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Molecular Changes in Heart Failure

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Heart Failure

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Abstract

Heart failure is an increasingly prevalent cause of significant worldwide morbidity, mortality, and economic burden. Molecular investigations are unraveling the gene expression changes, protein signaling networks, and intercellular interactions that are causes and consequences of cardiac hypertrophy and failure. In particular, reactivation of the “fetal gene program” that is silenced in the normal adult heart has come to define the pathologic hypertrophic cardiac response that leads to heart failure. Our evolving knowledge of the molecular and cellular changes in the failed myocardium—for example, alterations in calcium signaling—is leading to new therapeutic options. This chapter summarizes some of the current understanding of changes responsible for cardiac hypertrophy, cardiomyocyte death, and altered cardiac metabolism. It also discusses emerging biomarkers for profiling of heart failure severity.

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Abbreviations

AKAP:

A-kinase anchoring protein

ANF :

Atrial natriuretic factor

AT:

Angiotensin

βMHC:

β-myosin heavy chain

BAD :

Bcl-2-antagonist of cell death

BNP :

Brain-type natriuretic peptide

cGMP:

Cyclic guanine monophosphate

CHF:

Congestive heart failure

CRP:

C-reactive protein

DAG:

Diacylglycerol

DISC:

Death-induced signaling complex

ECM:

Extracellular matrix

ERAD:

Endoplasmic reticulum-associated degradation

ERK:

Extracellular-signal-related kinase

FAK :

Focal adhesion kinase

Gab :

Grb2-associated binder

GSK3β :

Glycogen synthase kinase 3β

HSP :

Heat shock protein

ILK:

Integrin-linked kinase

IP3 :

Inositol triphosphate

LCAD:

Long-chain acyl-CoA dehydrogenase

LTCC:

L-type calcium channel

LVAD:

Left ventricular assist device

MAPK :

Mitogen-activated protein kinases

MCAD:

Medium-chain acyl-CoA dehydrogenase

miR:

Micro-RNA

MI:

Myocardial infarction

MLP:

Muscle LIM protein

MMP:

Matrix metalloproteinase

mTOR:

Molecular target of rapamycin

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NFAT :

Nuclear factor of activated T cells

NOS:

Nitric oxide synthase

NOX:

NADPH oxidase

PI3K :

Phosphoinositide-3-kinase

PKA:

Protein kinase A

PKC:

Protein kinase C

PPAR:

Peroxisome proliferator-activated receptor

RyR2:

Ryanodine receptor type 2

SAC:

Stretch-activated ion channel

SERCA :

Sarcoplasmic reticulum Ca2+ ATPase

SOC:

Store-operated Ca2+ channel

TAC:

Transaortic constriction

TGF-β:

Tissue growth factor beta

TIMP:

Tissue inhibitor of metalloproteinase

TNF-α:

Tumor necrosis factor alpha

TnI:

Troponin I

TnT:

Troponin T

TRP:

Transient receptor potential

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA

    Raymond C. Givens MD, PhD & P. Christian Schulze MD, PhD

  2. Center for Advanced Cardiac Care, Columbia University Medical Center, Division of Cardiology, 622 West 168th Street, PH 10, Room 203, New York, NY, 10032, USA

    P. Christian Schulze MD, PhD

  3. Geier Clinical Research Center, Center for Advanced Cardiac Care, Division of Cardiology, Columbia University Medical Center, 622 West 168th Street, PH 10, Room 203, New York, NY, 10032, USA

    P. Christian Schulze MD, PhD

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Correspondence to P. Christian Schulze MD, PhD .

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  1. Division of Cardiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Howard Eisen

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Givens, R.C., Schulze, P.C. (2017). Molecular Changes in Heart Failure. In: Eisen, H. (eds) Heart Failure. Springer, London. https://doi.org/10.1007/978-1-4471-4219-5_1

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