Posts Tagged: myocardium

Myocardial Viability: Survival Mechanisms and Molecular Imaging Targets in Acute and Chronic Ischemia

Myocardial Viability: Survival Mechanisms and Molecular Imaging Targets in Acute and Chronic Ischemia

Henry Gewirtz, Vasken Dilsizian

Diagrammatic representation of myocardial cell and potential targets of radiotracer imaging and mapping of the surface renin–angiotensin system. ACE indicates angiotensin-converting enzyme; AGT, angiotensinogen; Ang II, angiotensin II; AT1R, angiotensin II type 1 receptor; and AT2R, angiotensin II type 2 receptor. Reproduced with permission from Schindler and Dilsizian.61 Copyright © 2012, Elsevier. [Powerpoint File]

Myocardial Viability: Survival Mechanisms and Molecular Imaging Targets in Acute and Chronic Ischemia

Myocardial Viability: Survival Mechanisms and Molecular Imaging Targets in Acute and Chronic Ischemia

Henry Gewirtz, Vasken Dilsizian

Myocyte metabolic pathways outlined for glucose and fatty acid metabolism with focus on the mitochondrion. The electron transport chain (ETC), complexes I–V, is a series of proton pumps. The last of which, complex V, supplies protons to a proton-sensitive ATPase and thereby generates ATP. CPT1,2 indicates carnitine palmitoyltransferase 1,2; FA, fatty acid; PDH, pyruvate dehydrogenase; and TCA, tricarboxylic acid (Krebs cycle). Reproduced with permission from Huss and Kelly.30 Copyright © 2005, American Society for Clinical Investigation. [Powerpoint File]

Myocardial Viability: Survival Mechanisms and Molecular Imaging Targets in Acute and Chronic Ischemia

Myocardial Viability: Survival Mechanisms and Molecular Imaging Targets in Acute and Chronic Ischemia

Henry Gewirtz, Vasken Dilsizian

Key myocyte organelles and ion channels and their function under conditions of ischemia and reperfusion. Ischemia (left panel) causes influx of Ca2+ and decline in pH, both of which, if not severe, facilitate maintenance of closed mitochondrial permeability transition pore (mPTP). On reperfusion (right panel), key events include restoration of physiological pH, burst of reactive oxygen species (ROS) from mitochondria, release of Ca2+ from the sarcoplasmic reticulum (SR), and opening of mPTP which results in collapse of its Δψ. Reproduced with permission from Hausenloy and Yellon.27 Copyright © 2013, American Society for Clinical Investigation. [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]

Insulin Signaling and Heart Failure

Insulin Signaling and Heart Failure

Christian Riehle, E. Dale Abel

Schematic representation of insulin signaling pathway. Simplified summary of key elements involved in insulin signal transduction that ultimately regulate multiple cellular processes. On binding to its ligand, insulin and insulin-like growth factor-1 (IGF-1) receptors undergo autophosphorylation, which increases their tyrosine kinase activities. Tyrosine phosphorylation and activation of the docking proteins insulin receptor substrates 1 and 2 (IRS1/2), engages regulatory subunits of the phosphatidylinositol-3-kinase (PI3K) that generates phosphatidylinositol (3,4,5)-triphosphate (PIP3) from phosphatidylinositol 3,4, bisphosphate (PIP2). The serine threonine kinases phosphoinositide-dependent protein kinase 1 (PDPK1) and Akt1 or Akt2 bind to PIP3 by their PH domains. PDPK1 phosphorylates Akt on Thr 308, and mechanistic target of Rapamycin complex 2 (mTORC2) phosphorylates Akt1/2 on Ser 473. Once activated, Akt in turn phosphorylates multiple targets of which a subset is shown. Phosphorylation of these targets induces pleiotropic cellular responses: B-cell leukemia/lymphoma 2 (BCL-2) phosphorylation inhibits apoptosis, forkhead box O (FOXO) protein phosphorylation promotes nuclear exclusion, thereby repressing the expression of FOXO-regulated transcripts that mediate autophagy and apoptosis. Tuberous sclerosis complex (TSC) 1/2 phosphorylation promotes mTOR activation, which increases mRNA translation, promotes protein synthesis, cell growth, mitochondrial fusion, and also inhibits autophagy. Phosphorylation of glycogen synthase kinase (GSK) removes the repression of glycogen synthase, which in concert with increased availability of glucose promotes glycogen synthesis. Phosphorylation of endothelial nitric oxide synthase (NOSIII) or eNOS by Akt increases the generation of nitric oxide to promote vasodilation. Akt phosphorylation mediates the translocation of vesicles containing the GLUT4 glucose transporter, in part, by phosphorylating downstream targets such as AS160 (not shown), leading to increased glucose transport after insertion into the plasma membrane. Akt also mediates, in part, translocation of the fatty acid translocase CD36. Insulin signaling also promotes activation of the mitogen-activated protein kinases (extracellular-regulated kinase [ERK]1/2) to increase the expression of various genes. [Powerpoint File]

