Posts Tagged: cardiomyopathy

Calcium Signaling and Cardiac Arrhythmias

Calcium Signaling and Cardiac Arrhythmias

Andrew P. Landstrom, Dobromir Dobrev, Xander H.T. Wehrens

Ryanodine receptor type-2 (RyR2) macromolecular complex. Cartoon representing RyR2 pore-forming subunits with accessory proteins that bind to and/or modulate channel function. CaM indicates calmodulin; CaMKII, Ca2+/calmodulin-dependent protein kinase II; CASQ2, calsequestrin-2; FKBP12.6, FK506-binding protein-12.6; JCTN, junctin; JPH2, juncophilin-2; PKA, protein kinase A; PM, plasma membrane; PP, protein phosphatase; SR, sarcoplasmic reticulum; TECRL, trans-2,3-enoyl-CoA reductase-like protein; and TRDN; triadin. [Powerpoint File]

Calcium Signaling and Cardiac Arrhythmias

Calcium Signaling and Cardiac Arrhythmias

Andrew P. Landstrom, Dobromir Dobrev, Xander H.T. Wehrens

Role of calcium-handling in excitation–contraction (EC) coupling. A, Schematic overview of key Ca2+-handling proteins involved in EC coupling. B, Schematic diagram of Ca2+ release unit and major components of the JMC (junctional membrane complex). The transverse tubule (TT) and sarcoplasmic reticulum (SR) membranes approximate to form the dyad. BIN1 indicates bridging integrator 1; Cav1.2, L-type Ca2+ channel; CAV3, caveolin-3; JPH2, juncophilin-2; NCX1, Na+/Ca2+ exchanger type-1; PM, plasma membrane; PMCA, plasmalemmal Ca2+-ATPase; RyR2, ryanodine receptor type-2; and SERCA2a, sarco/endoplasmic reticulum ATPase type-2a.* [Powerpoint File]

Heart–Brain Axis: Effects of Neurologic Injury on Cardiovascular Function

Heart–Brain Axis: Effects of Neurologic Injury on Cardiovascular Function

Pouya Tahsili-Fahadan, Romergryko G. Geocadin

Neural control of the cardiovascular system. Afferent and efferent pathways are shown in green and red lines, respectively. Some potential sites for therapeutic interventions are illustrated in the blue text boxes. The figure has been simplified to illustrate the major cortical, subcortical, and brain stem areas involved in control of the cardiovascular function. Most of the shown areas are interconnected. For anatomic details and physiological effects of the illustrated pathways, please refer to the text. [Powerpoint File]

T1 Mapping in Characterizing Myocardial Disease: A Comprehensive Review

T1 Mapping in Characterizing Myocardial Disease: A Comprehensive Review

Valentina O. Puntmann, Elif Peker, Y. Chandrashekhar, Eike Nagel

Understanding the differences between ischemic heart disease and nonischemic cardiomyopathy. In ischemic heart disease, myocardial injury occurs via atherothrombotic event, such as acute myocardial infarction, a symptomatic clinical event, characterized by central crushing chest pain, shortness of breath, and ischemic ECG changes. Postinfarction left ventricular (LV) remodeling is a result of an acute loss of myocardium, leading to an abrupt increase in loading conditions that induces a unique pattern of remodeling involving the infarcted border zone and remote noninfarcted myocardium.119,120 On the contrary, nonischemic ventricular remodeling is characterized by a protracted subclinical course ahead of the onset of symptoms in an advanced stage of disease and functional impairment. Typical triggers include genetic, systemic of external noci, which affect myocardium globally. The remodeling is underscored by the several complex interstitial processes which lead to extracellular matrix (ECM) remodeling, and intrinsic myocardial impairment.9 LGE indicates late gadolinium enhancement. [Powerpoint File]

