TY - JOUR
T1 - mTOR inhibition improves mitochondria function/biogenesis and delays cardiovascular aging in kidney transplant recipients with chronic graft dysfunction
AU - Infante, Barbara
AU - Bellanti, Francesco
AU - Correale, Michele
AU - Pontrelli, Paola
AU - Franzin, Rossana
AU - Leo, Serena
AU - Calvaruso, Martina
AU - Mercuri, Silvia
AU - Netti, Giuseppe Stefano
AU - Ranieri, Elena
AU - Brunetti, Natale Daniele
AU - Grandaliano, Giuseppe
AU - Gesualdo, Loreto
AU - Serviddio, Gaetano
AU - Castellano, Giuseppe
AU - Stallone, Giovanni
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - cardiovascular aging
KW - kidney disease
KW - kidney transplantation
KW - mTOR inhibitor
KW - mitochondria
KW - cardiovascular aging
KW - kidney disease
KW - kidney transplantation
KW - mTOR inhibitor
KW - mitochondria
UR - http://hdl.handle.net/10807/181183
U2 - 10.18632/aging.202863
DO - 10.18632/aging.202863
M3 - Article
SN - 1945-4589
VL - 13
SP - 8026
EP - 8039
JO - Aging
JF - Aging
ER -