Insulin Signaling and Heart Failure

Insulin Signaling and Heart Failure

Christian Riehle, E. Dale Abel

Summary of mechanisms that lead to insulin resistance in heart failure or in the metabolic syndrome. Signaling events in skeletal muscle, liver, adipose tissue, and brain (not shown) impair insulin signaling in each respective organ leading to metabolic perturbations as illustrated, which alter the systemic milieu in ways that may adversely affect cardiac structure and function. [Powerpoint File]

Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps

Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps

Kathleen M. Broughton, Mark A. Sussman

Cardiac regenerative medicine product to marketplace. Several companies focused on the treatment of heart failure and regenerative cardiac medicine have emerged over the past decade. At this time, no commercially available product is approved by the US FDA and commercially available in the United States. Each company is positioned based on its most current clinical status in ClinicalTrials.gov and the company website. This figure was last updated on February 1, 2016. [Powerpoint File]

Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps

Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps

Kathleen M. Broughton, Mark A. Sussman

Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis of individual adult stems cells as a cardiovascular therapy. The analysis focus is the individual adult stem cell therapeutic treatment options. The analysis focuses on the internal workings of the individual treatment options based on current clinical trial results and ongoing preclinical research. [Powerpoint File]

Mechanotransduction in Cardiac Hypertrophy and Failure

Mechanotransduction in Cardiac Hypertrophy and Failure

Robert C. Lyon*, Fabian Zanella*, Jeffrey H. Omens, Farah Sheikh

A schematic representation of the specific protein complexes linked to sarcomere-mediated mechanotransduction and mechanotransmission in cardiac muscle. CnA indicates calcineurin A; CS-1, calsarcin-1; ECM, extracellullar matrix; ERK2, extracellular signal–regulated kinase-2; FHL1, four-and-a-half LIM domain protein 1; MARPs, muscle-specific ankyrin repeat proteins; MEK2, mitogen-activated protein kinase kinase-2; MLP, muscle-specific LIM domain protein; MURFs, muscle-specific RING-finger proteins; NBR1 indicates neighbor to BRCA1; N-RAP, nebulin-related anchoring protein; p62/SQSTM1, p62/sequestosome-1; PICOT, protein kinase C–interacting cousin of thioredoxin; RAF1, rapid accelerated fibrosarcoma-1; and TCAP, titin Cap (illustration credit: Ben Smith). [Powerpoint File]

Mechanotransduction in Cardiac Hypertrophy and Failure

Mechanotransduction in Cardiac Hypertrophy and Failure

Robert C. Lyon*, Fabian Zanella*, Jeffrey H. Omens, Farah Sheikh

A schematic representation of the specific protein complexes linked to cell–cell junction and sarcolemma-mediated mechanotransduction and mechanotransmission in cardiac muscle. Dotted arrows highlight cross-talk between integrin and caveolin, as well as integrin and the dystroglycan complex. α-CAT indicates α-catenin; β-CAT, β-catenin; CAR, coxsackievirus-associated receptor; CAS, p130 CRK-associated substrate; CAV3, caveolin-3; DSC2 indicates desmocollin-2; DSG2, desmoglein-2; DSP, desmoplakin; ECM, extracellullar matrix; FAK, focal adhesion kinase; ILK, integrin-linked kinase; JUP, plakoglobin; N-CAD, N-cadherin; PAX, paxilin; PKP2, plakophillin-2; and VIN, vinculin (illustration credit: Ben Smith). [Powerpoint File]

