Proliferation and extracellular matrix synthesis of smooth muscle cells cultured from human coronary atherosclerotic and restenotic lesions

Cardiac Catheterization Laboratory, Erasmus University, Rotterdam, The Netherlands.

OBJECTIVES. The purpose of this study was to examine the proliferative capacity and extracellular matrix synthesis of human coronary plaque cells in vitro. BACKGROUND. Common to both primary atherosclerosis and restenosis are vascular smooth muscle cell proliferation and production of extracellular matrix proteins. The applicability to humans of experimental animal models of these processes has been questioned. METHODS. Primary atherosclerotic and restenotic lesions were excised by percutaneous directional coronary atherectomy in 93 patients. Smooth muscle cells were cultivated by an explant technique and identified by their morphology in culture, ultrastructural features under electron microscopy and immunostaining using monoclonal antibodies to smooth muscle cell alpha-actin. Proliferation in secondary culture was assessed with growth curves and the synthesis of collagen and sulfated glycosaminoglycans by the incorporation of 3H-proline and 35S-sulfate, respectively. These studies were also performed in cells derived from human umbilical artery media. RESULTS. Success rates for primary (45%) and secondary (12%) culture of coronary cells were not influenced by clinical variables or lesion category. Primary culture success was improved by the presence of organized thrombus in the plaque and in relation to increased maximal cell density of the atherectomy specimen. Restenotic cells displayed more rapid growth than did cells of primary atherosclerotic origin, which grew in a manner similar to that of umbilical artery cells. Mean calculated population-doubling times for the three cell groups were 52 h (95% confidence interval [CI] 48 to 58 h), 71 h (95% CI 62 to 83 h) and 74 h (95% CI 65 to 84 h), respectively. Restenotic and primary atherosclerotic cells did not differ in the synthesis of collagen ([mean +/- SEM] 0.034 +/- 0.004 vs. 0.033 +/- 0.004 nmol isotope.microgram protein-1, p = NS) or sulfated glycosaminoglycans (11.47 +/- 1.07 vs. 15.37 +/- 3.10 nmol isotope.microgram protein-1, p = NS), but the coronary cells synthesized significantly more collagen and sulfated glycosaminoglycans than did umbilical artery cells (0.019 +/- 0.004 and 5.43 +/- 1.00 nmol isotope.microgram protein-1, respectively, both p < 0.05). CONCLUSIONS. These data indicate that increased smooth muscle cell proliferation contributes to coronary restenosis in humans and support the concept that the extracellular matrix synthesis of adult smooth muscle cells is important to lesion formation.

This article has been cited by other articles:

				J. S. Garanich, R. A. Mathura, Z.-D. Shi, and J. M. Tarbell Effects of fluid shear stress on adventitial fibroblast migration: implications for flow-mediated mechanisms of arterialization and intimal hyperplasia Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3128 - H3135. [Abstract] [Full Text] [PDF]

				K. M. Ainslie, J. S. Garanich, R. O. Dull, and J. M. Tarbell Vascular smooth muscle cell glycocalyx influences shear stress-mediated contractile response J Appl Physiol, January 1, 2005; 98(1): 242 - 249. [Abstract] [Full Text] [PDF]

				M. Civelek, K. Ainslie, J. S. Garanich, and J. M. Tarbell Smooth muscle cells contract in response to fluid flow via a Ca2+-independent signaling mechanism J Appl Physiol, December 1, 2002; 93(6): 1907 - 1917. [Abstract] [Full Text] [PDF]

				Q. J. Zhang, M. Goddard, C. Shanahan, L. Shapiro, and M. Bennett Differential Gene Expression in Vascular Smooth Muscle Cells in Primary Atherosclerosis and In Stent Stenosis in Humans Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 2030 - 2036. [Abstract] [Full Text] [PDF]

				S. Mochizuki, B. Brassart, and A. Hinek Signaling Pathways Transduced through the Elastin Receptor Facilitate Proliferation of Arterial Smooth Muscle Cells J. Biol. Chem., November 15, 2002; 277(47): 44854 - 44863. [Abstract] [Full Text] [PDF]

				R. Locher, R. P. Brandes, W. Vetter, and M. Barton Native LDL Induces Proliferation of Human Vascular Smooth Muscle Cells via Redox-Mediated Activation of ERK 1/2 Mitogen-Activated Protein Kinases Hypertension, February 1, 2002; 39(2): 645 - 650. [Abstract] [Full Text] [PDF]

