Expression Profiling Identifies 147 Genes Contributing to a Unique Primate Neointimal Smooth Muscle Cell Phenotype

Abstract

Objective-This study represents the first in an effort to systematically characterize different intimas by using expression array analysis. Methods and Results-We compared smooth muscle cells (SMCs) of the neointima formed 4 weeks after aortic grafting with those from normal aorta and vena cava from cynomolgus monkeys. Hybridization to cDNA arrays identified subsets of 147 and 45 genes differentially expressed in the neointima versus the aorta and vena cava, respectively. The expression pattern differentiating neointima from aortic SMCs was characterized largely by suppression. Only 13 genes were induced in the neointima: 7 encoded matrix proteins (6 collagens and 1 versican) and 2 encoded inducers of matrix synthesis (osteoblast-specific factor-2/Cbfa1 and connective tissue growth factor). The genes suppressed most in the neointima included the regulator of G-protein signaling-5, SPARClike-1/hevin, and nonmuscle myosin heavy chain-B. A smaller gene set differentiated the neointima from the vena cava. Most were induced (39 of 45 genes), and overlap with the neointima-aorta set was significant (10 of 13 genes). Array results were validated with Northern analysis, in situ hybridization, or immunohistochemistry. Conclusions-These data underscore the importance of matrix synthesis in neointimal maturation, and novel genes, newly associated with neointimal SMCs (regulator of G-protein signaling-5 and osteoblast-specific factor-2/Cbfa1), have raised new hypotheses regarding the pathogenesis of intimal hyperplasia. (Arterioscler Thromb Vasc

Arterial Smooth Muscle Cell Heterogeneity

“…102 Other studies with microarray techniques or differential-display polymerase chain reaction have been performed with SMCs in various situations, yielding identification of numerous, differentially expressed genes in monkeys and humans. [103][104][105] They are either unknown or known to be involved in atherosclerotic processes. A very recent study with suppressive subtractive hybridization that was performed in the pig has compared the coronary artery, predisposed to atherosclerosis, with the mammary artery, which is resistant to atherosclerosis.…”

The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis

“…Thirteen genes were upregulated in the neo-intima. Seven of these 13 genes encoded for matrix proteins (six collagens and one versican) and two genes encoded for known inducers of matrix synthesis (Cbfa1 and connective tissue growth factor) [10].…”

Emerging roles of CCN proteins in vascular development and pathology

“…Similarly, CCN2 is expressed at very high levels within atherosclerotic plaques of mice (Geary et al 2002) and atherosclerotic, but not normal human blood vessels (Oemar et al 1997). While CCN2 has been shown to be important for VSMC growth and migration and neointimal thickening in a rat carotid artery angioplasty model (Rodriguez-Vita et al 2005), the exact signaling pathways used by CCN2 by VSMC in active diseases, such as MI or atherosclerosis, have not been completely elucidated.…”