mTOR inhibition improves mitochondria function/biogenesis and delays cardiovascular aging in kidney transplant recipients with chronic graft dysfunction

Giuseppe Grandaliano, Barbara Infante, Francesco Bellanti, Michele Correale, Paola Pontrelli, Rossana Franzin, Serena Leo, Martina Calvaruso, Silvia Mercuri, Giuseppe Stefano Netti, Elena Ranieri, Natale Daniele Brunetti, Loreto Gesualdo, Gaetano Serviddio, Giuseppe Castellano, Giovanni Stallone

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

Abstract

CVD remains the major cause of mortality with graft functioning in Kidney transplant recipients (KTRs), with an estimated risk of CV events about 50-fold higher than in the general population. Many strategies have been considered to reduce the CV risk such as the use of mTOR inhibitors. We evaluate whether chronic mTOR inhibition might influence CV aging in KTRs studying the molecular mechanisms involved in this effect. We retrospectively analyzed 210 KTRs with stable graft function on therapy with CNI and mycophenolic acid (Group A, 105 pts.), or with CNI and mTORi (Everolimus, Group B, 105 pts.). The presence of mTOR inhibitor in immunosuppressive therapy was associated to increase serum levels of Klotho with concomitant reduction in FGF-23, with a significant decrease in left ventricular mass. In addition, KTRs with mTORi improved mitochondrial function/biogenesis in PBMC with more efficient oxidative phosphorylation, antioxidant capacity and glutathione peroxidase activity. Finally, group B KTRs presented reduced levels of inflammaging markers such as reduced serum pentraxin-3 and p21ink expression in PBMC. In conclusion, we demonstrated that mTOR inhibition in immunosuppressive protocols prevents the occurrence and signs of CV aging in KTRs.
Lingua originaleEnglish
pagine (da-a)8026-8039
Numero di pagine14
RivistaAging
Volume13
DOI
Stato di pubblicazionePubblicato - 2021

Keywords

  • cardiovascular aging
  • kidney disease
  • mTOR inhibitor
  • mitochondria
  • kidney transplantation

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