Cyclophilin A Functions in Inflammation and Vascular Pathophysiology

Cyclophilin A (CypA) is a highly conserved peptidyl-prolyl cis-trans isomerase abundantly expressed in most cell types. Beyond its intracellular role in protein folding and trafficking, CypA is secreted by endothelial cells, smooth muscle cells and leukocytes in response to oxidative stress, hyperglycaemia and inflammatory stimuli. In the extracellular milieu it binds to the transmembrane glycoprotein CD147, activating downstream kinases (including ERK1/2 and NF-κB) to promote cytokine release, leukocyte chemotaxis and matrix metalloproteinase expression. These actions drive endothelial dysfunction, vascular smooth muscle proliferation and degradation of the extracellular matrix, key events in atherogenesis, plaque instability and aneurysm formation. Elevated circulating levels of CypA have been observed in metabolic and cardiovascular disorders, where they correlate with disease severity. Modulation of CypA activity—either by small-molecule inhibitors or by blocking its interaction with CD147—has shown efficacy in preclinical models of vascular inflammation, myocardial remodelling and fibrotic sequelae, highlighting its potential as a therapeutic target to limit vascular injury and accelerate repair.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Cyclophilin A Functions in Inflammation and Vascular Pathophysiology publication trend

The graph below shows the total number of articles in cyclophilin a functions in inflammation and vascular pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

Cyclophilin A (CypA): A ubiquitously expressed peptidyl-prolyl cis-trans isomerase that facilitates protein folding and, when secreted, acts as a pro-inflammatory signalling ligand.

Peptidyl-prolyl cis-trans isomerase (PPIase): An enzyme that catalyses the interconversion of peptide bonds at proline residues, influencing protein conformation and activity.

CD147 (EMMPRIN): A cell‐surface glycoprotein that binds extracellular CypA, triggering intracellular signalling cascades and induction of matrix metalloproteinases.

Matrix metalloproteinases (MMPs): A family of zinc-dependent enzymes that degrade extracellular matrix proteins, pivotal in tissue remodelling and vascular lesion progression.

Reactive oxygen species (ROS): Highly reactive oxygen-derived molecules that act as signalling intermediates in inflammation and vascular injury.

References

1. Extracellular Matrix Metalloproteinase Inducer EMMPRIN (CD147) in Cardiovascular Disease. International Journal of Molecular Sciences (2018).
2. Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity DIRECT BINDING BETWEEN CyPA AND THE ECTODOMAIN OF CD147*. Journal of Biological Chemistry (2011).
3. Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease. Cardiovascular Diabetology (2014).
4. The Novel Extracellular Cyclophilin A (CyPA) - Inhibitor MM284 Reduces Myocardial Inflammation and Remodeling in a Mouse Model of Troponin I -Induced Myocarditis. PLOS ONE (2015).
5. Cyclophilin A (CypA) Interacts with NF-κB Subunit, p65/RelA, and Contributes to NF-κB Activation Signaling. PLOS ONE (2014).