Abstract
The long-term pathomorphological changes of the injured vessels under angiotensin-converting-enzyme (ACE) inhibitor are still not known. Therefore, we assessed the alternations of vascular architecture after three-month therapy with ACE inhibitor and identified new target cells for this medication. Carotid arteries of spontaneously hypertensive rats underwent balloon angioplasty. 14 days prior intervention, half of the animals was treated with ACE inhibitor. After three months of vascular trauma, the injured vessels were explored by histomorphology and immunohistochemistry for angiotensin-II receptor (AT1R), dendritic and HSP47+ cells. The neointimal growth decreased significantly only up to 28 days under ACE inhibitor. In contrast, the reductive effect of ACE inhibitor on media area persisted up to three months after intervention. A significant fraction of early neointimal cells was of a dendritic cell type. The relevant portion of these cells showed an expression of AT1R and HSP47. AT1R was present in 70% and HSP47 in 18% of all early neointimal cells in both groups. ACE inhibitor may at least temporarily diminish remodelling processes in injured vessels. The detection of AT1R on dendritic cells identifies these cells as important targets for therapeutic strategies involving modulation of the renin-angiotensin system.
Similar content being viewed by others
References
Eltchaninoff H., Koning R., Christphe T., Gupta V., Cribier A., Balloon Angioplasty for the treatment of Coronary In-Stent Restensosis: Immediate Results and 6-Month Angiographic Recurrent Restenosis Rate, J. Am. Coll. Cardiol., 1998, 32, 980–984
Tsang J., Sheppard R., Hou Mak K., Brown D., Huynh T., Schechter D., et al., Six-month outcomes of percutaneous transluminal coronary angioplasty in hypertensive patients: Results from the ROSETTA registry, Am. Heart. J., 2002, 1, 124–129
Cutlip D.E., Chauhan M.S., Baim D.S., Ho K.K.L., Poppma J.J., Carrozza J.P., et al., Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials, J. Am. Coll. Cardiol., 2002, 40, 2082–2089
Mehta P.K., Griendling K.K., Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system, Am. J. Physiol. Cell. Physiol., 2007, 292, C82–97
Kleinert S., HOPE for cardiovascular disease prevention with ramipril, Lancet, 1999, 354, 841
Tropeano A.I., Saleh N., Hawajri N., Macquin-Mavier I., Maison P., Do all antihypertensive drugs improve carotid intima-media thickness? A network meta-analysis of randomized controlled trials, Fundam. Clin. Pharmacol., 2011, 25, 395–404
Hanson S.R., Powell J.S., Dodson T., Lumsden A., Kelly A.B., Anderson J.S., et al., Effects of angiotensin converting enzyme inhibition with cilazapril on intimal hyperplasia in injured arteries and vascular grafts in the baboon, Hypertension, 1991, 18, II70–76
Phillips M.I., Kagiyama S., Angiotensin II as a proinflammatory mediator, Curr. Opin. Investig. Drugs, 2002, 3, 569–577
Skowasch D., Jabs A., Andrié R., Dinkelbach S., Schiele TM., Wernert N., et al., Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis. Tissue characteristics compared to primary atherosclerosis, J. Vasc. Res., 2004, 41, 525–534
Tuleta I., Skowasch D., Peuster M., Nickenig G., Bauriedel G., Cells of primarily extravascular origin in neointima formation following stent implantation: coordinated expression of endothelial progenitor, dendritic and neural crest-derived cells, Cardiology, 2008, 110, 199–205
Jandeleit-Dahm K., Burrell L.M., Johnston C.I., Koch K.M., Elevated vascular angiotensin converting enzyme mediates increased neointima formation after balloon injury in spontaneously hypertensive rats, J. Hypertens., 1997, 15, 643–650
