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Cyclophilin A: Novel Biomarker for Oxidative Stress and Cardiovascular Diseases

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General Methods in Biomarker Research and their Applications

Abstract

Intracellular redox status is closely regulated by the balance between oxidant and antioxidant systems, and their imbalance can cause oxidative or reductive stress, leading to cellular damage and dysregulation. Excessive reactive oxygen species (ROS) deteriorates vascular functions and promotes vascular diseases through multiple pathways. Recently, cyclophilin A (CyPA) has been shown to be secreted from vascular smooth muscle cells (VSMC) and to augment the destructive effects of ROS, linking it to the development of many cardiovascular diseases. In the secretion of CyPA, Rho-kinase plays an important role to organize vicious cycle for augmentation of ROS. The important role of Rho-kinase has been established in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, it is important to understand Rho-kinase signaling and the role of downstream effectors such as CyPA in the vascular system in order to develop new therapeutic strategies for cardiovascular diseases. Here, we reported that plasma CyPA levels are increased in patients with coronary artery disease (CAD). Plasma CyPA levels were significantly higher in patients with significant coronary stenosis compared to those without it. A positive correlation was noted between plasma CyPA levels and significant coronary stenosis. The average number of stenotic coronary arteries and the need for coronary intervention were significantly increased in the quartiles of higher CyPA levels. Interestingly, plasma levels of CyPA increased according to the number of atherosclerotic risk factors, all of which induce oxidative stress. Furthermore, plasma levels of CyPA significantly reduced after medical treatment of risk factors. In this chapter, we will discuss the roles of VSMC-derived CyPA in promoting vascular diseases, with particular emphasis on the role of CyPA as a novel biomarker for CAD. Additionally, we will mention the beneficial effects of fasudil, a selective Rho-kinase inhibitor, for the treatment of cardiovascular diseases.

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Abbreviations

AngII:

Angiotensin II

CAD:

Coronary Artery Disease

Cdc42:

Cell Division Control Protein 42

cGMP:

Cyclic Guanosine Monophosphate

CyPA:

Cyclophilin A

CyPB:

Cyclophilin B

CyPC:

Cyclophilin C

CyPD:

Cyclophilin D

EC:

Endothelial Cells

EDHF:

Endothelium-Derived Hyperpolarizing Factors

eNOS:

Endothelial NO Synthase

ERK:

Extracellular Signal-Regulated Kinase

H2O2 :

Hydrogen Peroxide

JAK:

Janus Protein Tyrosine Kinase

NADPH:

Nicotinamide Adenine Dinucleotide Phosphate

NO:

Nitric Oxide

Nox:

NADPH Oxidases

O2 − :

Superoxide Anions

•OH:

Hydroxyl Radical

ONOO− :

Peroxynitrite

PAH:

Pulmonary Arterial Hypertension

PH:

Pulmonary Hypertension

PPIase:

Peptidyl-Prolyl isomerase

ROCK:

Rho/Rho-Kinase

ROS:

Reactive Oxygen Species

SMA:

Smooth Muscle Actin

SOD:

Superoxide Dismutase

SOXF:

Secreted Oxidative Stress-Induced Factors

TNFα:

Tumor Necrosis Factor-α

VCAM-1:

Vascular Cell Adhesion Molecule-1

VSMC:

Vascular Smooth Muscle Cells

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Japan

    Kimio Satoh & Hiroaki Shimokawa

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  1. Kimio Satoh
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  2. Hiroaki Shimokawa
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Correspondence to Hiroaki Shimokawa .

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

    Victor R. Preedy

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

    Vinood B. Patel

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Satoh, K., Shimokawa, H. (2015). Cyclophilin A: Novel Biomarker for Oxidative Stress and Cardiovascular Diseases. In: Preedy, V., Patel, V. (eds) General Methods in Biomarker Research and their Applications. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7696-8_40

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