mTOR inhibition improves mitochondria function/biogenesis and delays cardiovascular aging in kidney transplant...

Area of Science:

• Nephrology
• Cardiology
• Immunology

Background:

• Cardiovascular disease (CVD) is a leading cause of mortality in kidney transplant recipients (KTRs).
• KTRs have a significantly higher risk of cardiovascular events compared to the general population.
• Strategies to mitigate CV risk, including mTOR inhibitors, are under investigation.

Purpose of the Study:

• To evaluate the impact of chronic mTOR inhibition on cardiovascular aging in KTRs.
• To investigate the molecular mechanisms underlying the potential cardioprotective effects of mTOR inhibitors.

Main Methods:

• Retrospective analysis of 210 KTRs with stable graft function.
• Comparison between KTRs on calcineurin inhibitor (CNI) and mycophenolic acid (Group A) versus CNI and mTOR inhibitor (Everolimus) (Group B).
• Assessment of serum biomarkers (Klotho, FGF-23), cardiac structure (left ventricular mass), peripheral blood mononuclear cell (PBMC) mitochondrial function, and inflammaging markers.

Main Results:

• mTOR inhibitor use was associated with increased serum Klotho and decreased FGF-23 levels.
• Significant reduction in left ventricular mass observed in the mTOR inhibitor group.
• Improved mitochondrial function, enhanced oxidative phosphorylation, and increased antioxidant capacity in PBMCs of KTRs on mTOR inhibitors.
• Reduced levels of inflammaging markers (pentraxin-3, p21ink expression) in the mTOR inhibitor group.

Conclusions:

• Chronic mTOR inhibition in immunosuppressive protocols for KTRs prevents cardiovascular aging.
• mTOR inhibitors positively influence key molecular pathways related to aging and cardiovascular health in KTRs.
• This study provides evidence for the cardioprotective potential of mTOR inhibitors in kidney transplant recipients.