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RhoA/Rho-Associated Kinase as Marker of Cardiovascular Health

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Biomarkers in Cardiovascular Disease

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Abstract

Rho-associated coiled-coil kinase (ROCK) is a widely expressed intracellular signaling molecule. ROCK is the best-described downstream regulator of Rho and regulates numerous cellular functions such as division, migration, growth, and death. ROCK activity has been implicated in the development of various forms of cardiovascular disease including stroke, coronary artery disease, hypertension, and several others. While much effort has been devoted to the study of ROCK inhibitors and their potential role in the treatment of cardiovascular disease, a growing body of evidence suggests that HMG-CoA reductase inhibitors (statins) indirectly inhibit ROCK by preventing the necessary preceding step of Rho tethering to the plasma membrane. In this way, statins are believed to exert beneficial cholesterol-independent or “pleiotropic” effects. In the following chapter, we will discuss the molecular structure of ROCK, the regulation of the Rho/ROCK pathway, the role of Rho/ROCK in numerous forms of cardiovascular disease, and the available evidence implicating ROCK as a pharmaceutical target.

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Abbreviations

ACS:

Acute coronary syndrome

AGE:

Advanced glycation end products

ApoE:

Apolipoprotein-E

BMI:

Body mass index

CAD:

Coronary artery disease

DNA:

Deoxyribonucleic acid

EKG:

Electrocardiogram

eNOS:

Endothelial nitric oxide synthase

ERM:

Ezrin-radixin-moesin

FMD:

Flow-mediated dilatation

FPP:

Farnesyl pyrophosphate

GGPP:

Geranylgeranyl pyrophosphate

GTP:

Guanosine-5′-triphosphate

HMG-CoA:

3-hydroxy-3-methylglutaryl-coenzyme A

hsCRP:

High-sensitivity C-reactive protein

ICAM:

Intercellular adhesion molecule

IF:

Intermediate filaments

IFN:

Interferon

IL:

Interleukin

IRS:

Insulin receptor substrate

JNK:

c-Jun NH(2)-terminal kinase

KD:

Knockdown

LDL:

Low-density lipoprotein

LIMK:

(Lin11, Isl-1, and Mec-3) domain kinase

L-NAME:

N ω-Nitro-l-arginine methyl ester

LPA:

Lysophosphatidic acid

MBS:

Myosin-binding subunit

MCA:

Middle cerebral artery

MCP:

Monocyte chemoattractant protein

MLC:

Myosin light chain

MLCP:

Myosin light chain phosphatase

NF-κB:

Nuclear factor κB

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NSTEMI:

Non-ST segment elevation myocardial infarction

NT-pro-BNP:

N-terminal prohormone of brain natriuretic peptide

PAD:

Peripheral arterial disease

PAH:

Pulmonary arterial hypertension

PAI:

Plasminogen activator inhibitor

PCI:

Percutaneous coronary intervention

PDGF:

Platelet-derived growth factor

PH:

Pleckstrin homology

PIP:

Phosphatidylinositol (3,4,5)-trisphosphate

PIP5K:

Phosphatidylinositol 4-phosphate 5-kinase

PKC:

Protein kinase C

PTEN:

Phosphatase and tensin homologue

RBD:

Rho-binding domain

ROCK:

Rho-associated coiled-coil kinase

ROS:

Reactive oxygen species

S1P:

Sphingosine-1-phosphate

SNP:

Single-nucleotide polymorphism

STEMI:

ST segment elevation myocardial infarction

TCR:

T-cell receptor

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

VEGF:

Vascular endothelial growth factor

VSMCs:

Vascular smooth muscle cells

WT:

Wild type

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Authors and Affiliations

  1. University of Chicago Medicine, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA

    Corey E. Tabit

  2. Stroke Biological Recovery Laboratory, Spaulding Rehabilitation Hospital, 300 First Avenue, Charlestown, MA, 02135, USA

    Qing Mei Wang

  3. Department of Pediatric Dentistry, Tufts University School of Dental Medicine, 1 Kneeland Street, Boston, MA, 02111, USA

    Robert Y. L. Zee

  4. Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, 900 Commonwealth East, Boston, MA, 02215, USA

    Robert Y. L. Zee

  5. Section of Cardiology, University of Chicago Medicine, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA

    James K. Liao

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  1. Corey E. Tabit
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  2. Qing Mei Wang
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  4. James K. Liao
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Correspondence to James K. Liao .

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  1. Department of Biomedical Science, Faculty of Science & Technology , University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Department of Nutrition and Dietetics, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom

    Victor R. Preedy

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Tabit, C.E., Wang, Q.M., Zee, R.Y.L., Liao, J.K. (2016). RhoA/Rho-Associated Kinase as Marker of Cardiovascular Health. In: Patel, V., Preedy, V. (eds) Biomarkers in Cardiovascular Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7678-4_17

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