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(Circulation Research. 1995;77:445-465.)
© 1995 American Heart Association, Inc.

Articles

The Intima

Soil for Atherosclerosis and Restenosis

Stephen M. Schwartz, Denis deBlois, Edward R. M. O'Brien

From the Department of Pathology, University of Washington, Seattle.

Correspondence to Dr Stephen M. Schwartz, MD, PhD, Department of Pathology, University of Washington, Vascular Biology/Box 357335, Seattle, WA 98195-7335.

Key Words: intima • atherosclerosis • restenosis

	Introduction

 
Thirty years ago, John French wrote a seminal review describing the unique properties of the arterial intima.¹ His major point was that the smooth muscle cells of the intima have a unique morphology (Fig 1). French also pointed out that intimal formation appeared during normal development and aging as well as in the response of arteries to almost any imaginable injury, including atherosclerosis.

View larger version (0K): [in this window] [in a new window]   Figure 1. Top left, Histology of intima vs media. Coronary artery is from an adult patient with idiopathic dilated cardiomyopathy. In the absence of atherosclerosis, there remains diffuse intimal hyperplasia. The intima is several cell layers thick and composed of smooth muscle cells and is separated from the distinct media by the internal elastic lamina (arrows) (hematoxylin and eosin, original magnification x200). Top right, Advanced atherosclerosis of the left circumflex coronary artery. This lesion was treated by percutaneous balloon angioplasty 23 days before the patient's death. Note the complex nature of the lesion with a distinct fibrous cap (FC), intimal hyperplasia (IHP), intramural hemorrhage (H), and a necrotic core (NC) composed of inflammatory cells and accumulated lipid (hematoxylin and eosin, original magnification x100). Bottom left, Myxomatous tissue. Directional coronary atherectomy specimen from a restenotic lesion shows stellate-shaped smooth muscle cells. Smooth muscle cells with this appearance are often regarded as evidence of proliferation. Note the homogeneity of these cells and the absence of inflammatory and endothelial cells in this region (hematoxylin and eosin, original magnification x200). Bottom right, Directional coronary atherectomy specimen from a primary lesion. . . . [Full Text of this Article]

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				S. Usui, N. Sugimoto, N. Takuwa, S. Sakagami, S. Takata, S. Kaneko, and Y. Takuwa Blood Lipid Mediator Sphingosine 1-Phosphate Potently Stimulates Platelet-derived Growth Factor-A and -B Chain Expression through S1P1-Gi-Ras-MAPK-dependent Induction of Kruppel-like Factor 5 J. Biol. Chem., March 26, 2004; 279(13): 12300 - 12311. [Abstract] [Full Text] [PDF]

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				J. P. Dina, T. Feres, A. C.M. Paiva, and T. B. Paiva Role of Membrane Potential and Expression of Endothelial Factors in Restenosis After Angioplasty in SHR Hypertension, January 1, 2004; 43(1): 131 - 135. [Abstract] [Full Text] [PDF]

				F. D. Kolodgie, H. K. Gold, A. P. Burke, D. R. Fowler, H. S. Kruth, D. K. Weber, A. Farb, L.J. Guerrero, M. Hayase, R. Kutys, et al. Intraplaque Hemorrhage and Progression of Coronary Atheroma N. Engl. J. Med., December 11, 2003; 349(24): 2316 - 2325. [Abstract] [Full Text] [PDF]

				S. Fujiyama, K. Amano, K. Uehira, M. Yoshida, Y. Nishiwaki, Y. Nozawa, D. Jin, S. Takai, M. Miyazaki, K. Egashira, et al. Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells Circ. Res., November 14, 2003; 93(10): 980 - 989. [Abstract] [Full Text] [PDF]

				H. Hao, G. Gabbiani, and M.-L. Bochaton-Piallat Arterial Smooth Muscle Cell Heterogeneity: Implications for Atherosclerosis and Restenosis Development Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1510 - 1520. [Abstract] [Full Text] [PDF]

				J. E. Leidenfrost, M. F. Khan, K. P. Boc, B. R. Villa, E. T. Collins, W. C. Parks, D. R. Abendschein, and E. T. Choi A Model of Primary Atherosclerosis and Post-Angioplasty Restenosis in Mice Am. J. Pathol., August 1, 2003; 163(2): 773 - 778. [Abstract] [Full Text] [PDF]

