GE-ASSOSIATED ASPECTS OF THE EXPRESSION OF HUMAN ENDOTHELIAL SIGNAING MOLECULES AND THEIR ROLE IN THE DEVELOPMENT OF CARDIO-VASCULAR PATHOLOGY

DOI: https://doi.org/None

V.M. Soldatov (1), K.L. Kozlov (1), N.S. Linkova (1,2) 1 -Saint Petersburg Institute of Bioregulation and Gerontology, Dunamo pr, 3, Saint Petersburg, 197110, Russian Federation; 2 -Peter the Great Saint Petersburg Polytechnic University, Polytechnicheskaya str., 29, Saint Petersburg, 195251, Russian Federation

Introduction. Age-assosiated endothelial changes are one of the reasons of the development of cardio-vascular pathology. Moreover, molecular mechanisms of human endothelium aging are investigated only slightly. Thus, the problem of pathogenesis of cardio-vascular diseases is not clear yet. The goal of this work is investigation of age-dependent peculiarities of the expression of human endothelial signaling molecules. Methods. There was used autopsy material of the aorta of young, middle, elderly, senile and long-liver patients. For investigation of endothelial signal molecules expression there was used immunohistochemistry method with morphometry for the quantitative data analysis. Results. VCAM-1 and Р-selectin expression has increased by 4 times in endothelial cells of elderly and old people. The expression of PCNA proliferative protein in endothelium of elderly, old and long-liver patients decreased by 3,7 times and expression of proapoptotic protein Caspase-3 increased by 3,5 times. The expression Histone deacetilases Sirt1 and Sirt6 was decreased by 5 and 3 times in endothelium of elderly, old and longliver patients in comparison with endothelium of young and middle-aged cases. Conclusion. People older 60 years were shown to have the decreasing of functional activity and cell renovation of vessel endothelium. Moreover, endothelium adhesion ability is decreasing during aging. Age-dependent decreasing of sirtuins expression is the marker of endothelium cell senescence, which was characterized by accumulation of DNA damage. It is shown the increasing of cardio-vascular pathology risk probability in elderly and old people. Signaling molecules, which were described in this article, can be used as molecular markers for predictive diagnostics of cardio-vascular pathology.
Keywords: 
vessels, immunohistochemistry, aging, signaling molecules

