation and remodelling of cells and, indeed, life and death. Direct or indirect targeting of nuclear membrane ionic transporters and GPCRs may constitute a new target for drug action.

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