Emerging therapeutic targets for cardiac hypertrophy

被引:22
作者
Winkle, Alexander J. [1 ,2 ]
Nassal, Drew M. [1 ,2 ]
Shaheen, Rebecca [1 ,2 ]
Thomas, Evelyn [1 ,2 ]
Mohta, Shivangi [1 ,2 ]
Gratz, Daniel [1 ,2 ]
Weinberg, Seth H. [1 ,2 ]
Hund, Thomas J. [1 ,2 ,3 ]
机构
[1] Ohio State Univ, Wexner Med Ctr, Dorothy M Davis Heart & Lung Res Inst, Frick Ctr Heart Failure & Arrhythmia, Columbus, OH 43210 USA
[2] Ohio State Univ, Coll Engn, Dept Biomed Engn, Columbus, OH USA
[3] Ohio State Univ, Coll Med, Dept Internal Med, Wexner Med Ctr, Columbus, OH 43210 USA
基金
美国国家卫生研究院;
关键词
Hypertrophy; heart failure; spectrin; STAT3; CaMKII; computer modeling; FOCAL ADHESION KINASE; LEFT-VENTRICULAR HYPERTROPHY; PRESSURE-OVERLOAD; HEART-FAILURE; SIGNAL TRANSDUCER; MYOCARDIAL HYPERTROPHY; DILATED CARDIOMYOPATHY; GENETIC INHIBITION; CALCINEURIN PLAYS; TRANSCRIPTION;
D O I
10.1080/14728222.2022.2031974
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction Cardiac hypertrophy is associated with adverse outcomes across cardiovascular disease states. Despite strides over the last three decades in identifying molecular and cellular mechanisms driving hypertrophy, the link between pathophysiological stress stimuli and specific myocyte/heart growth profiles remains unclear. Moreover, the optimal strategy for preventing pathology in the setting of hypertrophy remains controversial. Areas Covered This review discusses molecular mechanisms underlying cardiac hypertrophy with a focus on factors driving the orientation of myocyte growth and the impact on heart function. We highlight recent work showing a novel role for the spectrin-based cytoskeleton, emphasizing regulation of myocyte dimensions but not hypertrophy per se. Finally, we consider opportunities for directing the orientation of myocyte growth in response to hypertrophic stimuli as an alternative therapeutic approach. Relevant publications on the topic were identified through Pubmed with open-ended search dates. Expert Opinion To define new therapeutic avenues, more precision is required when describing changes in myocyte and heart structure/function in response to hypertrophic stimuli. Recent developments in computational modeling of hypertrophic networks, in concert with more refined experimental approaches will catalyze translational discovery to advance the field and further our understanding of cardiac hypertrophy and its relationship with heart disease.
引用
收藏
页码:29 / 40
页数:12
相关论文
共 114 条
[1]   Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy [J].
Akhter, SA ;
Luttrell, LM ;
Rockman, HA ;
Iaccarino, G ;
Lefkowitz, RJ ;
Koch, WJ .
SCIENCE, 1998, 280 (5363) :574-577
[2]   CaMKII in myocardial hypertrophy and heart failure [J].
Anderson, Mark E. ;
Brown, Joan Heller ;
Bers, Donald M. .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2011, 51 (04) :468-473
[3]   Metabolic mechanisms in heart failure [J].
Ashrafian, Houman ;
Frenneaux, Michael P. ;
Opie, Lionel H. .
CIRCULATION, 2007, 116 (04) :434-448
[4]   The δ isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload [J].
Backs, Johannes ;
Backs, Thea ;
Neef, Stefan ;
Kreusser, Michael M. ;
Lehmann, Lorenz H. ;
Patrick, David M. ;
Grueter, Chad E. ;
Qi, Xiaoxia ;
Richardson, James A. ;
Hill, Joseph A. ;
Katus, Hugo A. ;
Bassel-Duby, Rhonda ;
Maier, Lars S. ;
Olson, Eric N. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (07) :2342-2347
[5]   Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies [J].
Bernardo, Bianca C. ;
Weeks, Kate L. ;
Pretorius, Lynette ;
McMullen, Julie R. .
PHARMACOLOGY & THERAPEUTICS, 2010, 128 (01) :191-227
[6]   Histone deacetylase inhibition in the treatment of heart disease [J].
Berry, Jeff M. ;
Cao, Dian J. ;
Rothermel, Beverly A. ;
Hill, Joseph A. .
EXPERT OPINION ON DRUG SAFETY, 2008, 7 (01) :53-67
[7]   A peptide of the amino-terminus of GRK2 induces hypertrophy and yet elicits cardioprotection after pressure overload [J].
Bledzka, Kamila M. ;
Manaserh, Iyad H. ;
Grondolsky, Jessica ;
Pfleger, Jessica ;
Roy, Rajika ;
Gao, Erhe ;
Chuprun, J. Kurt ;
Koch, Walter J. ;
Schumacher, Sarah M. .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2021, 154 :137-153
[8]   Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control [J].
Borghetti, Giulia ;
von Lewinski, Dirk ;
Eaton, Deborah M. ;
Sourij, Harald ;
Houser, Steven R. ;
Wallner, Markus .
FRONTIERS IN PHYSIOLOGY, 2018, 9
[9]   Melusin, a muscle-specific integrin β1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload [J].
Brancaccio, M ;
Fratta, L ;
Notte, A ;
Hirsch, E ;
Poulet, R ;
Guazzone, S ;
De Acetis, M ;
Vecchione, C ;
Marino, G ;
Altruda, F ;
Silengo, L ;
Tarone, G ;
Lembo, G .
NATURE MEDICINE, 2003, 9 (01) :68-75
[10]   Cardiotrophin-1 can protect cardiac myocytes from injury when added both prior to simulated ischaemia and at reoxygenation [J].
Brar, BK ;
Stephanou, A ;
Liao, ZH ;
O'Leary, RM ;
Pennica, D ;
Yellon, DM ;
Latchman, DS .
CARDIOVASCULAR RESEARCH, 2001, 51 (02) :265-274