Clozel J.P., Müller R.K., Roux S., Fischli W., Baumgartner HR., Influence of the status of the renin-angiotensin system on the effect of cilazapril on neointima formation after vascular injury in rats, Circulation, 1993, 88, 1222–1227
Schmitt R., Clozel J.P., Iberg N., Bühler FR., Prevention of neointima formation by mibefradil after vascular injury in rats: comparison with ACE inhibition, Cardiovasc. Drugs Ther., 1996, 10, 101–105
Hannan J.L., Blaser M.C., Pang J.J., Adams S.M., Pang S.C., Adams M.A., Impact of hypertension, aging, and antihypertensive treatment on the morphology of the pudendal artery, J. Sex. Med., 2011, 8, 1027–1038
Hong Y.J., Jeong M.H., Song S.J., Sim D.S., Kim J.H., Lim K.S., et al., Effects of ramiprilat-coated stents on neointimal hyperplasia, inflammation, and arterial healing in a porcine coronary restenosis model, Korean Circ. J., 2011, 41, 535–541
Tyralla K., Adamczak M., Benz K., Campean V., Gross M.L., Hilgers K.F., et al., High-dose enalapril treatment reverses myocardial fibrosis in experimental uremic cardiomyopathy, PLoS One, 2011, 6, e15287
Yilmaz R., Altun B., Kahraman S., Ozer N., Akinci D., Turgan C., Impact of amlodipine or ramipril treatment on left ventricular mass and carotid intimamedia thickness in nondiabetic hemodialysis patients, Ren. Fail., 2010, 32, 903–912
Matsuno H., Stassen J.M., Moons L., Vermylen J., Hoylaerts M.F., Neointima formation in injured hamster carotid artery is effectively prevented by the combination G4120 and quinapril, Thromb. Haemost., 1996, 76, 263–269
Kalinowski M., Tepe G., Schieber A., Brehme U., Bruck B., Erley C.M., et al., Local administration of ramiprilat is less effective than oral ramipril in preventing restenosis after balloon angioplasty in an animal model, J. Vasc. Interv. Radiol., 1999, 10, 1397–1404
Multicenter European Research Trial with Cilazapril after Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MERCATOR) Study Group. Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial, Circulation, 1992, 86, 100–110
Desmet W., Vrolix M., De Scheerder I., Van Lierde J., Willems J.L., Piessens J., Angiotensinconverting enzyme inhibition with fosinopril sodium in the prevention of restenosis after coronary angioplasty, Circulation, 1994, 89, 385–392
Fukuda D., Enomoto S., Nagai R., Sata M., Inhibition of renin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation, Biomed. Pharmacother., 2009, 63, 754–761
Śladowska-Kozłowska J., Litwin M., Niemirska A., Płudowski P., Wierzbicka A., Skorupa E., et al., Oxidative stress in hypertensive children before and after 1 year of antihypertensive therapy, Pediatr. Nephrol., 2012, 27, 1943–1951
Zhong J.C., Ye J.Y., Jin H.Y., Yu X., Yu H.M., Zhu D.L., et al., Telmisartan attenuates aortic hypertrophy in hypertensive rats by the modulation of ACE2 and profilin-1 expression, Regul. Pept., 2011, 166, 90–97
Wong J., Rauhöft C., Dilley R.J., Agrotis A., Jennings G.L., Bobik A., Angiotensin-converting enzyme inhibition abolishes medial smooth muscle PDGF-AB biosynthesis and attenuates cell proliferation in injured carotid arteries: relationships to neointima formation, Circulation, 1997, 96, 1631–1640
Hernández-Presa M.A., Bustos C., Ortego M., Tuñón J., Ortega L., Egido J., ACE inhibitor quinapril reduces the arterial expression of NF-kappaB-dependent proinflammatory factors but not of collagen I in a rabbit model of atherosclerosis, Am. J. Pathol., 1998, 153, 1825–1837
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Tuleta, I., Bauriedel, G., Krämer, S. et al. Long-term effects of ACE inhibitor on vascular remodelling. cent.eur.j.med 9, 741–747 (2014). https://doi.org/10.2478/s11536-013-0343-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2478/s11536-013-0343-6