Mechanical Regulation of Cardiac Aging in Model Systems

Mechanical Regulation of Cardiac Aging in Model Systems

Ayla O. Sessions, Adam J. Engler

Physiological vs pathological age–related changes of the sarcomere and intercalated disc (ID). Schematic representation of sarcomere and ID components in the cardiomyocyte implicated in physiological aging (red, upregulated; green, downregulated), pathological aging (yellow, upregulated; blue, downregulated), or yet undetermined (black). Arrows to nucleus indicate translocation of protein into the nucleus with age. α-CAT indicates α-catenin; ACTN1, α-actinin-1; α-MHC, α-myosin heavy chain; β-CAT, β-catenin; c-TnT4, cardiac troponin T-4; F-actin, filamentous actin; MLP, muscle-binding limb protein; N-CAD, N-cadherin; P-MLC-2, phosphorylated myosin light chain-2; and Vinc, vinculin. [Powerpoint File]

Mechanical Regulation of Cardiac Aging in Model Systems

Mechanical Regulation of Cardiac Aging in Model Systems

Ayla O. Sessions, Adam J. Engler

Physiological vs pathological age–related changes of costamere and extracellular matrix (ECM). Schematic representation of Costamere and ECM of the cardiomyocyte implicated in physiological aging (red, upregulated; green, downregulated), pathological aging (yellow, upregulated; blue, downregulated), or yet undetermined (black). Stripes of 2 colors indicate lack of consensus on expression levels across species or involvement in physiological vs pathological aging. α7 indicates α7-integrin; β1, β1-integrin; ACTN1, α-actinin-1; AGE’s, advanced glycosylation endproducts; Col I, collagen type 1; Col IV, collagen type IV; F-actin, filamentous actin; ID, intercalated disc; ILK, integrin-linked kinase; MMP2, matrix mettaloproteinase-2; MMP9, matrix metalloproteinase-9; MMP14, matrix metalloproteinase-14; and Vinc, vinculin. [Powerpoint File]

Heart Failure Compendium: Emerging Paradigms in Cardiomyopathies Associated With Cancer Therapies

Heart Failure Compendium: Emerging Paradigms in Cardiomyopathies Associated With Cancer Therapies

Bonnie Ky, Pimprapa Vejpongsa, Edward T.H. Yeh, Thomas Force, Javid J. Moslehi

Angiogenesis inhibitors (vascular endothelial growth factor [VEGF] signaling pathway [VSP] inhibitors) being tested in human cancer trials. Although these agents are being referred to as VSP inhibitors, drugs such as sunitinib inhibit many other receptor tyrosine kinases, allowing them to be approved for the treatment of other cancers while, at the same time, creating the possibility for a wide range of off-target toxicities. FDA indicates Food and Drug Administration; HIF, hypoxia-inducible factor; PDGF, platelet-derived growth factor; PDGFR, PDGF receptor; TKI, tyrosine kinase inhibitor; and VEGFR, VEGF receptor. (Illustration Credit: Ben Smith.) [Powerpoint File]

Heart Failure Compendium: Emerging Paradigms in Cardiomyopathies Associated With Cancer Therapies

Heart Failure Compendium: Emerging Paradigms in Cardiomyopathies Associated With Cancer Therapies

Bonnie Ky, Pimprapa Vejpongsa, Edward T.H. Yeh, Thomas Force, Javid J. Moslehi

Novel Food and Drug Administration (FDA)–approved and investigational human epidermal growth factor receptor-2 (HER2)–targeted agents being used for the treatment of breast cancer. EGF indicates endothelial growth factor; HB-EGF, heparin-binding EGF; NRG, neuregulins; TGF-α, transforming growth factor α; and TKI, tyrosine kinase inhibitor. (Illustration Credit: Ben Smith.) [Powerpoint File]

The Cardiac Desmosome and Arrhythmogenic Cardiomyopathies: From Gene to Disease

The Cardiac Desmosome and Arrhythmogenic Cardiomyopathies: From Gene to Disease

Mario Delmar, William J. McKenna

Desmosomal structure. Interaction between the desmosomal components at the intercellular junction is represented schematically in a and superimposed on an electron micrograph in b. Transmembrane desmosomal cadherins, DSG and DSC, bind the armadillo family proteins JUP and PKP, which in turn anchor the plakin family member DSP. The cytoplasmic plaque, which is further stabilized by lateral interactions among these proteins, anchors the intermediate filament cytoskeleton to the desmosome. Adapted from Green and Simpson9 with permission from MacMillan Publishers Ltd. [Powerpoint File]