Список литературы: 
  1. Belousov S.S., Novikov I.I. Rol` molekulyarno-immunologicheskih narusheniy v patogeneze infarkta miokarda i ih modulyacii v klinicheskoy praktike. Medicinskiy al`manah. 2010; 11 (2): 66–9. [Belousov S.S., Novikov I.I. The role of molecular-immunology disorders in myocardial infarction pathogenesis and its modulation in clinical practice. Medical Almanach. 2010; 11 (2): 66–9 (in Russian)]
  2. Havinson V.H., Lin`kova N.S., Morozova E.A., Gutop E.O., Elashkina E.V. Molekulyarnye mehanizmy serdechno-sosudistoy patologii. Uspehi fiziologicheskih nauk. 2014; 45 (3): 57–63. [Khavinson V.Kh., Linkova N.S., Morozova E.A., Gutop E.O., Elashkina E.V. Molecular mechanisms of cardio-vascular pathology. Achievements of Physiological Sciences. 2014; 45 (3): 57–63 (in Russian)]
  3. Lim M.A., Townsend R.R. Arterial compliance in the elderly: its effect on blood pressure measurement and cardiovascular outcomes. Clin. Geriatr Med. 2009; 25: 191–205.
  4. Bileckiy S.V. E`ndotelial`naya disfunkciya i patologiya serdechno-sosudistoy sistemy. Vnutrennyaya medicina. 2008; 2 (8): 134–9. [Biletskij S.V. Endothelial disfunction and cardiovascular system pathology. Internal Medicine. 2008; 2 (8): 134–9 (in Russian)]
  5. Gavrilova N.E., Metel`skaya V.A., Perova N.V. Vzaimosvyaz` mezhdu vyrazhennost`yu koronarnogo ateroskleroza, faktorami riska i markerami ateroskleroticheskogo porazheniya karotidnyh i perifericheskih arteriy. Kardiovaskulyarnaya terapiya i profilaktika. 2013; 12 (1): 40–5. [Gavrilova N.E., Metelskaya V.A., Petrova N.V. Correlation between intensity of coronary atherosclerosis, rick factors and markers of atheroscklerosis pathology carotid and peripherical arteries. Cardiovascular therapy and prophylactic. 2013; 12 (1): 40–5 (in Russian)]
  6. Pal`cev M.A., Kvetnoy I.M., Polyakova V.O., Gurko G.I., Mursalov S.U. Neyroimmunoe`ndokrinnye mehanizmy stareniya i vozrastnoy patologii. SPb: Nauka, 2012; 463. [Paltsev M.A., Kvetnoy I.M., Ployakova V.O., Gurko G.I., Mursalov S.U. Neuro-immuno-endocronology mechanisms of aging and age-related diseases. St. Perersburg, Russia: Nauka, 2012; 463 (in Russian)]
  7. Khavinson V.Kh., Lin’kova N.S., Elashkina E.V., Durnova A.O., Kozlov K.L. Molecular Aspects of Anti-Atherosclerotic Effects of Short Peptides. Cell. Technologies in Biology and Medicine. 2014; 158 (1): 159–63.
  8. Pal`cev M.A., Kvetnoy I.M. Rukovodstvo po neyroimmunoe`ndokrinologii. 3-e izd. M.: Shiko, 2014; 756. [Paltsev M.A., Kvetnoy I.M. The application of neuro-immuno-endocrinology. the 3rd ed. Moscow, Russia: Shiko, 2014; 756 (in Russian)]
  9. Patel N., Duffy B., Badar A., Lythgoe M., Årstad E. Bimodal Imaging of Inflammation with SPECT/CT and MRI using Iodine-125 Labelled VCAM-1 targeting Microparticle Conjugates. Bioconjug Chem. 2015; 23: 1245–9.
  10. Kubota T., Katou Y., Nakato R., Shirahige K., Donaldson A.D. Replication-Coupled PCNA Unloading by the Elg1 Complex Occurs Genome-wide and Requires Okazaki Fragment Ligation. Cell Rep. 2015; S2211-1247(15)00704-4.
  11. Ran K. Zou D.Q., Xiao Y.Y., Chang Y.T., Duan K.M., Ou Y.W., Li Z.J. Effects of isoflurane preconditioning in the delayed phase on myocardial tumor necrosis factor alpha levels and caspase-3 protein expression in a rabbit model of ischemia-reperfusion injury. Genet Mol Res. 2015; 14 (3): 7267–73.
  12. Chen J., Xavier S., Moskowitz-Kassai E., Chen R., Lu C.Y., Sanduski K., Špes A., Turk B., Goligorsky M.S. Cathepsin cleavage of sirtuin 1 in endothelial progenitor cells mediates stress-induced premature senescence. Am. J. Pathol. 2012; 180 (3): 973–83.
  13. Donato A.J., Magerko K.A., Lawson B.R., Durrant J.R., Lesniewski L.A., Seals D.R. SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans. J. Physiol. 2011; 589 (18): 4545–54.
  14. Lee O.H., Kim J., Kim J.M., Lee H., Kim E.H., Bae S.K., Choi Y., Nam H.S., Heo J.H. Decreased expression of sirtuin 6 is associated with release of high mobility group box-1 after cerebral ischemia. Biochem. Biophys Res Commun. 2013; 438 (2): 388–94.
  15. Ruan Y., Dong C., Patel J., Duan C., Wang X., Wu X., Cao Y., Pu L., Lu D., Shen T., Li J. SIRT1 suppresses doxorubicin-induced cardiotoxicity by regulating the oxidative stress and p38MAPK pathways. Cell. Physiol. Biochem. 2015; 35 (3): 1116–24.
  16. Souza J., Sousa J.R., Hirai K.E., Silva L.M., Fuzii H.T., Dias L.B. Jr., Carneiro F.R., Aarão T.L., Quaresma JA. E-selectin and P-selectin expression in endothelium of leprosy skin lesions. Acta Trop. 2015; 149: 227–31.