Coordination in gene expression during atherogenesis.
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.
Biological Faculty, Lomonosov Moscow State University, Moscow, 119899, Russia. schelkunova-t@mail.ru.
T A
TA
Shchelkunova
I A
IA
Morozov
P M
PM
Rubtsov
L M
LM
Samokhodskaya
I A
IA
Sobenin
A N
AN
Orekhov
A N
AN
Smirnov
D000293:Adolescent; D000328:Adult; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008055:Lipids / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
D008055:Lipids; D012333:RNA, Messenger