				H.-I Yeh, C.-S. Lu, Y.-J. Wu, C.-C. Chen, R.-C. Hong, Y.-S. Ko, M.-S. Shiao, N. J. Severs, and C.-H. Tsai Reduced Expression of Endothelial Connexin37 and Connexin40 in Hyperlipidemic Mice: Recovery of Connexin37 After 7-Day Simvastatin Treatment Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1391 - 1397. [Abstract] [Full Text] [PDF]

				R. C.M Siow, C. M Mallawaarachchi, and P. L Weissberg Migration of adventitial myofibroblasts following vascular balloon injury: insights from in vivo gene transfer to rat carotid arteries Cardiovasc Res, July 1, 2003; 59(1): 212 - 221. [Abstract] [Full Text] [PDF]

				E. B. Uglow, S. Slater, G. B. Sala-Newby, C. M. Aguilera-Garcia, G. D. Angelini, A. C. Newby, and S. J. George Dismantling of Cadherin-Mediated Cell-Cell Contacts Modulates Smooth Muscle Cell Proliferation Circ. Res., June 27, 2003; 92(12): 1314 - 1321. [Abstract] [Full Text] [PDF]

				J. M. Carton, D. J. Uhlinger, A. D. Batheja, C. Derian, G. Ho, D. Argenteri, and M. R. D'Andrea Enhanced Serine Palmitoyltransferase Expression in Proliferating Fibroblasts, Transformed Cell Lines, and Human Tumors J. Histochem. Cytochem., June 1, 2003; 51(6): 715 - 726. [Abstract] [Full Text] [PDF]

				M. Hilker, T. Langin, U. Hake, F.-X. Schmid, W. Kuroczynski, H.-A. Lehr, H. Oelert, and M. Buerke Gene expression profiling of human stenotic aorto-coronary bypass grafts by cDNA array analysis Eur. J. Cardiothorac. Surg., April 1, 2003; 23(4): 620 - 625. [Abstract] [Full Text] [PDF]

				T. M. DOHERTY, P. K. SHAH, and T. B. RAJAVASHISTH Cellular origins of atherosclerosis: towards ontogenetic endgame? FASEB J, April 1, 2003; 17(6): 592 - 597. [Full Text] [PDF]

				M. Qin, Z. Zeng, J. Zheng, P. K. Shah, S. M. Schwartz, L. D. Adams, and B. G. Sharifi Suppression Subtractive Hybridization Identifies Distinctive Expression Markers for Coronary and Internal Mammary Arteries Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 425 - 433. [Abstract] [Full Text] [PDF]

				R. Wessely, L. Hengst, B. Jaschke, F. Wegener, T. Richter, R. Lupetti, M. Paschalidis, A. Schomig, R. Brandl, and F.-J. Neumann A central role of interferon regulatory factor-1 for the limitation of neointimal hyperplasia Hum. Mol. Genet., January 15, 2003; 12(2): 177 - 187. [Abstract] [Full Text] [PDF]

				J. C. Teeters, C. Erami, H. Zhang, and J. E. Faber Systemic alpha 1A-adrenoceptor antagonist inhibits neointimal growth after balloon injury of rat carotid artery Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H385 - H392. [Abstract] [Full Text] [PDF]

				H. Li, P. Dimayuga, M. Yamashita, J. Yano, M. Fournier, M. Lewis, and B. Cercek Arterial Injury in Mice with Severe Insulin-Like Growth Factor-1 (IGF-1) Deficiency Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2002; 7(4): 227 - 233. [Abstract] [PDF]

				R. L. Geary, J. M. Wong, A. Rossini, S. M. Schwartz, and L. D. Adams Expression Profiling Identifies 147 Genes Contributing to a Unique Primate Neointimal Smooth Muscle Cell Phenotype Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 2010 - 2016. [Abstract] [Full Text] [PDF]

				A. Zalewski, Y. Shi, and A. G. Johnson Diverse Origin of Intimal Cells: Smooth Muscle Cells, Myofibroblasts, Fibroblasts, and Beyond? Circ. Res., October 18, 2002; 91(8): 652 - 655. [Full Text] [PDF]