Abstract
Aim:
To explore the effects of cariporide on the expression of intercellular adhesion molecule-1 (ICAM-1) and the adhesion of monocytes to vascular smooth muscle cells (SMC) in vitro.
Methods:
Monocytes were isolated from human peripheral blood by the Ficoll-Hypaque method. The expression of ICAM-1 in SMC was detected by ELISA. The adhesion of monocytes to SMC was stimulated by lysophosphatidylcholine (LPC). The adhesion ratio of monocytes was assayed by measuring protein contents. The intracellular pH ([pH]i) of SMC was measured with 2′,7′-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF).
Results:
Preincubation of SMC with LPC alone (5 μg/mL) for 4 h markedly enhanced the expression of ICAM-1 in SMC and the rate of the adhesion of monocytes to SMC in a concentration-dependent and time-related manner. LPC simultaneously also induced an increase of [pH]i value in SMC. Cariporide concentration-dependently reduced the adhesion ratio of monocytes to SMC and the expression of ICAM-1 in SMC induced by LPC. The inhibitory effects of cariporide on the expression of ICAM-1 in SMC and the adhesion of monocytes to SMC also were associated with blocking LPC-induced elevation of the [pH]i value in SMC.
Conclusion:
LPC-induced monocyte-SMC adhesion may be mediated via activation of the Na+/H+ (NHE) exchanger. The action mechanism of cariporide may be related with inhibition of activation of the Na+/H+ exchanger of plasma membranes and ICAM-1 expression on the surface of SMC induced by LPC.
Similar content being viewed by others
Article PDF
References
Gan XT, Chakrabarti S, Karmazyn M . Modulation of Na+/H+ exchange isoform 1 mRNA expression in isolated rat hearts. Am J Physiol 1999; 277: H993–8.
Linz WJ, Busch AE . NHE-1 inhibition: from protection duringacute ischaemia/reperfusion to prevention/reversal of myocardial remodeling. Naunyn Schmiedebergs Arch Pharmacol 2003; 368: 239–46.
Karmazyn M, Sawyer M, Fliegel L . The Na(+)/H(+) exchanger: a target for cardiac therapeutic intervention. Curr Drug Targets Cardiovasc Haematol Disord 2005; 5: 323–35.
Karmazyn M . Pharmacology and clinical assessment of cariporide for the treatment of coronary artery diseases. Expert Opin Investig Drugs 2000; 9: 1099–108.
Tu JH, Liu LY . Selective sodium/hydrogen exchanger inhibitor HOE642 inhibited proliferation of vascular smooth muscle cells. Chin J Pharmacol Toxicol 2001; 15: 260–4.
Wang SX, Xiong XM, Song T, Liu LY . Protective effects of cariporide on endothelial dysfunction induced by high glucose. Acta Pharmacol Sin 2005; 26: 329–33.
Tu JH, Liu LY, Zhang XH . Protective effect of Na(+)-H+exchanger inhibitor cariporide on the injury of vascular endothelial function induced by hypercholesterolemia. J Hu-nan Med Univ 2002; 27: 13–6 ( in Chinese).
Ross R . The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature 1993; 362: 801–9.
Gouni-Berthold I, Sachinidis A . Possible non-classic intracellularand molecular mechanisms of LDL cholesterol action contributing to the development and progression of atherosclerosis. Curr Vasc Pharmacol 2004; 2: 363–70.
Scalia R, Murohara T, Campbell B, Kaji A, Lefer AM . Lysophos-phatidylcholine stimulates leukocyte rolling and adherence in ratmesenteric microvasculature. Am J Physiol 1997; 272: H2584–90.
Watanabe T, Pakala R, Katagiri T, Benedict CR . Lysophosphatidylcholine is a major contributor to the synergistic effect of mildly oxidized low-density lipoprotein with endothelin-1 on vascular smooth muscle cell proliferation. J Cardiovasc Pharmacol 2002; 39: 449–59.
Fogelman AM, Elahi F, Sykes K, Van Lenten BJ, Territo MC, Berliner JA . A modification of the Recalde method for the isolation of human monocytes. J Lipid Res 1988; 29: 1243–7.
Territo MC, Berliner JA, Almada L, Ramirez R, Fogelman AM . β-very low density lipoprotein pretreatment of endothelial mono-layers increases monocyte adhesion. Atherosclerosis 1989; 9: 824–8.
Bradford MM . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–54.
Pigott R, Needham LA, Edwards RM, Walker C, Power C . Structural and functional studies of the endothelial activation antigen endothelial leukocyte adhesion molecule-1 using a panel of monoclonal antibodies. J Immunol 1991; 147: 130–5.
Rink TJ, Tsien RY, Pozzan T . Cytoplasmic pH and free Mg2+ inlymphocytes. J Cell Biol 1982; 95: 189–96.
Thomas JA, Buchsbaum RN, Zimniak A, Racker E . Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ. Biochemistry 1979; 18: 2210–8.
Chin B, Lip GY . Cariporide aventis. Curr Opin Investig Drugs 2000; 1: 340–6.
Kinard F, Jaworski K, Sergent-Engelen T, Goldstein D, Van Veldhoven PP, Holvoet P, et al. Smooth muscle cells influence monocyte response to LDL as well as their adhesion and transmigration in a coculture model of the arterial wall. J Vasc Res 2001; 38: 479–91.
Morelli PI, Martinsson S, Ostergren-Lunden G, Friden V, Moses J, Bondjers G, et al. IFN gamma regulates PDGF-receptor alpha expression in macrophages, THP-1 cells, and arterial smooth muscle cells. Atherosclerosis 2006; 184: 39–47.
Gan XT, Chakrabarti S, Karmazyn M . Modulation of Na+/H+exchange isoform 1 mRNA expression in isolated rat hearts. Am J Physiol 1999; 277: H993–8.
Jung O, Albus U, Lang HJ, Busch AE, Linz W . Effects of acute and chronic treatment with the sodium hydrogen exchanger 1(NHE-1) inhibitor cariporide on myocardial infarct mass in rabbits with hypercholesterolaemia. Basic Clin Pharmacol Toxicol 2004; 95: 24–30.
Koliakos G, Zolota Z, Paletas K, Kaloyianni M . High glucose concentrations stimulate human monocyte sodium/hydrogen exchanger activity and modulate atherosclerosis-related functions. Pflugers Arch 2004; 449: 298–306.
Kaloyianni M, Zolota Z, Paletas K, Tsapas A, Koliakos G . Cariporide counteracts atherosclerosis-related functions in monocytes from obese and normal individuals. Obes Res 2005; 13: 1588–95.
Lee KU, Lee IK, Han J, Song DK, Kim YM, Song HS, et al. Effects of recombinant adenovirus-mediated uncoupling protein 2 over expression on endothelial function and apoptosis. Circ Res 2005; 96: 1200–7.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by the National Natural Science Foundation of China (No 39770857).
Rights and permissions
About this article
Cite this article
Li, Z., Song, T., Liu, Gz. et al. Inhibitory effects of cariporide on LPC-induced expression of ICAM-1 and adhesion of monocytes to smooth muscle cells in vitro. Acta Pharmacol Sin 27, 1326–1332 (2006). https://doi.org/10.1111/j.1745-7254.2006.00412.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2006.00412.x
Keywords
This article is cited by
-
Geomorphology-oriented digital terrain analysis: Progress and perspectives
Journal of Geographical Sciences (2021)