Adrenomedullin and intermedin gene transcription is increased in leukocytes of patients with chronic heart failure at different stages of the disease

Abstract

Adrenomedullin (ADM) is a vasodilatory peptide expressed in many tissues. Its levels are elevated in various diseases including chronic heart failure (CHF) and it has been suggested that the up-regulation of ADM in cardiac disease represents a protective mechanism. Similarly, intermedin (IMD), a novel member of the calcitonin/calcitonin gene-related peptide family, is considered a potential endogenous protector of the heart. Previous studies demonstrated that in CHF patients, elevated plasma concentrations of ADM and IMD reflect the patient's disease severity and prognosis, while the behavior of mRNA expression is not known. The aim of this study was to evaluate ADM/IDM transcriptomic profiling in human leukocytes of CHF patients as a function of clinical severity, assessing possible changes with respect to healthy subjects (C). mRNA expression was evaluated by Real-Time PCR and total RNA was extracted from leukocytes of C (n=8) and from CHF patients (NYHA I-II n=10; NYHA III-IV n=14) with PAXgene Blood RNA Kit. Significantly higher levels of ADM and IMD mRNA were found in CHF as a function of clinical severity (ADM: C=0.03 ± 0.013, NYHA I-II=0.11 ± 0.084, NYHA III-IV=11.46 ± 4.72, p=0.037 C vs NYHA III-IV, p=0.028 NYHA I-II vs NYHA III-IV; IMD: C=0.158 ± 0.041, NYHA I-II=0.93 ± 0.40, NYHA III-IV=2.6 ± 0.67, p=0.014 C vs NYHA III-IV, p=0.014 NYHA I-II vs NYHA III-IV). This study highlights, for the first time, the possibility of evaluating ADM and IMD mRNA expression in human whole blood samples by Real-Time PCR study providing further relevant information and providing a more complete interpretation of the pathophysiology of the disease.

Keywords: Adrenomedullin; Heart failure; Human leukocytes; Intermedin; Leukocyte mRNA expression; Real-Time PCR.