This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is uncertain whether selective injury to specific vascular sites is due to primary abnormalities of immune function or abnormalities that first appear within the once normal vessel that invited an immuno-inflammatory response. Prior studies, that have evaluated the pathogenesis of giant cell arteries, (GCA) have focused mostly on description of the inflammatory events within the vessel wall. However, the question of why selective vessel targeting occurs or what acquired vessel changes lead to triggering disease in specific vessels has not been addressed. Inherent structural and functional properties of the target organ may also contribute to the development of tissue damage and different clinical phenotype to determine whether acquired abnormalities within the vessel wall precede and are required for inflammatory injury (vacuities) in GCA of the elderly. Hypothesis: Selective organ targeting in GCA is triggered by changes in the vessel wall that may include altered gene or protein profiles. Such changes may have endogenous or exogenous origins. If intact segments of inflamed arteries are systematically examined and compared to age and gender matched normal control vessels, unique genomic patterns may identify the initial events in the pathogenesis of GCA. The inflammatory process affecting the vessel wall in GCA is often discontinuous. We are presuming that apparently normal segments of temporal artery, referred to as skip lesions , that are adjacent to areas damaged by inflammation, will reveal initial abnormalities in the vessel wall that invite an injurious reaction. In this study, we propose to use microarray techniques to specifically investigate variations in gene expression patters of skip lesions of temporal arteries from patients with biopsy-proven GCA and compare them to age, gender and ethnicity matched controls.
Specific Aims : 1. Identify gene expression patters of skip lesions in temporal arteries affected by GCA. Compare gene profiles of temporal arteries in GCA to control specimens, matched for age, gender and ethnicity to identify distinct vessel substrate fingerprints that may be the initial sep in driving inflammatory injury. 2. To validate the data obtained from microarray analysis in specific aim 1 by independent approach using Real Time Quantitative PCR technique.
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