Myocardial and lymphocytic expression of eNOS and nNOS before and after heart transplantation: relationship to clinical status

Aims: The present study investigates the expression and clinical relevance of the constitutive NO synthases in heart and peripheral blood mononuclear cells (PBMCs) obtained from heart failure patients.

Main methods: mRNA and protein levels (qRT-PCR and immunoblot) of eNOS and nNOS were determined in: i) Left ventricle (LV, n=4) and PBMCs (n=10) from healthy donors; ii) LV, right ventricle (RV) and PBMCs of heart failure (HF) patients (n=32); and iii) biopsies and PBMCs of the HF patients after cardiac transplant (n=15).

Key findings: Expression of constitutive NOS isoforms in heart exhibits wide variability in HF patients, but this variability was not related to aetiology, disease severity, concomitant pathologies or drug regimes. A significantly increased eNOS expression was found in LV from HF patients without vs. with pulmonary hypertension. Overall, higher eNOS expression in this chamber was associated with lower pulmonary arterial pressure. Furthermore, a higher eNOS expression in HF is associated with smaller LV diameter, whereas, a higher post-transplant eNOS expression is related to greater cardiac distensibility. In the RV, nNOS increased after transplant. The positive correlation found between the nNOS expression in the LV of HF patients and the cardiac index suggests a role for this isoform in facilitating cardiac work. A decreased expression of eNOS was observed in PBMCs from HF patients vs. healthy donors, which recovers after transplant.

Significance: A selective up-regulation of the cardiac expression of each NOS isoform in the failing heart, which is not mirrored by PBMCs, is related to an improved health status.