Posts Tagged: heart failure

Preclinical Studies of Stem Cell Therapy for Heart Disease

Preclinical Studies of Stem Cell Therapy for Heart Disease

Bryon A. Tompkins, Wayne Balkan, Johannes Winkler, Mariann Gyöngyösi, Georg Goliasch, Francisco Fernández-Avilés, Joshua M. Hare

Different administration routes and cell types for the treatment of heart disease. The cell types listed under each delivery method refer only to those referenced (superscripted number) in this review. AdSC indicates adipose-derived stem cell; BM, bone marrow; CDC, cardiosphere-derived cell; CMG, cardiomyogenic cell; CSC, cardiac stem cell; DCM, dilated cardiomyopathy; iPSC, induced pluripotent stem cell; MI, myocardial infarction; MNC, mononuclear cell; MSC, mesenchymal stem cell; and UC, umbilical cord. Adapted from Golpanian et al166 with permission. Copyright ©2016, the American Physiological Society. [Powerpoint File]

Cardiovascular Effects of New Oral Glucose-Lowering Agents: DPP-4 and SGLT-2 Inhibitors

Cardiovascular Effects of New Oral Glucose-Lowering Agents: DPP-4 and SGLT-2 Inhibitors

André J. Scheen

Illustration of the primary mechanisms of action of DPP-4 (dipeptidyl peptidase-4) inhibitors and their GLP (glucagon-like peptide)-1–dependent and GLP-1–independent effects. Positive effects may be counterbalanced by unknown negative effects so that the final resulting is the absence of improvement of myocardial function. GIP indicates glucose-dependent insulinotropic polypeptide. [Powerpoint File]

 

Cardiovascular Effects of New Oral Glucose-Lowering Agents: DPP-4 and SGLT-2 Inhibitors

Cardiovascular Effects of New Oral Glucose-Lowering Agents: DPP-4 and SGLT-2 Inhibitors

André J. Scheen

Illustration of the primary mechanisms of action of SGLT-2 (sodium-glucose cotransporter type 2) inhibitors and their hemodynamic and metabolic effects resulting in improved myocardial function and a reduced risk of heart failure. [Powerpoint File]

Calcium Signaling and Reactive Oxygen Species in Mitochondria

Calcium Signaling and Reactive Oxygen Species in Mitochondria

Edoardo Bertero, Christoph Maack

Role of mitochondrial Ca2+ uptake for ATP production and reactive oxygen species (ROS) elimination. Ca2+ is released from the sarcoplasmic reticulum (SR) via ryanodine receptors type 2 (RyR2). Mitochondria take up Ca2+ via the mitochondrial Ca2+ uniporter (MCU) and release it via the Na+/Ca2+ Li+ permeable exchanger (NCLX). Slower SR Ca2+ release via inositol 1,4,5-trisphosphate receptors (IP3R) may be taken up into mitochondria via ryanodine receptors type 1 (RyR1). Close contact points between the SR and mitochondria are controlled by SR-located mitofusin 2 (Mfn2) tethering with Mfn2 and Mfn1 on the outer mitochondrial membrane (OMM), respectively, creating microdomains of high [Ca2+] in the vicinity of mitochondria. Another SR/mitochondrial tethering protein is FUN14 domain containing 1 (FUNDC1). In the matrix, Ca2+ activates Krebs cycle dehydrogenases to regenerate the reduced form of NADH (nicotamide adenine dinucleotide), which donates electrons to the respiratory chain. The electron flow produces a proton gradient (ΔpH) that drives ATP production at the F1Fo-ATP synthase (complex V). ATP converts creatine (Cr) to phosphocreatine (PCr) at the mitochondrial creatine kinase (CKm) while in the cytosol, PCr regenerates ADP at cytosolic CK (CKc). Superoxide (.O2−) is generated at complexes I and III of the respiratory chain and transformed to H2O2 by Mn2+-dependent superoxide dismutase (Mn-SOD). H2O2 is eliminated by glutathione peroxidase (GPX) and the peroxiredoxin (PRX)/thioredoxin (TRX) system. Reduced NADPH (nicotinamide adenine dinucleotide phosphate) regenerates glutathione (GSH) from its oxidized form (GSSG) via glutathione reductase (GR) and thioredoxin reductase (TR), respectively. NADPH is regenerated by isocitrate dehydrogenase (IDH), malic enzyme (MEP), and the nicotinamide nucleotide transhydrogenase (NNT). α-KG indicates α-ketoglutarate; IMM, inner mitochondrial membrane; I-V, complexes I-V of the respiratory chain; Q, Q-cycle; SERCA, SR Ca2+ ATPase; and TRXr/TRXo, reduced/oxidized TRX. Stars (*) denote the sites of Ca2+-induced activation. [Powerpoint File]

