ACE2 and ACE in acute and chronic rejection after human heart transplantation.

OBJECTIVES

The authors sought to evaluate cardiac activity of angiotensin-converting enzyme (ACE) and ACE2 after heart transplantation (HT) and its relation with acute rejection (AR) and chronic allograft vasculopathy (CAV).

BACKGROUND

The renin-angiotensin system is altered in heart failure and HT. However, ACE and ACE2 activities in post-HT acute and chronic rejection have not been previously studied.

METHODS

HT patients (n = 45) were included when appropriate serial endomyocardial biopsies (EMB) and coronary angiography were available for analysis. In 21 patients, three post-HT time points were selected for CAV study in EMB tissue: basal (0-3 wks), second (2-3 months) and third (4-5 months). At 10 years post-HT, CAV was evaluated by coronary angiography (CA) and patients were grouped by degree of CAV: 0-1, non-CAV (n = 15) and 2-3, CAV (n = 6). For the AR study, 28 HT patients with evidence of one EMB rejection at grade 3 and two EMB grade 1A and/or 1B rejections were selected.

RESULTS

Post-HT, ACE2 activity was increased in the CAV group, compared to non-CAV. Patients with AR showed increased ACE, but not ACE2, activity.

CONCLUSIONS

Our results suggest that early post-HT cardiac ACE2 activity may have an important role in CAV development. In contrast, ACE activity was increased in AR. The renin-angiotensin system seems to be altered after HT and strategies to balance the system may be useful.