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Home > Medical Professionals > Research Initiatives Conference > Poster Abstracts Accepted > Benharash Differential Gene Expression

Differential Gene Expression in Outward vs. Inward Arterial Remodeling

Peyman Benharash, Chengpei Xu, Jean Picquet, Oscar J Abilez, Monica Divakaruni, Philip Tsao, Christopher K Zarins
Stanford University, Stanford, CA

Objectives: Uncontrolled outward arterial remodeling (aneurysm formation) and uncontrolled inward remodeling (intimal hyperplasia and stenosis) represent the major mechanisms of vascular disease. We compared gene expression in experimental models of outward remodeling (high flow AV fistula) and inward remodeling (balloon injury) to determine the similarities and differences. Methods: We constructed carotid-jugular AVF in 10 rats and performed carotid balloon injury in 10 rats. Carotid blood flow was measured at baseline and after 2 days, animals were sacrificed and carotid arteries harvested. Real-time PCR was used to evaluate gene expression from extracted RNA in the general areas of cell cycle (p21), inflammation (COX2, NOX2), and matrix remodeling (MMP 2, 12). Expression parameters were normalized to internal and external standards. Results: Carotid blood flow decreased after balloon injury (from 6 to 4 ml/min) and increased 7 fold after AVF (p < 0.001). P21 and MMP12 expression increased in both models while expression behavior in the other areas is shown in table 1.COX2 and NOX2 trends were divergent at 2 days. Conclusions: At 2 days, outward and inward remodeling appear to be very different processes at the genetic level. While they share proliferation and remodeling signals, inflammation appears dominant in the balloon injury model, while a reduction in inflammation in the AVF model is likely due to increased shear (athero-protective). Further analysis of candidate genes will provide new insights into vascular remodeling. Blocking the inflammatory cascade early after ballooning may be crucial to prevention of intimal hyperplasia after angioplasty.

TABLE 1:

	Gene Expression at 2-days (folds over control)
	P21 (cell cycle)	NOX2 (oxidation)	COX2 (inflammation)	MMP2 (gelatinase)	MMP12 (elastase)
Balloon Injury	1.5 ± 0.38	7.8 ± 7	1.1 ± 0.78	0.65 ± 0.19	2.9 ± 2.5
p-value	0.002	0.01	0.75	0.002	0.04
AV Fistula	1.5 ± 0.5	1.0 ± 0.3	0.22 ± 0.1	0.87 ± 0.25	3.0 ± 0.74
p-value	0.02	0.94	0.01	0.43	<0.0001