				W. R. P. Agema, J. W. Jukema, S. N. Pimstone, and J. J. P. Kastelein Genetic aspects of restenosis after percutaneous coronary interventions;towards more tailored therapy Eur. Heart J., November 2, 2001; 22(22): 2058 - 2074. [PDF]

				E.G. Zouridakis, R. Schwartzman, X. Garcia-Moll, I.D. Cox, S. Fredericks, D.W. Holt, and J.C. Kaski Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression Eur. Heart J., September 1, 2001; 22(17): 1578 - 1584. [Abstract] [PDF]

				P. H. Grewe, T. Deneke, A. Machraoui, J.u. Barmeyer, and K.-M. Muller Acute and chronic tissue response to coronary stent implantation: pathologic findings in human specimen J. Am. Coll. Cardiol., January 1, 2000; 35(1): 157 - 163. [Abstract] [Full Text] [PDF]

				A. J. Wardeh, I. P. Kay, M. Sabate, V. L. M. A. Coen, A. L. Gijzel, J. M. R. Ligthart, A. den Boer, P. C. Levendag, W. J. van der Giessen, and P. W. Serruys {beta}-Particle-Emitting Radioactive Stent Implantation : A Safety and Feasibility Study Circulation, October 19, 1999; 100(16): 1684 - 1689. [Abstract] [Full Text] [PDF]

				C. M. Castro, M. C. Cruzado, R. M. Miatello, and N. R. Risler Proteoglycan Production by Vascular Smooth Muscle Cells From Resistance Arteries of Hypertensive Rats Hypertension, October 1, 1999; 34(4): 893 - 896. [Abstract] [Full Text] [PDF]

				J.-M. Li and G. Brooks Cell cycle regulatory molecules (cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors) and the cardiovascular system; potential targets for therapy? Eur. Heart J., March 2, 1999; 20(6): 406 - 420. [PDF]

				A. Kastrati, A. Schomig, M. Seyfarth, W. Koch, S. Elezi, C. Bottiger, J. Mehilli, K. Schomig, and N. von Beckerath PlA Polymorphism of Platelet Glycoprotein IIIa and Risk of Restenosis After Coronary Stent Placement Circulation, March 2, 1999; 99(8): 1005 - 1010. [Abstract] [Full Text] [PDF]

				H. Suzuki, S. Kawai, T. Aizawa, K. Kato, S. Sunayama, R. Okada, and H. Yamaguchi Histological evaluation of coronary plaque in patients with variant angina: relationship between vasospasm and neointimal hyperplasia in primary coronary lesions J. Am. Coll. Cardiol., January 1, 1999; 33(1): 198 - 205. [Abstract] [Full Text] [PDF]

				J M Mann, J C Kaski, W I Pereira, S Arie, J A Ramires, and F Pileggi Histological patterns of atherosclerotic plaques in unstable angina patients vary according to clinical presentation Heart, July 1, 1998; 80(1): 19 - 22. [Abstract] [Full Text]

				H.-I Yeh, F. Lupu, E. Dupont, and N. J. Severs Upregulation of Connexin43 Gap Junctions Between Smooth Muscle Cells After Balloon Catheter Injury in the Rat Carotid Artery Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 3174 - 3184. [Abstract] [Full Text]

				H. Ueba, M. Kawakami, and T. Yaginuma Shear Stress as an Inhibitor of Vascular Smooth Muscle Cell Proliferation : Role of Transforming Growth Factor-ß1 and Tissue-Type Plasminogen Activator Arterioscler. Thromb. Vasc. Biol., August 1, 1997; 17(8): 1512 - 1516. [Abstract] [Full Text]

				J. Gunn, C. M. Holt, S. E. Francis, L. Shepherd, M. Grohmann, C. M. H. Newman, D. C. Crossman, and D. C. Cumberland The Effect of Oligonucleotides to c-myb on Vascular Smooth Muscle Cell Proliferation and Neointima Formation After Porcine Coronary Angioplasty Circ. Res., April 19, 1997; 80(4): 520 - 531. [Abstract] [Full Text]

				A. Nagler, H.-Q. Miao, H. Aingorn, M. Pines, O. Genina, and I. Vlodavsky Inhibition of Collagen Synthesis, Smooth Muscle Cell Proliferation, and Injury-Induced Intimal Hyperplasia by Halofuginone Arterioscler. Thromb. Vasc. Biol., January 1, 1997; 17(1): 194 - 202. [Abstract] [Full Text]