Therapeutic Potential of Senolytics in Cardiovascular Disease

被引:43
作者
Dookun, Emily [1 ]
Passos, Joao F. [2 ]
Arthur, Helen M. [1 ]
Richardson, Gavin D. [1 ]
机构
[1] Newcastle Univ, Biosci Inst, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England
[2] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA
基金
英国生物技术与生命科学研究理事会;
关键词
Cardiovascular; Senescence; Senolytic; Inflammation; Remodelling; Atherosclerosis; CELLULAR SENESCENCE; SECRETORY PHENOTYPE; HEART-FAILURE; BCL-2; FAMILY; STEM-CELLS; MORTALITY; DIGOXIN; ATHEROSCLEROSIS; REGENERATION; TELOMERASE;
D O I
10.1007/s10557-020-07075-w
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Ageing is the biggest risk factor for impaired cardiovascular health, with cardiovascular disease being the leading cause of death in 40% of individuals over 65 years old. Ageing is associated with both an increased prevalence of cardiovascular disease including heart failure, coronary artery disease, and myocardial infarction. Furthermore, ageing is associated with a poorer prognosis to these diseases. Genetic models allowing the elimination of senescent cells revealed that an accumulation of senescence contributes to the pathophysiology of cardiovascular ageing and promotes the progression of cardiovascular disease through the expression of a proinflammatory and profibrotic senescence-associated secretory phenotype. These studies have resulted in an effort to identify pharmacological therapeutics that enable the specific elimination of senescent cells through apoptosis induction. These senescent cell apoptosis-inducing compounds are termed senolytics and their potential to ameliorate age-associated cardiovascular disease is the focus of this review.
引用
收藏
页码:187 / 196
页数:10
相关论文
共 97 条
  • [1] Stem Cell Therapy in Heart Diseases: A Review of Selected New Perspectives, Practical Considerations and Clinical Applications
    Abdelwahid, Eltyeb
    Siminiak, Tomasz
    Cesar Guarita-Souza, Luiz
    Athayde Teixeira de Carvalho, Katherine
    Gallo, Pasquale
    Shim, Winston
    Condorelli, Gianluigi
    [J]. CURRENT CARDIOLOGY REVIEWS, 2011, 7 (03) : 201 - 212
  • [2] A complex secretory program orchestrated by the inflammasome controls paracrine senescence
    Acosta, Juan Carlos
    Banito, Ana
    Wuestefeld, Torsten
    Georgilis, Athena
    Janich, Peggy
    Morton, Jennifer P.
    Athineos, Dimitris
    Kang, Tae-Won
    Lasitschka, Felix
    Andrulis, Mindaugas
    Pascual, Gloria
    Morris, Kelly J.
    Khan, Sadaf
    Jin, Hong
    Dharmalingam, Gopuraja
    Snijders, Ambrosius P.
    Carroll, Thomas
    Capper, David
    Pritchard, Catrin
    Inman, Gareth J.
    Longerich, Thomas
    Sansom, Owen J.
    Aznar Benitah, Salvador
    Zender, Lars
    Gil, Jesus
    [J]. NATURE CELL BIOLOGY, 2013, 15 (08) : 978 - U221
  • [3] Natural regulatory T cells control the development of atherosclerosis in mice
    Ait-Oufella, H
    Salomon, BL
    Potteaux, S
    Robertson, AKL
    Gourdy, P
    Zoll, J
    Merval, R
    Esposito, B
    Cohen, JL
    Fisson, S
    Flavell, RA
    Hansson, GK
    Klatzmann, D
    Tedgui, A
    Mallat, Z
    [J]. NATURE MEDICINE, 2006, 12 (02) : 178 - 180
  • [4] Length-independent telomere damage drives post-mitotic cardiomyocyte senescence
    Anderson, Rhys
    Lagnado, Anthony
    Maggiorani, Damien
    Walaszczyk, Anna
    Dookun, Emily
    Chapman, James
    Birch, Jodie
    Salmonowicz, Hanna
    Ogrodnik, Mikolaj
    Jurk, Diana
    Proctor, Carole
    Correia-Melo, Clara
    Victorelli, Stella
    Fielder, Edward
    Berlinguer-Palmini, Rolando
    Owens, Andrew
    Greaves, Laura C.
