adrenomedullin and Aortic-Aneurysm--Abdominal

Prospective clinical plasma biomarker studies in abdominal aortic aneurysm (AAA) pathogenesis have been hampered by the need for very large cohorts and long follow-up time. The main aim of the present study was to evaluate the association of adrenomedullin, a cardiovascular (CV) stress marker, and incident AAA risk. Prospective longitudinal cohort of middle-aged individuals from the CV cohort of the Malmö Diet and Cancer Study (n = 5551; 1991-1994) was assessed. Plasma concentrations of midregional proadrenomedullin (MR-proADM), C-reactive protein (CRP), and conventional risk factors were measured at baseline. Incidence of AAA was studied up to December 31, 2013. Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry, and AAA was diagnosed on average 14 years later. Adjusting for age, gender, smoking, body mass index, hypertension, diabetes mellitus, and CRP, MR-proADM (hazard ratio: 1.28; 95% confidence interval: 1.01-1.62) was independently associated with incident AAA. The plasma biomarker MR-proADM seems to be a marker of AAA risk, implying that AAA development may be driven by long-standing CV stress on the aortic wall.

Topics: Adrenomedullin; Aortic Aneurysm, Abdominal; Biomarkers; C-Reactive Protein; Female; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Protein Precursors; Risk Factors; Sweden; Time Factors

Produced by vascular walls, adrenomedullin (AM) exerts antifibrotic actions in the process of cardiovascular remodeling. The purpose of this study was to examine the pathophysiological role of AM in the development of human abdominal aortic aneurysm (AAA).. Immunohistochemical analyses revealed that vascular smooth muscle cells in the media were positive for AM in the early stage of atherosclerotic aorta. Intense immunoreactivity was observed in mast cells of the outer media and adventitia of AAA, and the number of mast cells was greater (p < 0.01) in AAA than in atherosclerotic aorta without any aneurysmal change. To determine the role of AM in mast cells, we examined cultured human mast cell leukemia line-1 (HMC-1) and fibroblasts isolated from AAA patients. Cultured HMC-1 cells were found to express preproAM gene and release AM peptide into the cultured media. When assessed by collagenase-sensitive [3H]proline incorporation and procollagen type I C-peptide secretion, collagen synthesis in co-culture of HMC-1 and the fibroblasts was reduced by 10(-6) mol/L synthetic AM, while conversely, it increased following blockade of the action of endogenous AM with 10 microg/mL anti-AM monoclonal antibody.. The present study suggests an anti-fibrotic role for AM released from mast cells, providing new insight into the biological actions of mast cell-derived AM in the development of AAA.

Topics: Adrenomedullin; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Atherosclerosis; Cell Line, Tumor; Cells, Cultured; Collagen; Fibrosis; Humans; Immunohistochemistry; Mast Cells; Peptides; Protein Biosynthesis; Protein Precursors; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger