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- Title
The Effect of Tafamidis on Circulating Endothelial Progenitor Cells in Patients with Transthyretin Cardiac Amyloidosis.
- Authors
Itzhaki Ben Zadok, Osnat; Leshem-Lev, Dorit; Ben-Gal, Tuvia; Hamdan, Ashraf; Schamroth Pravda, Nili; Steinmetz, Tali; Kandinov, Irit; Ovadia, Ilit; Kornowski, Ran; Eisen, Alon
- Abstract
Aims: Endothelial microvascular dysfunction is a known mechanism of vascular pathology in cardiac amyloidosis (CA). Scientific evidence regarding the possible protective role of the amyloid transthyretin (ATTR) stabilizer, tafamidis, is lacking. Circulating endothelial progenitor cells (cEPCs) have an important role in the process of vascular repair. We aimed to examine the effect of tafamidis on cEPCs. Methods and Results: Study population included patients with ATTR-CA. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+) and by the formation of colony-forming units (CFUs) and production of VEGF. Tests were repeated at pre-specified time-points up to 12 months following the initiation of tafamidis. Included were 18 ATTR-CA patients at a median age of 77 (IQR 71, 85) years and male predominance (n = 15, 83%). Following the initiation of tafamidis and during 12 months of drug treatment, there was a gradual increase in the levels of CD34(+)/VEGFR-2(+) (0.43 to 2.42% (IQR 1.53, 2.91)%, p = 0.002) and CD133(+)/VEGFR-2(+) (0.49 to 1.64% (IQR 0.97, 2.90)%, p = 0.004). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with tafamidis (from 0.5 CFUs (IQR 0.0, 1.0) to 3.0 (IQR 1.3, 3.8) p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (from 0.12 (IQR 0.03, 0.16) to 0.30 (IQR 0.18, 0.33), p < 0.001). VEGF levels increased following treatment (from 54 (IQR 52, 72) to 107 (IQR 62, 129) pg/ml, p = 0.039). Conclusions: Tafamidis induced the activation of the cEPCs pathway, possibly promoting endothelial repair in ATTR-CA.
- Subjects
CARDIAC amyloidosis; PROGENITOR cells; VASCULAR endothelial growth factor receptors; ENDOTHELIAL cells; CARDIAC patients
- Publication
Cardiovascular Drugs & Therapy, 2022, Vol 36, Issue 3, p489
- ISSN
0920-3206
- Publication type
Article
- DOI
10.1007/s10557-021-07265-0