Calcium Signaling and Reactive Oxygen Species in Mitochondria

Calcium Signaling and Reactive Oxygen Species in Mitochondria

Edoardo Bertero, Christoph Maack

Mitochondrial calcium uniporter architecture and regulation. The mitochondrial Ca2+ uniporter (MCU) is a macromolecular complex composed of a pentamer of pore-forming subunits (MCUa) and several regulatory subunits. MCUa expression alone is not sufficient for reconstituting MCU activity, but coexpression of the essential MCU regulatory element (EMRE) is required. In the presence of low levels of Ca2+ in the intermembrane space (right half of the figure), the 2 paralogous EF-hand proteins MICU1 and MICU2 inhibit Ca2+ uptake. Vice versa, elevated Ca2+ induces structural rearrangements which enable Ca2+ influx into the mitochondrial matrix (left half of the figure). MCU regulator 1 (MCUR1) interacts with both MCUa and EMRE, but not with MICU1/MICU2, and acts as a scaffold factor for uniporter assembly. IMM indicates inner mitochondrial membrane. [Powerpoint File]

Sleep Apnea and Cardiovascular Disease: An Enigmatic Risk Factor

Sleep Apnea and Cardiovascular Disease: An Enigmatic Risk Factor

John S. Floras

Group mean gray matter differences in key cortical autonomic regions between individuals with and without obstructive sleep apnea (OSA). Cortical thickness (A) and voxel-based morphometric (B) analysis of 19 sex- and age-matched control (C) participants with no or mild OSA and 22 with moderate-to-severe OSA demonstrates, in the latter, significant thinning of the left dorsal posterior insular cortex (L dpIC) and thickening of the left midcingulate cortex (L MCC). L dpIC thinning correlated inversely with participants’ oxygen desaturation index; L MCC thickness correlated directly with muscle sympathetic burst incidence recorded with participants awake and resting supine (r=0.46; P=0.002). Reprinted from Taylor et al60 with permission. Copyright ©2017, Oxford University Press. [Powerpoint File]

Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity

Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity

Guanghong Jia, Michael A. Hill, James R. Sowers

The molecular proteins and signaling pathways in hyperglycemia- and insulin resistance-diabetic cardiomyopathy. Increased protein kinase C (PKC), mitogen-activated protein kinase (MAPK), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), sodium–glucose cotransporter-2 (SGLT2), O-linked N-acetylglucosamine (O-GlcNAc), and cyclic adenosine 5’-monophosphate-responsive element modulator (CREM) signaling, dysregulation of microRNA (miRNA) and exosomes, and reduction of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor (PPAR)-γ, and nuclear factor erythroid 2–related factor 2 (Nrf2) induce cardiac insulin resistance, subcellular component abnormalities, metabolic disorders, and structural changes, resulting in diabetic cardiomyopathy. [Powerpoint FIle]

Induced Pluripotent Stem Cells 10 Years Later For Cardiac Applications

Induced Pluripotent Stem Cells 10 Years Later: For Cardiac Applications

Yoshinori Yoshida, Shinya Yamanaka

Factors which possibly cause clonal differences of induced pluripotent stem cells (iPSCs). [Powerpoint File]

Induced Pluripotent Stem Cells 10 Years Later: For Cardiac Applications

Induced Pluripotent Stem Cells 10 Years Later: For Cardiac Applications

Yoshinori Yoshida, Shinya Yamanaka

Patient stratification based on drug responsiveness using induced pluripotent stem cells–derived cardiac myocytes. [Powerpoint File]

Contemporary Approaches to Modulating the Nitric Oxide–cGMP Pathway in Cardiovascular Disease

Contemporary Approaches to Modulating the Nitric Oxide–cGMP Pathway in Cardiovascular Disease

