Posts Tagged: therapy

Acute Ischemic Stroke Therapy Overview

Acute Ischemic Stroke Therapy Overview

Luciana Catanese, Joseph Tarsia, Marc Fisher

A schematic representation of the cascade of ischemic injury over time. Courtesy of Dr Won-Ki Kim, Seoul Korea (Illustration Credit: Ben Smith). BBB indicates blood–brain barrier. [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]

Function and Therapeutic Potential of Noncoding RNAs in Cardiac Fibrosis

Function and Therapeutic Potential of Noncoding RNAs in Cardiac Fibrosis

Esther E. Creemers, Eva van Rooij

A model for the mechanisms of action of microRNAs (miRNAs) in cardiac fibrosis. Control of extracellular matrix (ECM) turnover in cardiac fibroblasts is mediated by at least 4 signaling cascades: TGFβ-SMADs, MAPK-p38, RhoA-actin dynamics-MRTF-A, and TRPC6-calcineurin. These pathways activate the transcription factors SMADs, SRF, and nuclear factor of activated T-cells (NFAT) on promoters of ECM-related genes to control its expression. The miRNAs targeting these genes are depicted in red. MiR-21* and miR-29 can be loaded into exosomes, secreted into the extracellular space, and taken up by other cell types of the heart to influence cardiac remodeling. AngII indicates angiotensin II; MAPK, mitogen-activated protein kinase; MRTF-A, myocardin-related transcription factor; RhoA, Ras homolog family member A; SRF, serum response factor; TGFβ, transforming growth factor-β; and TRPC6, transient receptor potential cation channel C6. (Illustration Credit: Ben Smith.) [Powerpoint File]

Heart Failure With Preserved Ejection Fraction: Mechanisms, Clinical Features, and Therapies

Heart Failure With Preserved Ejection Fraction: Mechanisms, Clinical Features, and Therapies

Kavita Sharma, David A. Kass

Schematic of myocardial abnormalities revealed in human heart failure with a preserved ejection fraction (HFpEF). The left side shows components of the β-adrenergic (β-AR) pathway from the receptor to adenyl cyclase (AC) and generation of cAMP to activation of protein kinase A (PKA). The latter is involved in the modification of L-type calcium channels (LTCC), phospholamban (PLN), titin, and other regulatory thin-filament proteins (eg, troponin I, TnI), which influence myofilament stiffness and contractile activation. Evidence suggests a deficiency in this signaling pathway in HFpEF, with increased titin stiffness and depressed β-AR responsiveness. The middle section shows transforming growth factor β (TGFβ)– and Gq-protein–coupled receptor (GqPR) signaling involving transcription factors (Smad), phospholipase C (PLC), and mitogen-activated kinases (MAPk), which are involved in the activation of profibrotic and hypertrophic cascades. At the right is the nitric oxide synthase (NOS) pathway resulting in nitric oxide (NO) activation of soluble guanylate cyclase (sGC), generation of cyclic guanosine monophosphate (cGMP), and activation of protein kinase G (PKG). In the middle is reactive oxygen species (ROS) activated by TGFβ-, β-AR-, and GqPR-coupled signaling, which inhibits the NOS-cGMP generation and thereby PKG activity, stimulates calcium–calmodulin activated kinase II (CamKII), which subsequently renders sarcoplasmic reticular (SR) calcium release by the ryanodine receptor (RyR2) more promiscuous. ROS and CamKII also impact titin to influence stiffening. Last, the upper right depicts the role of matrix modulation by cytokines/inflammation and the bidirectional interaction of these factors with the myocyte. IL indicates interleukin; SERCA, sarcoplasmic reticular ATPase; sST2, soluble ST2; and TNF, tumor necrosis factor. Illustration credit: Ben Smith. [Powerpoint File]

Heart Failure With Preserved Ejection Fraction: Mechanisms, Clinical Features, and Therapies

Heart Failure With Preserved Ejection Fraction: Mechanisms, Clinical Features, and Therapies

Kavita Sharma, David A. Kass

Schematic of the integrative physiology of heart failure with a preserved ejection fraction (HFpEF) showing various extracardiac mechanisms and how they are involved. From top left, counterclockwise: lung involvement including primary lung disease leading to pulmonary arterial hypertension, secondary pulmonary venous hypertension (PVH), impaired lung muscle mechanics, and eventual increased pulsatile right ventricular (RV) load; abdominal compartment mechanisms including splanchnic circulation (preload), bowel congestion leading to endotoxin translocation and systemic inflammation; skeletal muscle mechanisms including impaired metabolism and peripheral vasodilation; renal mechanisms including passive congestion leading to renal impairment, changes in neurohormonal axis activation, hypertension, abnormal fluid homeostasis, eventual oliguria/renal insufficiency; ventricular–vascular mechanisms including ventricular stiffening leading to systolic and diastolic impairment, diminished systolic reserve, increased cardiac energetic demands, and fluid-pressure shift sensitivity. Illustration credit: Ben Smith. [Powerpoint File]