Adrenomedullin ameliorates the development of atherosclerosis in apoE-/- mice.

Abstract

Adrenomedullin (ADM) is a multifunctional peptide regulating cardiovascular homeostasis. We studied the role of ADM in the pathogenesis of atherosclerosis by investigating changes in ADM and its receptors - calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) - in aorta of apoE-/- mice and the effect of exogenous ADM administration. ApoE-/- mice were fed an atherogenic diet for 4 weeks, and apoE-/-+ADM mice were additionally given subcutaneous injections of ADM, 300ng/kg/h, for 4 weeks. ApoE-/- mice fed an atherogenic diet showed hyperlipidemia, a large plaque area and increased vessel wall thickness. The mRNA expression and protein level of ADM/ADM receptors were increased in the aorta, compared with C57BL/6J mice. The elevated mRNA level of CRLR and RAMPs correlated positively with ADM mRNA level. Radioimmunoassay revealed a higher plasma and aorta ADM content, by 61.6% and 285% (both P<0.01), respectively, in apoE-/- mice than that in C57BL/6J mice. Exogenous ADM significantly ameliorated dyslipidemia in apoE-/- mice. ADM-treated mice showed fewer aortic plaques, decreased plaque area, by 76% (P<0.01), and reduced ratio of plaque area to luminal area, by 65% (P<0.01), and ultrasonography revealed significantly reduced intima-media thickness of the ascending branch and abdominal aorta. The results suggest that atherosclerotic apoE-/- mice fed an atherogenic diet showed upregulated endogenous ADM and its receptors, and exogenous ADM treatment ameliorated the dyslipidemia and vascular atherosclerotic lesions. ADM/ADM receptors might be an important protective system against atherosclerosis and could become a new target of prevention and therapy for atherosclerosis.

• Authors: Chun Shui Pan, Jing Zhang, Fang Yu, Xu Teng, Chang Qi Cao, Wei Wu, Chao Shu Tang, Yong Fen Qi
• Journal: Peptides (Peptides) Vol. 31 Issue 6 Pg. 1150-8 (Jun 2010) ISSN: 1873-5169 [Electronic] United States
• PMID: 20332006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Apolipoproteins E
• Calcitonin Receptor-Like Protein
• Calcrl protein, mouse
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• RNA, Messenger
• Receptor Activity-Modifying Proteins
• Receptors, Adrenomedullin
• Receptors, Calcitonin
• Receptors, Peptide
• Adrenomedullin

Topics

• Adrenomedullin (blood, physiology)
• Animals
• Aorta (metabolism)
• Apolipoproteins E (deficiency)
• Atherosclerosis (pathology, prevention & control)
• Calcitonin Receptor-Like Protein
• Diet, Atherogenic
• Dyslipidemias (etiology)
• Intracellular Signaling Peptides and Proteins (physiology)
• Male
• Membrane Proteins (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• RNA, Messenger (metabolism)
• Receptor Activity-Modifying Proteins
• Receptors, Adrenomedullin
• Receptors, Calcitonin (physiology)
• Receptors, Peptide (metabolism)