RESUMO
The binding of advanced glycation endproducts (AGEs) to their receptors is known to cause changes in cell function during normal ageing and is implicated in the pathogenesis of cardiovascular disease. In this study, expression of the AGE-receptor 3 (AGE-R3) and the receptor for AGEs (RAGE) was compared on the mRNA and protein level in the ageing human heart. Western blot and RT-PCR analysis of the AGE receptors from the cardiac auricles in senescent and adult patients was performed and compared with young controls. Whereas the expressions of AGE-R3 as well as RAGE protein were significantly upregulated in the senescent population, only the upregulation of RAGE is associated with reduced heart function. Therefore, our results support a pathophysiological function for RAGE in the ageing human heart.
Assuntos
Envelhecimento/fisiologia , Doença das Coronárias/metabolismo , Produtos Finais de Glicação Avançada/análise , Miocárdio/química , Receptores Imunológicos/análise , Adulto , Idoso , Western Blotting/métodos , Débito Cardíaco , Pré-Escolar , Doença das Coronárias/fisiopatologia , Produtos Finais de Glicação Avançada/genética , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/análise , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Advanced glycation end products (AGEs) are formed by the reaction of sugars and NH2 groups of lysine and arginine residues and have been shown to accumulate in tissues, including the heart, with normal ageing. The interaction of AGEs with their receptors is known to cause changes in cell function, leading, for example, to the production of pro-inflammatory cytokines and free radicals. OBJECTIVE: This study investigated the gene expression of the five known AGE receptors: AGE-R1, AGE-R2, AGE-R3, the scavenger receptor II, and the receptor for AGEs (RAGE) in human heart tissue. METHODS: Tissue samples were taken from the right cardiac auricles from three patient groups: children (2.4 +/- 1.1 years), adults (45.3 +/- 0.8 years) and elderly subjects (76.4 +/- 0.4 years). Analysis of gene expression of the five AGE receptors was performed using the reverse transcription-polymerase chain reaction (RT-PCR) and 18S mRNA levels as loading controls. RESULTS: Our results show an age-dependent upregulation of the genes for AGE-R3 and the scavenger receptor II, but a downregulation for RAGE and no significant differences for AGE-R1 and AGE-R2. CONCLUSION: This study supports a pathophysiological function for AGE receptors such as AGE-R3 and RAGE in the ageing heart.