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Review
. 2010 Nov;74(11):2249-56.
doi: 10.1253/circj.cj-10-0904. Epub 2010 Oct 15.

Cyclophilin A: promising new target in cardiovascular therapy

Kimio Satoh  1 , Hiroaki Shimokawa, Bradford C Berk
Affiliations
Review

Cyclophilin A: promising new target in cardiovascular therapy

Kimio Satoh et al. Circ J. 2010 Nov.

Abstract

Cyclophilin A (CyPA) has been studied as a multifunctional protein that is upregulated in a variety of inflammatory conditions, such as rheumatoid arthritis, autoimmune disease, and cancer. CyPA has been classified as an immunophilin and has a variety of intracellular functions, including intracellular signaling, protein trafficking, and the regulation of other proteins activity. Besides its intracellular functions, CyPA is a secreted molecule that has a physiological and pathological role in cardiovascular diseases, making it a potential biomarker and mediator in cardiovascular diseases, such as vascular stenosis, atherosclerosis, and abdominal aortic aneurysms.

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Figures

Figure 1
Figure 1
ROS-induced secretion of cyclophilin A (CyPA) synergistically augments ROS production. ROS inducers, such as angiotensin II (AngII), mechanical stress, and environmental factors, promote CyPA secretion from vascular smooth muscle cells (VSMC). Secreted CyPA activates ERK1/2 and promotes reactive oxygen species (ROS) production, thus augmenting it.
Figure 2
Figure 2
Cyclophilin A (CyPA) is a novel growth factor that mediates growth of vascular smooth muscle cells (VSMC) under oxidative stress. Decreased blood flow increases the generation of reactive oxygen species (ROS), which induces secretion of CyPA from VSMC. Secreted CyPA VSMC proliferation, endothelial cell (EC) adhesion molecule expression, and inflammatory cell migration (CD45-positive cells), resulting in vascular remodeling.
Figure 3
Figure 3
Proposed mechanisms for angiotensin II (AngII)-induced reactive oxygen species (ROS) production, cyclophilin A (CyPA) secretion, metalloproteinase (MMP) activation, and abdominal aorta aneurysm (AAA) formation. Secreted extracellular CyPA activates ERK1/2, Akt, and JAK in an autocrine/paracrine manner, which promotes proliferation and migration of vascular smooth muscle cells (VSMCs), MMP activation, and inflammatory cell migration.
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