Increased angiogenesis leading the elevated local pressure is a known factor that promotes rupture of carotid artery plaques in humans. To define the molecular mechanisms that lead to new blood vessel formation in plaques, we evaluated the gene expression profiles of carotid plaques from symptomatic stroke patients in comparison to asymptomatic patients. Of the similar to 45,000 mRNA transcripts analyzed using GeneChip microarrays, 236 were expressed at a higher level in the symptomatic plaques. Of those, we could identify 31 genes that are known to participate in cell division and new blood vessel formation. In addition, in the symptomatic plaques, the fibrous cap is significantly thinner, and the density of new vessels is significantly higher (by similar to 200 to 350%) in both the plaque proper and the fibrous cap compared to the asymptomatic plaques. This study indicates that increased angiogenesis observed in the symptomatic plaques has a molecular basis supported by elevated angiogenic gene expression.