Skip to main content
SpringerLink
Log in

Coordination in gene expression during atherogenesis

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ABCA1 and ABCG1:

ATP-binding cassette transporters A1 and G1

ACAT1:

acyl-CoA-cholesterol acyltransferase 1

ApoE:

apolipoprotein E

AR:

androgen receptor

Arom:

aromatase

CCL18:

C-C motif-containing chemokine 18

CD36, CD63, and CD68:

differentiation clusters 36, 63, and 68

CEH:

cholesteryl ester neutral hydrolase

EEA1:

early endosome antigen 1

ERα:

estrogen receptor alpha

EST:

estrogen sulfotransferase

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

GNB2L1:

guanine nucleotide-binding protein, beta-peptide 2-like 1

ICAM1:

intercellular adhesion molecule 1

Lamp 1/2:

lysosome-associated membrane glycoproteins 1 and 2

LDLR:

low density lipoprotein receptor

LXRα and LXRβ:

liver X receptors alpha and beta

p62:

ubiquitin-binding protein p62

PPARα and PPARγ:

peroxisome proliferator-activated receptors alpha and gamma

Rab5a:

Ras-related small GTPase 5A

SELE:

selectin E

SR-A:

scavenger receptor A

SR-BI:

scavenger receptor BI

SREBP1 and SREBP2:

sterol regulatory element-binding proteins 1 and 2

STS:

steroid sulfatase

TfR1:

transferrin receptor 1

TLR4:

Toll-like receptor 4

TNFα:

tumor necrosis factor alpha

VCAM1:

vascular cell adhesion molecule 1

References

  1. The Global Burden of Disease: 2004 Update, World Health Organization, Geneva, Switzerland, 2008.

  2. Hansson, G. K., and Hermansson, A. (2011) Nat. Immunol., 12, 204–212.

    Article  PubMed  CAS  Google Scholar 

  3. Smirnov, A. N. (2010) Biochemistry (Moscow), 75, 793–810.

    Article  CAS  Google Scholar 

  4. Gebbers, J.-O. (2007) Ger. Med. Sci., 5, Doc04.

    PubMed  Google Scholar 

  5. Villablanca, A. C., Jayachandran, M., and Banka, C. (2010) Clin. Sci. (Lond.), 119, 493–513.

    Article  CAS  Google Scholar 

  6. Perez-Lopez, F. R., Larrad-Mur, L., Kallen, A., Chedraui, P., and Taylor, H. S. (2010) Reprod. Sci., 17, 511–531.

    Article  PubMed  CAS  Google Scholar 

  7. Stary, H. C., Chandler, A. B., Glagov, S., Guyton, J. R., Insull, W., Jr., Rosenfeld, M. E., Schaffer, S. A., Schwartz, C. J., Wagner, W. D., and Wissler, R. W. (1994) Arterioscler. Thromb., 14, 840–856.

    Article  PubMed  CAS  Google Scholar 

  8. Stary, H. C., Chandler, A. B., Dinsmore, R. E., Fuster, V., Glagov, S., Insull, W., Jr., Rosenfeld, M. E., Schwartz, C. J., Wagner, W. D., and Wissler, R. W. (1995) Arterioscler. Thromb. Vasc. Biol., 15, 1512–1531.

    Article  PubMed  CAS  Google Scholar 

  9. Shchelkunova, T. A., Morozov, I. A., Rubtsov, P. M., Samokhodskaya, L. M., Kireev, R. A., Andrianova, I. V., Orekhov, A. N., and Smirnov, A. N. (2008) Biochemistry (Moscow), 73, 920–928.

    Article  CAS  Google Scholar 

  10. Shchelkunova, T. A., Albert, E. A., Morozov, I. A., Rubtsov, P. M., Samokhodskaya, L. M., Sobenin, I. A., Orekhov, A. N., and Smirnov, A. N. (2011) Biochemistry (Moscow), 76, 1178–1184.

    Article  CAS  Google Scholar 

  11. Ishii, T., Wallace, A. M., Zhang, X., Gosselink, J., Abboud, R. T., English, J. C., Pare, P. D., and Sandford, A. J. (2006) Eur. Respir. J., 27, 300–306.

    Article  PubMed  CAS  Google Scholar 

  12. Razzhevaikin, V. N. (2010) Zh. Obshch. Biol., 71, 75–84.

    PubMed  CAS  Google Scholar 

  13. Shchelkunova, T. A., Morozov, I. A., Rubtsov, P. M., Samokhodskaya, L. M., Andrianova, I. V., Sobenin, I. A., Orekhov, A. N., and Smirnov, A. N. (2013) Biochemistry (Moscow), 78, 463–470.

    Article  CAS  Google Scholar 

  14. Laguna, J. C., and Alegret, M. (2012) Pharmacogenomics, 13, 477–495.

    Article  PubMed  CAS  Google Scholar 

  15. Hagg, D. A., Olson, F. J., Kjelldahl, J., Jernas, M., Thelle, D. S., Carlsson, L. M., Fagerberg, B., and Svensson, P. A. (2009) Atherosclerosis, 204, e15–20.