    Kolsky, Kathy L.
    Parini, Angelo
    Douin-Echinard, Victorine
    Lebrasseur, Nathan K.
    Arthur, Helen M.
    Tual-Chalot, Simon
    Schafer, Marissa J.
    Roos, Carolyn M.
    Miller, Jordan D.
    Robertson, Neil
    Mann, Jelena
    Adams, Peter D.
    Tchkonia, Tamara
    Kirkland, James L.
    Mialet-Perez, Jeanne
    Richardson, Gavin D.
    Passos, Joao F.
    [J]. EMBO JOURNAL, 2019, 38 (05)
  • [5] Mechanisms driving the ageing heart
    Anderson, Rhys
    Richardson, Gavin D.
    Passos, Joao F.
    [J]. EXPERIMENTAL GERONTOLOGY, 2018, 109 : 5 - 15
  • [6] Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging
    Baar, Marjolein P.
    Brandt, Renata M. C.
    Putavet, Diana A.
    Klein, Julian D. D.
    Derks, Kasper W. J.
    Bourgeois, Benjamin R. M.
    Stryeck, Sarah
    Rijksen, Yvonne
    van Willigenburg, Hester
    Feijtel, Danny A.
    van der Pluijm, Ingrid
    Essers, Jeroen
    van Cappellen, Wiggert A.
    van IJcken, Wilfred F.
    Houtsmuller, Adriaan B.
    Pothof, Joris
    de Bruin, Ron W. F.
    Madl, Tobias
    Hoeijmakers, Jan H. J.
    Campisi, Judith
    de Keizer, Peter L. J.
    [J]. CELL, 2017, 169 (01) : 132 - +
  • [7] Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
    Baker, Darren J.
    Childs, Bennett G.
    Durik, Matej
    Wijers, Melinde E.
    Sieben, Cynthia J.
    Zhong, Jian
    Saltness, Rachel A.
    Jeganathan, Karthik B.
    Verzosa, Grace Casaclang
    Pezeshki, Abdulmohammad
    Khazaie, Khashayarsha
    Miller, Jordan D.
    van Deursen, Jan M.
    [J]. NATURE, 2016, 530 (7589) : 184 - +
  • [8] Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
    Baker, Darren J.
    Wijshake, Tobias
    Tchkonia, Tamar
    LeBrasseur, Nathan K.
    Childs, Bennett G.
    van de Sluis, Bart
    Kirkland, James L.
    van Deursen, Jan M.
    [J]. NATURE, 2011, 479 (7372) : 232 - U112
  • [9] Seno-destructive smooth muscle cells in the ascending aorta of patients with bicuspid aortic valve disease
    Balint, Brittany
    Yin, Hao
    Nong, Zengxuan
    Arpino, John-Michael
    O'Neil, Caroline
    Rogers, Stephanie R.
    Randhawa, Varinder K.
    Fox, Stephanie A.
    Chevalier, Jacqueline
    Lee, Jason J.
    Chu, Michael W. A.
    Pickering, J. Geoffrey
    [J]. EBIOMEDICINE, 2019, 43 : 54 - 66
  • [10] Dynamics of Cell Generation and Turnover in the Human Heart
    Bergmann, Olaf
    Zdunek, Sofia
    Felker, Anastasia
    Salehpour, Mehran
    Alkass, Kanar
    Bernard, Samuel
    Sjostrom, Staffan L.
    Szewczykowska, Mirosawa
    Jackowska, Teresa
    dos Remedios, Cris
    Malm, Torsten
    Andrae, Michaela
    Jashari, Ramadan
    Nyengaard, Jens R.
    Possnert, Goran
    Jovinge, Stefan
    Druid, Henrik
    Frisen, Jonas
    [J]. CELL, 2015, 161 (07) : 1566 - 1575