adrenomedullin and Coronary-Restenosis

The authors determined the changes in adrenomedullin (AM) expression in the coronary circulation of patients with ischemic heart disease who underwent coronary stent implantation. Blood samples were drawn from the coronary sinus before, immediately after and four hours after coronary stent implantation, and plasma levels of AM were measured. AM levels in the coronary sinus blood were significantly increased four hours after stent implantation. On the other hand, in the femoral arterial blood, no significant changes in AM levels were observed. A significant positive correlation was found between AM level in the coronary sinus blood four hours after stent implantation and late loss index six months after the procedure. These results suggest that inflammation after coronary stent implantation induces AM expression, which might play an important role in restenosis after stenting.

Topics: Adrenomedullin; Angioplasty, Balloon, Coronary; Case-Control Studies; Coronary Angiography; Coronary Circulation; Coronary Restenosis; Coronary Stenosis; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Peptides; Prognosis; Stents; Time Factors; Vasodilator Agents

Although drug-eluting stents (DES) have been widely used for the treatment of coronary artery disease, they potentially increase the risk of late thrombosis. It is, therefore, desirable to establish a strategy to stimulate reendothelialization. Endothelial injury models have been widely used to analyze the mechanisms of coronary restenosis. However, animal models deployed with coronary stents in the blood vessels are necessary to accurately analyze the mechanisms of coronary restenosis and late thrombosis because persistent inflammation occurs around the coronary stents.. Coronary stents were implanted into rat abdominal aorta and adipose tissue-derived stem cells (ASC) were administered from the adventitial side. Reendothelialization was then visualized by Evans blue staining, and neointimal formation was analyzed histologically. ASC significantly stimulated reendothelialization and inhibited neointimal formation in bare metal stents (BMS)-implanted aorta. In addition, ASC promoted reendothelialization in DES-implanted aorta; however, the effects were weaker than in BMS-implanted aorta. Among the cytokines that ASC produce, adrenomedullin (AM) significantly stimulated reendothelialization and inhibited neointimal formation in BMS-implanted aorta, when an adenovirus expressing AM was administered from the adventitial side.. These results suggest that ASC produce several cytokines that stimulate reendothelialization and inhibit neointimal formation in stent-deployed vessels, and that AM could mediate these effects.

Topics: Adipose Tissue; Adrenomedullin; Animals; Aorta, Abdominal; Cells, Cultured; Coronary Restenosis; Disease Models, Animal; Male; Neointima; Rats; Rats, Wistar; Stem Cell Transplantation; Stem Cells; Stents

To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty.. In rat aortic artery restenosis model produced by denudation of aortic endothelia, we observed changes of endothelin (ET), angiotensin II (AII), calcitonin gene-related peptide (CGRP) and adrenomedullin (Adm) in plasma and aorta with radioimmunoassay and expression of hypertension-related gene (HRG-1) with semi-quantitative RT-PCR, and studied the effects of these peptides on intimal hyperplasia, intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore, in cultured cells, we studied the effects of these peptides on vascular smooth muscle cell (VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with 3H-TdR incorporation and RT-PCR respectively.. After angioplasty, the levels of ET and AII in plasma and aorta significantly increased, accompanied with VSMC proliferation and neointima hyperplasia. On day 10 after angioplasty, the levels of ET in plasma and aorta increased by 69% and 124% respectively, compared with sham group (P < 0.01); and the level of aortic AII increased by 80% (P < 0.01). Antiserum against ET or inhibitors of angiotensin converting enzyme (ACE) could significantly inhibit the proliferation of VSMC and neointima formation. Compared with the sham group, on day 3 after angioplasty, the CGRP levels in plasma and aorta increased by 64% and 89% respectively (P < 0.01) and the Adm levels in plasma and tissue increased by 129% and 102% respectively (P < 0.01). On day 10, intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima formation induced by balloon aortic injury (by 66% and 79% respectively, P < 0.01). In addition, ET and AII attenuated the expression of HRG-1 in aorta and stimulated mitogen-activated protein kinase (MAPK) activity, while CGRP and Adm potentiated the expression of HRG-1 and inhibited MAPK.. ET and AII can stimulate the proliferation of injured intima while CGRP and Adm have an anti-hyperplasia effect after angioplasty. These 4 peptides are involved in the regulation of VSMC proliferation and affect the development of vascular restenosis by regulating the expression of HRG-1 and MAPK activity.

Topics: Adrenomedullin; Angioplasty, Balloon; Angiotensin II; Animals; Aorta, Thoracic; Calcitonin Gene-Related Peptide; Cell Division; Cells, Cultured; Coronary Restenosis; Endothelin-1; Male; Mitogen-Activated Protein Kinases; Muscle, Smooth, Vascular; Peptides; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Vasodilator Agents

To investigate the effects of several vasoactive peptides on the development of restenosis.. The model of balloon angioplasty to the rat aorta was prepared and used to study the changes of endothelin (ET), angiotensin II (A II), calcitonin gene-related peptide (CGRP) and adrenomedullin (Adm) in the plasma and aorta tissues, with radioimmuno-assay. (3)H-TdR incorporation and intima/media ratio of aortic tissue were measured after angioplasty. In cultured vascular smooth muscle cells, effects of these peptides on the proliferation of VSMC were evaluated with (3)H-TdR incorporation. Effects of these peptides on the expression of hypertension-related gene (HRG-1) in aorta tissue and cultured VSMC from SHR and WKY rats were studied by semi-quantitative RT-PCR.. After angioplasty, the levels of ET and A II in the plasma and/or aorta tissue were significantly increased, with VSMC proliferation. On day 10 after angioplasty, the levels of ET in the plasma and tissue were increased by 69% and 124% respectively, compared with the that in the control group (P < 0.01); and the levels of aortic A II were increased by 80% (P < 0.01). Antiserum against ET and angiotensin converting enzyme (ACE) inhibitors could obviously inhibit the proliferation of VSMC and neointima formation. Compared with the sham group on day 3 after angioplasty, the CGRP levels in plasma and aorta tissue were increased by 64% and 89% respectively (P < 0.01); the Adm levels in the plasma and aorta tissue were increased by 129% and 102% respectively (P < 0.01). On day 10, intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima formation induced by balloon aortic injury with the inhibitory rate of 66% and 79%, respectively, (P < 0.01). ET and A II attenuated the expression of HRG-1 in the aorta, thus activating mitogen activated protein kinase (MAPK). CGRP and Adm potentiated the expression of HRG-1, thus inhibiting the activity of MAPK.. ET and A II stimulate the proliferation of injured intima, and CGRP and Adm have an anti-hyperplasia effects after angioplasty. That these peptides are suggested to be involved in the regulation of proliferation of VSMC and to affect the developing of vascular restenosis, by means of regulating the expression of HRG-1 and MAPK activities.

Topics: Adrenomedullin; Angiotensin II; Animals; Calcitonin Gene-Related Peptide; Cell Division; Coronary Restenosis; Endothelins; Mitogen-Activated Protein Kinases; Muscle, Smooth, Vascular; Peptides; Rats; Tunica Intima