adrenomedullin and Aortic-Diseases

The aim of the present study was to investigate the effect of adrenomedullin (ADM) on vascular calcification.. The vascular calcification model was established in rats (VND group) by using vitamin D3 (300,000 IU/kg) and nicotine (25 mg/kg, two doses). The effect of liposome-encapsulated ADM was observed. Vascular calcium content, alkaline phosphatase (ALP) activity, ADM in aortic tissue and plasma, binding ability of 125I-ADM for ADM receptor on vascular plasma membrane and content of cAMP in vessels were measured.. Compared with control rats, the aortic calcium content and vascular ALP activity in rats of the VDN group was obviously increased; in addition ADM concentrations in plasma and vessels of rats in VDN group were increased. But the maximum binding sites of 125I-ADM for ADM receptor (Bmax) on vascular plasma membrane in rats of VDN group were significantly decreased compared with control rats. The affinity of 125I-ADM for the ADM receptor was reduced, as shown by the Kd value and vascular cAMP content being reduced in rats of the VDN group compared to the control group. The in vitro response of isolated vessels to ADM incubation was weakened. Administration of empty liposome had no effect on vascular calcification. But administration of ADM significantly decreased vascular calcium content and ALP activity. The Bmax of 125I-ADM for ADM receptors on vascular plasma membrane increased by 17.7% (p < 0.01), and the value of Kd decreased by 36.2% (P < 0.01) in rats treated with ADM as compared with rats of the VDN group. In addition, the vascular cAMP content and the response to ADM in isolated aorta were markedly increased.. Vascular calcification induced an alteration of the vascular ADM-ADM receptor-cAMP pathway. Treatment with exogenous ADM inhibited vascular calcification by improving the vascular ADM-ADM receptor-cAMP pathway.

Topics: Adrenomedullin; Alkaline Phosphatase; Animals; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Calcinosis; Calcium; Culture Techniques; Cyclic AMP; Disease Models, Animal; Liposomes; Male; Myocardium; Peptides; Rats; Rats, Wistar; Receptors, Adrenomedullin; Receptors, Peptide

There is evidence that adrenomedullin has autocrine or paracrine activities that oppose cardiac remodelling. However, it remains unclear whether it exerts those local functions in heart failure patients.. To investigate the relation between plasma and pericardial fluid concentrations of adrenomedullin and left ventricular haemodynamic variables.. Samples of plasma and pericardial fluid were obtained from 50 patients undergoing cardiac surgery. They were classified into two groups: group N (n = 27) with a left ventricular end diastolic volume index (LVEDVI) < or = 90 ml/m(2); and group R (n = 23) with LVEDVI > 90 ml/m(2). Plasma and pericardial fluid concentrations of total adrenomedullin (tAM) and mature adrenomedullin (mAM) were measured and related to the preoperative haemodynamic variables.. Pericardial fluid concentrations of mAM were much higher than the plasma concentration in both group N and group R (mean (SEM), 10.6 (1.7) v 3.3 (0.2) fmol/ml, p = 0.0001; and 21.2 (2.8) v 3.9 (0.3) fmol/ml, p < 0.0001, respectively). The ratio mAM/tAM in pericardial fluid was significantly higher than in plasma (0.56 (0.02) v 0.28 (0.02), p < 0.0001). Pericardial fluid concentrations of mAM, but not plasma concentrations, were significantly correlated with LVEDVI, left ventricular end systolic volume index, left ventricular ejection fraction, and left ventricular mass index (r = 0.60, 0.63, -0.54, and 0.47, respectively).. Raised pericardial fluid concentrations of mAM may reflect the actions of adrenomedullin as a local mediator against cardiac remodelling in patients with left ventricular dysfunction.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Aorta, Thoracic; Aortic Diseases; Biomarkers; Body Fluids; Female; Heart Diseases; Humans; Male; Middle Aged; Peptides; Pericardium; Ventricular Dysfunction, Left; Ventricular Remodeling

Macrophages secrete a variety of growth factors, cytokines and vasoactive peptides, which are related to the progression of atherosclerosis. Adrenomedullin (ADM) is a potent vasodilator peptide and inhibits proliferation and migration of vascular smooth muscle cells. In this study, we investigated the production and secretion of ADM by monocytes and macrophages by Northern blot analysis, RIA and immunocytochemistry. Northern blot analysis showed that ADM mRNA was expressed in human monocytes obtained from peripheral blood and monocyte-derived macrophages. The expression level of ADM mRNA in monocyte-derived macrophages was about five times higher than that in monocytes. Treatment with lipopolysaccharide (100 ng/ml) for 24 h increased ADM mRNA expression levels in both monocytes and monocyte-derived macrophages. The levels of immunoreactive ADM in the media of monocyte-derived macrophages were about three times higher than that of monocytes (0. 718+/-0.046 fmol/24 h/10(5) cells, n=8 compared with 0.259+/-0.018 fmol/24 h/10(5) cells, n=8; mean+/-S.E.M., P<0.01). The secretion was also increased by treatment with lipopolysaccharide. Immunocytochemistry showed positive ADM immunostaining in macrophages in atherosclerotic lesions of human aorta obtained at autopsy. ADM secreted from activated macrophages may play an inhibitory role in atherogenesis.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Aortic Diseases; Arteriosclerosis; Blotting, Northern; Cell Culture Techniques; Chromatography, High Pressure Liquid; Female; Humans; Immunoenzyme Techniques; Macrophages; Male; Middle Aged; Monocytes; Peptides