Jan R. Kraehling, William C. Sessa

Proteins and enzymes involved in the nitric oxide (NO)-nitric oxide–sensitive guanylate cyclase (NOsGC)–cGMP pathway and its modulators. Key players of the pathway are shown in blue, the positive modulators are shown in yellow, and the negative modulators in purple. Endothelial cells (EC) are shown in green (top), whereas the vascular smooth muscle cell (VSMC) is shown in red (bottom). The space between the 2 cells is called myoendothelial junction (MEJ). cGMP mediates its cellular functions through cGMP-modulated (cyclic nucleotide-gated [CNG]) cation channels, cGMP-dependent protein kinases (cGKs) and cGMP-regulated phosphodiesterases (PDEs). BH4 indicates tetrahydrobiopterin; CAV1, caveolin-1; CYB5R3, NADH-cytochrome b5 reductase 3; eNOS, endothelial nitric oxide synthase (NOS3); Hb2+/Hb3+, hemoglobin α (reduced/oxidized); and PDE, phosphodiesterase. [Powerpoint File]

Contemporary Approaches to Modulating the Nitric Oxide–cGMP Pathway in Cardiovascular Disease

Contemporary Approaches to Modulating the Nitric Oxide–cGMP Pathway in Cardiovascular Disease

Jan R. Kraehling, William C. Sessa

Mechanism of action of nitric oxide–sensitive guanylate cyclase (NOsGC) stimulators and activators. NOsGC stimulators bind to the enzyme and act in an allosteric manner. NO and NOsGC stimulators enhance the NOsGC activity synergistically. NOsGC activators occupy the heme binding site and work therefore only additively with NO. The oxidation of the heme-Fe2+ to heme-Fe3+ results in a weaker binding of heme to NOsGC, hence allowing the NOsGC activators to occupy the heme binding site easier. The schematic is derived from Zorn and Wells.111 [Powerpoint File]

Noninvasive Imaging in Adult Congenital Heart Disease

Noninvasive Imaging in Adult Congenital Heart Disease

Luke J. Burchill, Jennifer Huang, Justin T. Tretter, Abigail M. Khan, Andrew M. Crean, Gruschen R. Veldtman, Sanjiv Kaul, Craig S. Broberg

Three-dimensional (3D) echocardiographic quantification. In this example, left atrial and left ventricular volumes are measured using semiautomated border detection in a 3D echocardiogram. Ejection fraction can be derived without the geometric assumptions that limited 2D-derived measures, such as Simpson biplane and the area–length method. [Powerpoint File]

Noninvasive Imaging in Adult Congenital Heart Disease

Noninvasive Imaging in Adult Congenital Heart Disease

Luke J. Burchill, Jennifer Huang, Justin T. Tretter, Abigail M. Khan, Andrew M. Crean, Gruschen R. Veldtman, Sanjiv Kaul, Craig S. Broberg

Liver imaging in Fontan-associated liver disease. A, Contrast computed tomographic scan of upper abdomen in a patient with heterotaxy and a Fontan circulation demonstrating a well-circumscribed tumor measuring 5 cm in diameter in the right lobe of a midline liver (yellow asterix). B, Fluorodeoxyglucose-positron emission tomographic scan in the same patient demonstrating abnormal uptake in the right lobe of the liver in the region of the tumor. [Powerpoint File]

Current Interventional and Surgical Management of Congenital Heart Disease: Specific Focus on Valvular Disease and Cardiac Arrhythmias

Current Interventional and Surgical Management of Congenital Heart Disease: Specific Focus on Valvular Disease and Cardiac Arrhythmias

Kimberly A. Holst, Sameh M. Said, Timothy J. Nelson, Bryan C. Cannon, Joseph A. Dearani

Schematic representation of the possible lines of ablation to treat macro reentrant atrial tachycardia in the presence of various atrial anomalies associated with complex congenital heart disease. avn indicates atrioventricular node; CS, coronary sinus; FO, foramen ovale; HV, hepatic vein; IVC, inferior vena cava; LAA, left atrial appendage; LSVC, left superior vena cava; MV, mitral valve; PV, pulmonary valve; RAA, right atrial appendage; RSVC, right superior vena cava; TAPVR, total anomalous pulmonary venous return; and TV, tricuspid valve. Reproduced from Mavroudis et al53 with permission of the publisher. Copyright ©2008, The Society of Thoracic Surgeons. [Powerpoint File]

Cardioembolic Stroke

Cardioembolic Stroke

Hooman Kamel, Jeff S. Healey

Overlap among cryptogenic stroke, embolic stroke of undetermined source, and cardioembolic stroke. [Powerpiont File]