Sirolimus affects cardiomyocytes to reduce left ventricular mass in heart transplant recipients
Open Access
- 30 May 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in European Heart Journal
- Vol. 29 (22), 2742-2750
- https://doi.org/10.1093/eurheartj/ehn407
Abstract
The cellular mechanisms underlying cardiac hypertrophy may result from changes in cardiac myocyte growth and differentiation. We tested whether sirolimus, an immunosuppressive agent that inhibits mTOR, a protein that regulates cell division and differentiation, might modify cardiac hypertrophy after cardiac transplantation. Fifty-eight cardiac transplant recipients were withdrawn from treatment with calcineurin inhibitors (CNIs) and treated with sirolimus. Eighty-three control subjects were maintained on CNIs. After 12 months, left ventricular (LV) mass decreased from 196.15 ± 48.28 to 182.21 ± 43.56 g (P = 0.05) and LV mass index from 99.25 ± 20.08 to 93.82 ± 20.22 g/m2 (P = 0.031) in sirolimus-treated subjects but did not change in controls. The left atrial volume index of sirolimus-treated subjects decreased from 52.44 ± 17.22 to 48.40 ± 15.14 cc/m2 (P = 0.008) and increased from 52.07 ± 19.45 to 57.03 ± 19.93 cc/m2 (P = 0.0012) in controls. The difference between the groups was independent of blood pressure. The number of cells in myocardial biopsies positive for p27Kip1, a protein induced by mTOR inhibition, increased in sirolimus-treated subjects (P = 0.0005) and did not change in controls (P = 0.54) suggesting sirolimus acted directly on myocardium. Sirolimus may inhibit adverse ventricular remodelling resulting in cardiac hypertrophy and have potential in the treatment of conditions in which severe hypertrophy compromises cardiac function.Keywords
This publication has 51 references indexed in Scilit:
- Left Ventricular Hypertrophy, Subclinical Atherosclerosis, and InflammationHypertension, 2007
- Prevalence and prognostic implications of electrocardiographic left ventricular hypertrophy in heart failure: evidence from the CHARM programmeHeart, 2007
- Effects of Conversion from Cyclosporine to Tacrolimus on Left Ventricular Structure in Cardiac Allograft RecipientsThe Journal of Heart and Lung Transplantation, 2005
- The Transition From Hypertrophy to FailureCirculation, 2005
- Transforming growth factor β and diastolic left ventricular dysfunction after heart transplantation: echocardiographic and histologic evidenceThe Journal of Heart and Lung Transplantation, 2003
- Rapamycin Attenuates Load-Induced Cardiac Hypertrophy in MiceCirculation, 2003
- Mechanism of action of the immunosuppressant rapamycinLife Sciences, 1995
- Comparative accuracy of Doppler echocardiographic methods for clinical stroke volume determinationAmerican Heart Journal, 1990
- Prognostic Implications of Echocardiographically Determined Left Ventricular Mass in the Framingham Heart StudyThe New England Journal of Medicine, 1990
- A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography.Circulation, 1981