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Pathways to Myocardial Hypertrophy

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Introduction to Translational Cardiovascular Research

Abstract

Pathological cardiac hypertrophy occurs as a consequence of adaptive responses to pressure or volume overload, mutations in sarcomeric (or other) proteins, or loss of contractile mass from prior infarction. While initially compensatory, over time when the heart can no longer meet with the increased metabolic demands of the mechanical work load imposed on the heart, dilation and heart failure ensue. Several signaling pathways are critically important in mediating myocardial hypertrophy, including the G-protein coupled receptor, the calcineurin/NFAT, MAPK, and the PI3K/AKT/mTOR signaling pathways. Importantly, these signaling pathways also control molecular processes, such as cell proliferation, differentiation, survival, migration and other functions of the cell. In addition, the heart is comprised of several cell lineages make up the heart, including cardiomyocytes, fibroblasts, endothelial cells, and vascular smooth muscle cells, each integrally involved in modulating the signaling events that promote the hypertrophic growth of the heart. In this chapter we discuss these molecular pathways and how the aberrant regulation of initially compensatory responses becomes pathological. We will also discuss potential therapeutic targets for hypertrophic cardiomyopathy and heart failure, with a focus on treating this devastating worldwide disease.

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Abbreviations

ACEIs:

Angiotensin-converting-enzyme inhibitors

AngII:

Angiotensin II

ATP:

Adenosine triphosphate

ATR:

Angiotensin receptor

b-FGF:

basic fibroblast growth factor

C:

Adenylyl cyclase

CaMKII:

Ca2+/calmodulin-dependent protein kinase II

cAMP:

Cyclic adenosine 3′ 5′ monophosphate

CICR:

Calcium-induced Calcium Release

CMs:

Cardiomyocytes

CsA:

Cyclosporine A

ECM:

Extracellular matrix

ECs:

Endothelial cells

ERK:

Extracellular regulated kinase

G protein:

Guanosine triphosphate binding protein

G-protein:

GTP-binding protein

GSK3β:

Glycogen synthase kinase 3-β

HCM:

Hypertrophic Cardiomyopathy

HDACs:

Histone deacetylases

HF:

Heart Failure

IGF-1:

Insulin-like growth factor-1

JNK:

Jun N-terminal kinase

LTCC:

Long-type Calcium Channel

LV:

Left ventricular

MAPK:

Mitogen activated protein kinase

MI:

Myocardial infarction

mTOR:

Mammalian target of Rapamycin

Na+ :

Sodium irons

NFAT:

Nuclear factor for activation of T cells

NO:

Nitric Oxide

PI3K:

xPhosphatidylinositol 3′ kinase

PKC:

Protein kinase C

PLN:

Phospholamban

PTEN:

Phosphatase and tensin homolog deleted on chromosome ten

RAS:

Renin–angiotensin system

RyR:

Ryanodone receptor

SR:

Sarcoplasmic reticulum

STAT:

Signal transducer and activators of transcription

TGFβ:

Transforming growth factor-β

T-tubule:

Transverse tubule2

VEGF:

Vascular endothelial growth factor

VSMCs:

Vascular smooth muscle cells

α-AR:

Alpha adrenergic receptor

β1AR:

Beta 1adrenergic receptor

βAR:

Beta adrenergic receptor

βMHC:

Beta myosin heavy chain

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Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

    Maria Irene Kontaridis PhD

  2. Division of Cardiology, Department of Medicine, Center for Life Sciences, Beth Israel Deaconess Medical Center, Room 908, 3 Blackfan Circle, Boston, MA, USA

    Maria Irene Kontaridis PhD, Eleni V. Geladari MD & Charalampia V. Geladari MD

  3. Department of Internal Medicine, Evangelismos State General Hospital, Athens, Greece

    Eleni V. Geladari MD

  4. 4th Department of Internal Medicine, Evangelismos State General Hospital, Athens, Greece

    Charalampia V. Geladari MD

Authors
  1. Maria Irene Kontaridis PhD
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  2. Eleni V. Geladari MD
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  3. Charalampia V. Geladari MD
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Corresponding author

Correspondence to Maria Irene Kontaridis PhD .

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Editors and Affiliations

  1. Academy of Athens, Biomedical Research Foundation, Athens, Greece

    Dennis V. Cokkinos

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Kontaridis, M.I., Geladari, E.V., Geladari, C.V. (2015). Pathways to Myocardial Hypertrophy. In: Cokkinos, D. (eds) Introduction to Translational Cardiovascular Research. Springer, Cham. https://doi.org/10.1007/978-3-319-08798-6_10

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  • DOI: https://doi.org/10.1007/978-3-319-08798-6_10

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