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Changes in Levels of Gene Expression in Human Aortal Intima during Atherogenesis

T. A. Shchelkunova1, I. A. Morozov2, P. M. Rubtsov2, L. M. Samokhodskaya3, I. V. Andrianova4, I. A. Sobenin5, A. N. Orekhov5, and A. N. Smirnov1*

1Biological Faculty, Lomonosov Moscow State University, Leninsky Gori 1/12, 119899 Moscow, Russia; fax: (495) 939-4309; E-mail: smirnov__an@mail.ru

2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119899 Moscow, Russia; fax: (499) 135-1405; E-mail: rubtsov@eimb.ru

3Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky pr. 31/5, 119899 Moscow, Russia; fax: (495) 932-9904; E-mail: slm@fbm.msu.ru

4Russian Cardiological Scientific Production Complex, 3-ya Cherepkovskaya ul. 15A, 121552 Moscow, Russia; fax: (495) 414-6731; E-mail: irandrianova@yandex.ru

5Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, 125315 Moscow, Russia; fax: (495) 415-9594; E-mail: office@inat.ru

* To whom correspondence should be addressed.

Received December 17, 2012; Revision received January 21, 2013
Changes in the contents of 36 mRNAs species related to lipid turnover, inflammation, metabolism and the action of sex hormones in samples of aortal intima along the “intact tissue – lesions of type I – lesions of type II – lesions of type Va” sequence were analyzed using quantitative PCR. The expression of several mRNAs coding for components of the vesicular transfer and lipid turnover machinery was found to be resistant to atherogenesis or even decline in the course of atherogenesis. Decrease in expression was also recorded for steroid sulfatase, androgen receptor, and low density lipoprotein receptor mRNAs. However, the contents of the majority of other mRNA species increased gradually during disease progression. The earliest changes found as early as in lesions of type I were characteristic for estrogen sulfotransferase, apolipoprotein E, scavenger receptor SR-BI, collagen COL1A2, as well as chemokine CCL18 mRNAs. The contents of several mRNAs in intact tissue and atherosclerotic injuries had gender differences. Additionally, responses of two mRNAs, for aromatase and sterol regulatory element binding protein 2, to atherosclerotic lesion were also sex-differentiated. The contents of the majority of analyzed mRNAs in peripheral blood monocyte-derived macrophages were higher than in intact aorta. The correlations found in atherosclerotic lesions between mRNA species that predominant in macrophages and those expressed at comparable levels in macrophages and intact aorta or mainly in aorta suggest that the observed rise in the content of the majority of mRNAs during atherogenesis is determined by increase in expression in resident cells. The data suggest that the revealed absence of homeostatic regulation of expression of a number of genes associated with vesicular transfer and lipid turnover can serve as one of the reasons for lysosomal function insufficiency that leads to foam cell formation in atheroma. The observed sex differences in expression of a number of mRNAs suggest that estrogens in women perform their atheroprotective effects starting with predisposition to the disease and finishing with advanced stages of the pathologic process.
KEY WORDS: mRNA, PCR, gene expression, atherogenesis, aorta, gender differences, macrophages

DOI: 10.1134/S0006297913050040