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Coordination in Gene Expression during Atherogenesis

T. A. Shchelkunova1*, I. A. Morozov2, P. M. Rubtsov2,3, L. M. Samokhodskaya4, I. A. Sobenin5, A. N. Orekhov5, and A. N. Smirnov1#

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

2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991 Moscow, Russia; fax: (499) 135-1405; E-mail: rubtsov@eimb.ru

3Moscow Institute of Physics and Technology, Institutskii Pereulok 9, 141700 Dolgoprudny, Moscow Region, Russia; fax: (495) 576-0813

4Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky pr. 31/5, 119899 Moscow, Russia; fax: (495) 932-9904; E-mail: slm@fbm.msu.ru

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

* To whom correspondence should be addressed.

# Deceased.

Received March 13, 2013
General tendencies in the regulation of gene expression during atherogenesis were investigated using correlation analysis for 34 mRNA species of several functional groups. The contents of mRNA were measured by quantitative PCR in samples of human aortal intima containing no lesions or atherosclerotic lesions of types I (initial lesions), II (fatty streaks), and Va (fibroatheromas). The coupling between mRNA contents in lesions and the same mRNAs in intact tissue was found to descend in the course of the disease progression. The data are in accordance with the opinion that successive morphologic types of atherosclerotic lesions correspond to steps of atherogenesis. In addition, the contents of individual mRNA species could correlate with each other within the given sample type, the extent of this coupling rising along with the disease progression. The exception from this rule was a collapse in coupling for several functional groups of mRNA in lesions of type I. This collapse could indicate special position of these lesions in pathogenesis. Statistically significant correlations between mRNAs found in samples of all four types comprised in total about 50% of all possible correlations. 66% of these correlations were conservative, i.e. observed in at least two sample types. By coupling-strength, the studied mRNAs could be divided into four clusters whose composition significantly varied along with the disease progression. The disease progression was also associated with decline in number of regulatory factors that determine coordination in expression of the analyzed genes.
KEY WORDS: mRNA, PCR, gene expression, atherogenesis, aorta, correlation analysis

DOI: 10.1134/S0006297913080117