TAVR as Anti-Inflammatory? An effect few imagined

We never saw it coming, such a pleiotropic effect: who would have though a mechanical device could have such a systemic anti-inflammatory effect? Transcatheter aortic valve replacement (TAVR) does in fact have it. 

The shear stress aortic stenosis produces activates multiple inflammatory responses mediated by monocytes. This study identified the most important mechanoreceptor, involved in the inflammatory cascade called Piezo-1. This receptor is a potentially druggable target, and although we have not yet been able to block it, we can prevent it from increasing inflammation by lowering shear stress with TAVR. 

The chance of aortic stenosis accelerating or provoking inflammation per se was unknown until now. 

TAVR has given us the unique opportunity to compare the activation status of monocytes under high shear stress (before TAVR) and under low shear stress (after TAVR).

The activation status of monocytes was determined using MAN-1 antibodies, which are specific for the activated B2 integrin Mac-1.

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Activated monocytes adhere to stimulated endothelial cells, phagocytic activity, oxidized low density lipoproteins and cytokine expression. 

Different assays were carried out to collect this information before and after TAVR.

After TAVR, shear stress was reduced, with the resulting reduction of Mac-1 activity, cell adhesion, low density lipoprotein oxidation and inflammatory marker expression in the circulating monocytes. 

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Researchers also observed in the lab, under strictly controlled conditions, that shear stress-dependent calcium influx and monocyte adhesion are mediated by the mechanosensitive ion channel Piezo-1. 

Expression of this receptor depends on shear stress and it clearly drops after TAVR.

Conclusion

This study shows that shear stress produced by diseases such as severe aortic stenosis activates multiple monocyte functions mediated by the mechanosensitive Piezo-1. It also shows the anti-inflammatory effect of TAVR and therefore its new and unknow therapeutic benefit. 

Original Title: Transcatheter Aortic Valve Implantation Represents an Anti-Inflammatory Therapy Via Reduction of Shear Stress–Induced, Piezo-1–Mediated Monocyte Activation.

Reference: Sara Baratchi et al. Circulation. 2020;142:1092–1105.  DOI: 10.1161/CIRCULATIONAHA.120.045536.

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