    Article  PubMed  Google Scholar 

  16. Liu, P. Y., Christian, R. C., Ruan, M., Miller, V. M., and Fitzpatrick, L. A. (2005) J. Clin. Endocrinol. Metab., 90, 1041–1046.

    Article  PubMed  CAS  Google Scholar 

  17. Nakamura, Y., Miki, Y., Suzuki, T., Nakata, T., Darnel, A. D., Moriya, T., Tazawa, C., Saito, H., Ishibashi, T., Takahashi, S., Yamada, S., and Sasano, H. (2003) Am. J. Pathol., 163, 1329–1339.

    Article  PubMed  CAS  Google Scholar 

  18. Edfeldt, K., Swedenborg, J., Hansson, G. K., and Yan, Z. Q. (2002) Circulation, 105, 1158–1161.

    PubMed  CAS  Google Scholar 

  19. Albrecht, C., Soumian, S., Amey, J. S., Sardini, A., Higgins, C. F., Davies, A. H., and Gibbs, R. G. (2004) Stroke, 35, 2801–2806.

    Article  PubMed  CAS  Google Scholar 

  20. Mishra, A., Eathiraj, S., Corvera, S., and Lambright, D. G. (2010) Proc. Natl. Acad. Sci. USA, 107, 10866–10871.

    Article  PubMed  CAS  Google Scholar 

  21. Sedov, K. R., Gorban’, A. N., Petushkova, E. V., Manchuk, V. T., and Shalamova, E. N. (1988) Vestn. Akad. Med. Nauk SSSR, No. 10, 69–75.

    Google Scholar 

  22. Bobryshev, Iu. V., Karagodin, V. P., Kovalevskaia, Zh. I., Miasoedova, V. A., Shapyrina, E. V., Saliamov, V. I., Kargapolova, Iu. M., Galaktionova, D. Iu., Mel’nichenko, A. A., and Orekhov, A. N. (2011) Tsitologiya, 53, 815–825.

    Google Scholar 

  23. Santos, G. M., Fairall, L., and Schwabe, J. W. (2011) Trends Endocrinol. Metab., 22, 87–93.

    Article  PubMed  CAS  Google Scholar 

  24. Banos, G., Guarner, V., and Perez-Torres, I. (2011) Cardiovasc. Hematol. Agents Med. Chem., 9, 137–146.

    Article  PubMed  CAS  Google Scholar 

  25. Cho, S. (2012) Curr. Pharm. Des., 18, 3721–3730.

    Article  PubMed  CAS  Google Scholar 

  26. Archacki, S. R., Angheloiu, G., Moravec, C. S., Liu, H., Topol, E. J., and Wang, Q. K. (2012) Hum. Mol. Genet., 21, 1364–1373.

    Article  PubMed  CAS  Google Scholar 

  27. Turpeinen, H., Raitoharju, E., Oksanen, A., Oksala, N., Levula, M., Lyytikainen, L. P., Jarvinen, O., Creemers, J. W., Kahonen, M., Laaksonen, R., Pelto-Huikko, M., Lehtimaki, T., and Pesu, M. (2011) Atherosclerosis, 219, 799–806.

    Article  PubMed  CAS  Google Scholar 

  28. Zhang, J., Burridge, K. A., and Friedman, M. H. (2008) Am. J. Physiol. Heart Circ. Physiol., 295, H1556–1561.

    Article  PubMed  CAS  Google Scholar 

  29. Sluimer, J. C., Kisters, N., Cleutjens, K. B., Volger, O. L., Horrevoets, A. J., van den Akker, L. H., Bijnens, A. P., and Daemen, M. J. (2007) Physiol. Genom., 30, 335–341.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biological Faculty, Lomonosov Moscow State University, Leninsky Gory 1/12, 119899, Moscow, Russia

    T. A. Shchelkunova & A. N. Smirnov

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991, Moscow, Russia

    I. A. Morozov & P. M. Rubtsov

  3. Moscow Institute of Physics and Technology, Institutskii Pereulok 9, 141700, Dolgoprudny, Moscow Region, Russia

    P. M. Rubtsov

  4. Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky pr. 31/5, 119899, Moscow, Russia

    L. M. Samokhodskaya

  5. Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, ul. Baltiiskaya 8, 125315, Moscow, Russia

    I. A. Sobenin & A. N. Orekhov

Authors
  1. T. A. Shchelkunova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. A. Morozov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. M. Rubtsov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. M. Samokhodskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. A. Sobenin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. N. Orekhov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. N. Smirnov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. A. Shchelkunova.

Additional information

Published in Russian in Biokhimiya, 2013, Vol. 78, No. 8, pp. 1187–1200.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shchelkunova, T.A., Morozov, I.A., Rubtsov, P.M. et al. Coordination in gene expression during atherogenesis. Biochemistry Moscow 78, 933–945 (2013). https://doi.org/10.1134/S0006297913080117

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297913080117

Key words

Search

Navigation