The Genomic Architecture of Sporadic Heart Failure

The Genomic Architecture of Sporadic Heart Failure

Gerald W. Dorn II

Postulated effects of common polymorphisms on neurohormonal activation in heart failure. Schematic representation of neurohormonal signaling in heart failure. Myocardial injury in the form of cardiac damage or hemodynamic stress compromises forward cardiac output, activating compensatory increases in renin-angiotensin-aldosterone system (RAAS) and catecholamine release from sympathetic nerves. Angiotensin-converting enzyme (ACE) DD genotype increases ACE expression, and CLCNKA Gly83 may prime renin secretion, thus magnifying the RAAS response and causing reactive left ventricular hypertrophy with secondary myocardial impairment. The deletion polymorphism of presynaptic α1c adrenergic receptors increases norepinephrine release from sympathetic nerves, and the Arg 389 variant of myocardial β1-adrenergic receptors increases receptor signaling. Both effects sensitize the heart to catecholaminergic toxicity. Opposing these effects is the Leu41 gain-of-function GRK5 polymorphism that accelerates β-receptor desensitization. (Illustration by Cosmocyte/Ben Smith). [Powerpoint File]

Drosophila, Genetic Screens, and Cardiac Function

Drosophila, Genetic Screens, and Cardiac Function

Matthew J. Wolf, Howard A. Rockman

The embryonic and adult Drosophila circulatory system. A, The developing embryonic circulatory system arises from cardial precursor cells that migrate to form the dorsal vessel at Stage 16. Stages 12, 13, and 17 are shown. The figure is adapted from Fly Embryo RNAi Project (http://flyembryo.nhlbi.nih.gov). B, The adult fly circulatory system consists of an open system with the main conical chamber, heart, located along the dorsal aspect of the A1 abdominal segment. Suspensory muscles including the alary and ventral longitudinal muscle, also referred to as the dorsal diaphragm. Pericardial cells are closely juxtaposed along the length of the abdominal portion of the circulatory system. The figure is adapted from that of Miller.72 A 1-mm scale bar is shown for comparison. [Powerpoint File]

Caenorhabditis elegans Muscle: A Genetic and Molecular Model for Protein Interactions in the Heart

Caenorhabditis elegans Muscle: A Genetic and Molecular Model for Protein Interactions in the Heart

Guy M. Benian, Henry F. Epstein

Comparison of normal localization of C elegans twitchin and mouse myosin-binding protein C (MyBP-C). A, C elegans body wall muscle immunostained with antibodies to twitchin. Twitchin is localized to most of the A-band, except for the central portion (indicated by arrow). (Reprinted with permission of Rockefeller University Press from Benian GM, Tinley TL, Tang X, Borodovsky M. The C elegans gene unc-89, required for muscle M-line assembly, encodes a giant modular protein containing Ig and signal transduction domains. J Cell Biology. 1996;132:835–848.) B, Myocardium from a heart of a transgenic mouse expressing myc-tagged MyBP-C, and immunostained with anti-myc. This pattern of localization is similar to localization of endogenous MyBP-C: the protein is localized to much of the A-band, except for the central portion (indicated by arrow). (Reprinted with permission of the American Society for Clinical Investigation from Yang Q, Sanbe A, Osinska H, Hewett TE, Klevitsky R, Robbins J. A mouse model of myosin binding protein C human familial hypertrophic cardiomyopathy. J Clin Invest. 1998;102:1292–1300.) [Powerpoint File]

Interplay Between Heart and Skeletal Muscle Disease in Heart Failure

Interplay Between Heart and Skeletal Muscle Disease in Heart Failure: The 2011 George E. Brown Memorial Lecture

Elizabeth M. McNally, Jeffery A. Goldstein

Architecture of striated muscle. Sarcomeres are arranged in series and in parallel, flanked by Z lines. Costameres are the sarcolemma-associated structures where the Z lines efface the plasma membrane. The dystrophin complex is enriched at costameres and provides an attachment to the extracellular matrix. [Powerpoint File]