Hao Wang1,2, Amit K Saha1, Xuming Sun1, Neal D Kon3, Carlos M Ferrario4, Leanne Groban1,2. 1. Department of Anesthesiology. 2. Department of Internal Medicine, Section of Molecular Medicine. 3. Department of Cardiothoracic Surgery. 4. Department of General Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina, USA.
Abstract
PURPOSE OF REVIEW: Hospitalizations for COVID-19 dramatically increase with age. This is likely because of increases in fragility across biological repair systems and a weakened immune system, including loss of the cardiorenal protective arm of the renin--angiotensin system (RAS), composed of angiotensin-converting enzyme-2 (ACE2)/angiotensin-(1--7) [Ang-(1--7)] and its actions through the Mas receptor. The purpose of this review is to explore how cardiac ACE2 changes with age, cardiac diseases, comorbid conditions and pharmaceutical regimens in order to shed light on a potential hormonal unbalance facilitating SARs-CoV-2 vulnerabilities in older adults. RECENT FINDINGS: Increased ACE2 gene expression has been reported in human hearts with myocardial infarction, cardiac remodeling and heart failure. We also found ACE2 mRNA in atrial appendage tissue from cardiac surgical patients to be positively associated with age, elevated by certain comorbid conditions (e.g. COPD and previous stroke) and increased in conjunction with patients' chronic use of antithrombotic agents and thiazide diuretics but not drugs that block the renin--angiotensin system. SUMMARY: Cardiac ACE2 may have bifunctional roles in COVID-19 as ACE2 not only mediates cellular susceptibility to SARS-CoV-2 infection but also protects the heart via the ACE2/Ang-(1--7) pathway. Linking tissue ACE2 from cardiac surgery patients to their comorbid conditions and medical regimens provides a unique latform to address the influence that altered expression of the ACE2/Ang-(1-7)/Mas receptor axis might have on SARs-CoV-2 vulnerability in older adults.
PURPOSE OF REVIEW: Hospitalizations for COVID-19 dramatically increase with age. This is likely because of increases in fragility across biological repair systems and a weakened immune system, including loss of the cardiorenal protective arm of the renin--angiotensin system (RAS), composed of angiotensin-converting enzyme-2 (ACE2)/angiotensin-(1--7) [Ang-(1--7)] and its actions through the Mas receptor. The purpose of this review is to explore how cardiac ACE2 changes with age, cardiac diseases, comorbid conditions and pharmaceutical regimens in order to shed light on a potential hormonal unbalance facilitating SARs-CoV-2 vulnerabilities in older adults. RECENT FINDINGS: Increased ACE2 gene expression has been reported in human hearts with myocardial infarction, cardiac remodeling and heart failure. We also found ACE2 mRNA in atrial appendage tissue from cardiac surgical patients to be positively associated with age, elevated by certain comorbid conditions (e.g. COPD and previous stroke) and increased in conjunction with patients' chronic use of antithrombotic agents and thiazide diuretics but not drugs that block the renin--angiotensin system. SUMMARY: Cardiac ACE2 may have bifunctional roles in COVID-19 as ACE2 not only mediates cellular susceptibility to SARS-CoV-2 infection but also protects the heart via the ACE2/Ang-(1--7) pathway. Linking tissue ACE2 from cardiac surgery patients to their comorbid conditions and medical regimens provides a unique latform to address the influence that altered expression of the ACE2/Ang-(1-7)/Mas receptor axis might have on SARs-CoV-2 vulnerability in older adults.