Cardiac Tissue Engineering: State of the Art

Cardiac Tissue Engineering: State of the Art

Marc N. Hirt, Arne Hansen, Thomas Eschenhagen

In vitro vascularization of 3-dimensional engineered tissues guided by micropatterns. A–E, Sequential generation of vascularized engineered tissue. A, Polydimethylsiloxane (PDMS) with microlanes was used as a substrate. B, After coating with collagen–chitosan hydrogel with or without angiogenic thymosin β4 (Tβ4) and (C) arteries and veins were isolated and placed on the 2 ends of the substrate. D, Three weeks later, capillary outgrowths connected and (E) cardiomyocytes were seeded onto the engineered vascular bed and cultured for additional 7 days to grow a beating, vascularized cardiac tissue. Reprinted from Chiu et al with permission of the publisher.58 F, Perfusion bioreactor for cell sheet technology. Triple-layer cell sheets were incubated on a cell-free collagen gel base with perfused microchannels (Ø=300 μm). The culture medium could diffuse into the collagen gel and provide oxygen and nutrients to the cell sheet. Endothelial cells in the cell sheets migrated into the collagen gel and finally connected with the microchannels. Reprinted from Sakaguchi et al with permission of the publisher.59 G, The alginate fiber vascularization technique applied to hydrogel-based engineered heart tissue (EHT). By dissolving alginate fibers with alginate lyase, microchannels were created and they endothelialized over time (here filled with air for better visualization). Reprinted from Vollert et al with permission of the publisher.39 [Powerpoint File]

Regulators of G-Protein Signaling in the Heart and Their Potential as Therapeutic Targets

Regulators of G-Protein Signaling in the Heart and Their Potential as Therapeutic Targets

Peng Zhang, Ulrike Mende

Regulation of G-protein–mediated signaling by RGS proteins. See text for detail on the G-protein activation/inactivation cycle. RGS proteins regulate G-protein–mediated signaling through (1) marked acceleration of Gα GTPase activity, which decreases both Gα- and Gβγ-mediated downstream effects, and (2) competition with downstream effectors for binding to activated Gα, which inhibits only Gα-mediated signal generation. Please note that this illustration depicts the traditional view of GPCR-induced, G-protein–mediated signal transduction. It does not incorporate GPCR-independent G-protein activation147 or G-protein–independent GPCR effects.148 Furthermore, full dissociation of Gα and Gβγ subunits may not be required to trigger downstream effects.149 [Powerpoint File]

Empowering Adult Stem Cells for Myocardial Regeneration

Empowering Adult Stem Cells for Myocardial Regeneration

Sadia Mohsin, Sailay Siddiqi, Brett Collins, Mark A. Sussman

Adult cardiac stem cell requires empowerment. Schematic representation of enhanced cardiac stem cells (CPCs) and their potentiation for repair to damaged myocardium relative to normal CPCs. [Powerpoint File]

Inflammation in Myocardial Diseases

Inflammation in Myocardial Diseases

David J. Marchant, John H. Boyd, David C. Lin, David J. Granville, Farshid S. Garmaroudi, Bruce M. McManus

Mechanisms by which ischemia and reperfusion (IR) induces inflammation. Phospholipase A2 (PLA2) activity results in elevated arachidonic acid (AA). AA can be metabolized by cyclooxygenases (COX), cytochromes p450 (CYP), and lipoxygenases (LOX) into prostaglandins, eicosanoids, or leukotrienes, respectively. IR-mediated reactive oxygen species (ROS) generation can result in the release of proteases and danger–associated molecular patterns (DAMPs) that can promote inflammation through the activation of nuclear factor (NF)-kB. Alternatively, ROS also leads to inflammasome activation which leads to further inflammatory cytokine production. (Illustration Credit: Cosmocyte/Ben Smith). PAR indicates protease-activated receptors; TLR, toll-like receptor; IL, interleukin; MyD88, myeloid differentiation primary response factor protein; EET, epoxyeicosatrienoic acids; HETE, hydroxyeicosatetraenoic acids; IKK, I kappa B kinase; PG, prostaglandin (Illustration credit: Cosmocyte/Ben Smith). [Powerpoint File]