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CARDIOPULMONARY GENE EXPRESSION PROFILES IN NORMO- AND SPONTANEOUSLY HYPERSENSITIVE (SH) RATS: IMPACT OF PARTICULATE MATTER (PM) EXPOSURE
Citation:
Nadadur, S. S. AND U P. Kodavanti. CARDIOPULMONARY GENE EXPRESSION PROFILES IN NORMO- AND SPONTANEOUSLY HYPERSENSITIVE (SH) RATS: IMPACT OF PARTICULATE MATTER (PM) EXPOSURE. Presented at American Thoracic Society Annual Meeting, San Francisco, CA, May 18-23, 2001.
Description:
CARDIOPULMONARY GENE EXPRESSION PROFILES IN NORMO- AND SPONTANEOUSLY HYPERTENSIVE (SH) RATS: IMPACT OF PARTICULATE MATTER (PM) EXPOSURE. SS Nadadur UP Kodavanti, Pulmonary Toxicology Branch, ETD, ORD, NHEERL, US Environmental Protection Agency, Research Triangle Park, NC 27711.
Cardiovascular disease is considered as one susceptibility factor for the adverse health effects of air pollutants, including ambient PM. To understand the role of underlying pathophysiology on the toxicity of PM, we utilized the SH rat, a strain genetically derived from normotensive Wistar Kyoto (WKY) rat as an animal model of hypertension and cardiac hypertrophy. Our earlier studies have demonstrated exacerbated pulmonary injury and hematological changes when SH were exposed to fugitive residual oil fly ash (ROFA). To identify the possible molecular mechanism(s) for the increased toxicity observed in SH, we utilized the rat cardiopulmonary gene array blot developed in our lab, consisting of 90 genes representing 9 functional gene clusters, to derive the expression profile in lung and left ventricle. WKY and SH were intratracheally instilled with either saline or ROFA (0.5 mg /rat) and 24h after instillation, right lung lobes and left ventricle were isolated and frozen for RNA extraction. 32P-labeled cDNA generated from the lung and the left ventricular RNA were hybridized to array blots. After high stringency wash, the blots were scanned and the density of the cDNA spots on the array were quantitated using Imagequant software. IFN-g and MIP-2 expression were high, while the levels of Troponin-1, alpha-actin cardiac protein and Ca2+-ATPase were low in the left ventricle of SH compared to WKY rats. Basal expression of IFN-g and NGF levels were high in the lungs of WKY compared to SH rats. ROFA-induced up regulation of inflammatory markers were noted in the lungs of both WKY and SH rats. The differential expression and interaction of these genes in the left ventricle and lung of SH may provide clues to our understanding on the basic mechanism(s) of PM toxicity and host susceptibility. (This abstract does not reflect USEPA policy).