Evaluation of transcriptional levels of the natriuretic peptides, endothelin-1, adrenomedullin, their receptors and long non-coding RNAs in rat cardiac tissue as cardiovascular biomarkers of aging

Chronological age is considered one of the major risk factors for cardiovascular disease and mortality. The studyaimed to evaluate the transcriptional levels of the natriuretic peptides (NP), endothelin (ET)-1, adrenomedullin(ADM), their receptors and long non-coding (Lnc) RNA MIAT, MALAT-1, CARMEN and XIST in rat cardiac tissueas cardiovascular biomarkers of aging. Three groups of male Wistar rats were studied: A (n = 6; young), B(n = 13; adult), C (n = 10; old). Total RNA was extracted from left ventricle and analyzed by Real-Time PCR.Echocardiographic and histological analyses were performed. A significant increase of Atrial NP (ANP) and BrainNP (BNP) mRNA was observed in C while C-type NP (CNP) remained in a steady-state in B and C; ET-1 mRNAincreased significantly as a function of age. Any difference was observed for NP receptors. ETeA expression wasstatistically lower in B than A while ETeB were similar in all the three groups. The ADM showed an oppositetrend to that of the other peptides decreasing significantly as a function of age and presenting a counter-reg-ulation of calcitonin receptor-like receptor (CLR) and receptor activity modifying protein (RAMP)-2. LncRNAtranscripts decreased significantly as a function of age except for XIST. ADM and LncRNA trend suggest that theanimals are subjected to "successful aging" as also confirmed by histological analysis. Applying a multivariatelogistic regression analysis, only LnANP (p = 0.003) and LnADM (p = 0.023) resulted significantly associatedwith aging identifying them, for the first time, as independent markers of aging. The study underlining theimportance of a multi-label biomolecular approach in the evaluation of aging.