Annexin 1 and melanocortin peptide therapy for protection against ischaemic-reperfusion damage in the heart.
ScientificWorldJournal
; 6: 1008-23, 2006 Aug 25.
Article
em En
| MEDLINE
| ID: mdl-16937007
ABSTRACT
Cardiovascular disease is a major cause of mortality within the western world affecting 2.7 million British people. This review highlights the beneficial effects of naturally occurring hormones and their peptides, in myocardial ischaemic-injury (MI) models, a disease pathology in which cytokines and neutrophils play a causal role. Here we discuss two distinct classes of endogenous peptides the steroid inducible annexin 1 and the melanocortin peptides. Annexin 1 and the melanocortins counteract the most important part of the host inflammatory response, namely, the process of leukocyte extravasation, as well as release of proinflammatory mediators. Their biological effects are mediated via the seven transmembrane G-protein-coupled receptors, the fMLP receptor family (or FPR), and the melanocortin receptors, respectively. Pharmacological analysis has demonstrated that the first 24 amino acids of the N-terminus (termed Ac2-26) are the most active region. Both exogenous annexin 1 and its peptides demonstrate cardioprotectiveness and continuing work is required to understand this annexin 1/FPR relationship fully. The melanocortin peptides are derived from a precursor molecule called the POMC protein. These peptides display potent anti-inflammatory effects in human and animal models of disease. In MI, the MC3R has been demonstrated to play an important role in mediating the protective effects of these peptides. The potential anti-inflammatory role for endogenous peptides in cardiac disease is in its infancy. The inhibition of cell migration and release of cytokines and other soluble mediators appears to play an important role in affording protection in ischaemic injury and thus may lead to potential therapeutic targets.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Pró-Opiomelanocortina
/
Traumatismo por Reperfusão Miocárdica
/
Anexina A1
Limite:
Animals
/
Humans
Idioma:
En
Revista:
ScientificWorldJournal
Assunto da revista:
MEDICINA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Reino Unido