Authors: Mark W Tenforde; Erica Billig Rose; Christopher J Lindsell; Nathan I Shapiro; D Clark Files; Kevin W Gibbs; Matthew E Prekker; Jay S Steingrub; Howard A Smithline; Michelle N Gong; Michael S Aboodi; Matthew C Exline; Daniel J Henning; Jennifer G Wilson; Akram Khan; Nida Qadir; William B Stubblefield; Manish M Patel; Wesley H Self; Leora R Feldstein Journal: MMWR Morb Mortal Wkly Rep Date: 2020-07-03 Impact factor: 17.586
Authors: David Ellinghaus; Frauke Degenhardt; Luis Bujanda; Maria Buti; Agustín Albillos; Pietro Invernizzi; Javier Fernández; Daniele Prati; Guido Baselli; Rosanna Asselta; Marit M Grimsrud; Chiara Milani; Fátima Aziz; Jan Kässens; Sandra May; Mareike Wendorff; Lars Wienbrandt; Florian Uellendahl-Werth; Tenghao Zheng; Xiaoli Yi; Raúl de Pablo; Adolfo G Chercoles; Adriana Palom; Alba-Estela Garcia-Fernandez; Francisco Rodriguez-Frias; Alberto Zanella; Alessandra Bandera; Alessandro Protti; Alessio Aghemo; Ana Lleo; Andrea Biondi; Andrea Caballero-Garralda; Andrea Gori; Anja Tanck; Anna Carreras Nolla; Anna Latiano; Anna Ludovica Fracanzani; Anna Peschuck; Antonio Julià; Antonio Pesenti; Antonio Voza; David Jiménez; Beatriz Mateos; Beatriz Nafria Jimenez; Carmen Quereda; Cinzia Paccapelo; Christoph Gassner; Claudio Angelini; Cristina Cea; Aurora Solier; David Pestaña; Eduardo Muñiz-Diaz; Elena Sandoval; Elvezia M Paraboschi; Enrique Navas; Félix García Sánchez; Ferruccio Ceriotti; Filippo Martinelli-Boneschi; Flora Peyvandi; Francesco Blasi; Luis Téllez; Albert Blanco-Grau; Georg Hemmrich-Stanisak; Giacomo Grasselli; Giorgio Costantino; Giulia Cardamone; Giuseppe Foti; Serena Aneli; Hayato Kurihara; Hesham ElAbd; Ilaria My; Iván Galván-Femenia; Javier Martín; Jeanette Erdmann; Jose Ferrusquía-Acosta; Koldo Garcia-Etxebarria; Laura Izquierdo-Sanchez; Laura R Bettini; Lauro Sumoy; Leonardo Terranova; Leticia Moreira; Luigi Santoro; Luigia Scudeller; Francisco Mesonero; Luisa Roade; Malte C Rühlemann; Marco Schaefer; Maria Carrabba; Mar Riveiro-Barciela; Maria E Figuera Basso; Maria G Valsecchi; María Hernandez-Tejero; Marialbert Acosta-Herrera; Mariella D'Angiò; Marina Baldini; Marina Cazzaniga; Martin Schulzky; Maurizio Cecconi; Michael Wittig; Michele Ciccarelli; Miguel Rodríguez-Gandía; Monica Bocciolone; Monica Miozzo; Nicola Montano; Nicole Braun; Nicoletta Sacchi; Nilda Martínez; Onur Özer; Orazio Palmieri; Paola Faverio; Paoletta Preatoni; Paolo Bonfanti; Paolo Omodei; Paolo Tentorio; Pedro Castro; Pedro M Rodrigues; Aaron Blandino Ortiz; Rafael de Cid; Ricard Ferrer; Roberta Gualtierotti; Rosa Nieto; Siegfried Goerg; Salvatore Badalamenti; Sara Marsal; Giuseppe Matullo; Serena Pelusi; Simonas Juzenas; Stefano Aliberti; Valter Monzani; Victor Moreno; Tanja Wesse; Tobias L Lenz; Tomas Pumarola; Valeria Rimoldi; Silvano Bosari; Wolfgang Albrecht; Wolfgang Peter; Manuel Romero-Gómez; Mauro D'Amato; Stefano Duga; Jesus M Banales; Johannes R Hov; Trine Folseraas; Luca Valenti; Andre Franke; Tom H Karlsen Journal: N Engl J Med Date: 2020-06-17 Impact factor: 91.245
Authors: Anuradha Lala; Kipp W Johnson; James L Januzzi; Adam J Russak; Ishan Paranjpe; Felix Richter; Shan Zhao; Sulaiman Somani; Tielman Van Vleck; Akhil Vaid; Fayzan Chaudhry; Jessica K De Freitas; Zahi A Fayad; Sean P Pinney; Matthew Levin; Alexander Charney; Emilia Bagiella; Jagat Narula; Benjamin S Glicksberg; Girish Nadkarni; Donna M Mancini; Valentin Fuster Journal: J Am Coll Cardiol Date: 2020-06-08 Impact factor: 24.094
Authors: Stephen W Bickler; David M Cauvi; Kathleen M Fisch; James M Prieto; Alicia G Sykes; Hariharan Thangarajah; David A Lazar; Romeo C Ignacio; Dale R Gerstmann; Allen F Ryan; Philip E Bickler; Antonio De Maio Journal: BMC Med Genomics Date: 2021-05-24 Impact factor: 3.063
Authors: Carlos M Ferrario; Jessica L VonCannon; Jie Zhang; Jorge P Figueroa; Kendra N Wright; Leanne Groban; Amit Saha; J Wayne Meredith; Sarfaraz Ahmad Journal: Peptides Date: 2021-12-18 Impact factor: 3.750