Abstract
Atherosclerosis is a complicated process, involving genetic and methabolic factors, associated with the interactions
between cells of many different types. Mechanisms of plaque destabilization are still not clear and require
new investigations. Connections between human herpes viruses (HHV) and atherosclerosis were suggested in 19th
century. However, in spite of many studies on the do not know wether HHV play a role in atherosclerosis development
and progression since the results of these studies are highly controversial. According to some studies the
relations between HHV infection and atherosclerosis exist, but other studies do not confirm this result. Also, controvercial
data were published on the prevalence of HHV in atherosclerosis: this prevalence varied 0 to 100%. No
doubt that we need further investigations that include determination of the latency/activity of HHV not only in
tissue but also in blood of the patients with atherosclerosis.
References
1. Murray C.J., Lopez A.D. Alternative projections of
mortality and disability by cause 1990–2020:
Global Burden of Disease Study. Lancet. 1997; 349:
1498–504.
2. Montalescot G., Sechtem U. Stable Coronary Artery
Disease (Management of) ESC Clinical Practice
Guidelines; 2013.
3. Finn A.F., Nakano M., Narula J., Kolodgie F.D.,
Renu Virmani R. Concept of vulnerable/unstable
plaque. Arterioscler. Thromb. Vasc. Biol. 2010; 30:
1282–92.
4. Hartvigsen K., Chou M.Y., Hansen L.F. et al. The
role of innate immunity in atherogenesis. J. Lipid.
Res. 2009; 50 (Suppl.): 388.
5. De Palma R., Del Galdo F., Abbate G. Patients with
acute coronary syndrome show oligoclonal T-cell
recruitment within unstable plaque: evidence for a
local, intracoronary immunologic mechanism.
Circulation. 2006; 113: 640–6.
6. Ferrante G., Nakano M., Virmani R., Crea F. et al.
High levels of systemic myeloperoxidase are associated
with coronary plaque erosion in patients with
acute coronary syndromes: a clinicopathological
study. Circulation. 2010; 112: 213–28.
7. Gilbert A., Lion G. Arterites infectieuses experimentales.
C. R. Hebd. Seances. Mem. Soc. Biol. 1889; 41:
583–4.
8. Campbell L.A., Yaraei K., Van Lenten B., Chait A.,
Blessing E., Kuo C.C. The acute phase reactant
response to respiratory infection with Chlamydia
pneumoniae: implications for the pathogenesis of
atherosclerosis. Microbes Infect. 2010; 12:
598–606.
9. Ford P.J., Gemmell E., Timms P., Chan A., Preston
F.M., Seymour G.J. Anti-P. gingivalis response
correlates with atherosclerosis. J. Dent. Res. 2007;
86: 35–40.
10. Kowalski M. Helicobacter pylori (H. pylori) infection
in coronary artery disease: influence of
H. pylori eradication on coronary artery lumen
after percutaneous transluminal coronary angioplasty.
The detection of H. pylori specific DNA in
human coronary atherosclerotic plaque. J. Physiol.
Pharmacol. 2001; 52: 3–31.
11. Alyan O., Kacmaz F., Ozdemir O. Hepatitis C infection
is associated with increased coronary artery
atherosclerosis defined by modified Reardon severity
score system. Circulation. 2008; 72: 1960–5.
12. Frenkel N., Schirmer E., Wyatt L., Katsofanas G.,
Roffman E., Danovich R., June C. Isolation of a new
herpesvirus from human CD41 T cells. Proc. Natl.
Acad. Sci. USA. 1990; 87: 748–52.
13. Ryan K.J., Ray C.G. Sherris Medical Microbiology
(4th ed.). McGraw Hill; 2004.
14. Adams M.J., Carstens E.B. Ratification vote on taxonomic
proposals to the International Committee
on Taxonomy of Viruses. Arch. Virol. 2012; 157 (7):
1411–22.
15. Whitley R.J. Herpesviruses. In: Baron S. (ed).
Medical Microbiology. 4th ed. Univ of Texas
Medical Branch; 1996.
16. Murray P.R., Rosenthal K.S., Pfaller M.A. Medical
Microbiology. 5th ed. Elsevier Mosby; 2005.
17. Fabricant C.G., Fabricant J., Minick C.R., Litrenta
M.M. Herpesvirus-induced atherosclerosis in
chickens. Fed. Proc. 1983; 42: 2476–9.
18. Chu A., Prasad J. Antagonism by IL-4 and IL-10 of
endotoxin-induced tissue factor activation in
monocytic THP-1 cells: activating role of CD14 ligation.
J. Surg. Res. 1998; 80: 80–7.
19. Hajjar D. Viral pathogenesis of atherosclerosis:
impact of molecular mimicry and viral genes. Am.
J. Pathol. 1991; 139: 1195–211.
20. DuRose J., Li J., Chien S., Spector D. Infection of vascular
endothelial cells with human cytomegalovirus
under fluid shear stress reveals preferential entry and
spread of virus in flow conditions simulating atheroprone
regions of the artery. J. Virol. 2012; 24:
13745–55.
21. Melnick J.L., Hu C. Cytomegalovirus DNA in arterial
walls of patients with atherosclerosis. J. Med.
Virol. 1994; 42 (2): 170–4.
22. Shi Y., Tokunaga O. Herpesvirus HSV-1, EBV and
CMV infections in atherosclerotic compared with
non-atherosclerotic aortic tissue. Pathol. Int. 2002;
52 (1): 31–9.
23. Radke P.W., Merkelbach-Bruse S. Direct evidence
of cytomegalovirus in coronary atheromas of
patients with advance coronary heart artery disease.
Med. Klin. (Munich). 2001; 96 (3): 129–34.
24. Virok D., Kis Z., Kari L. Chlamydophila pneumoniae
and human cytomegalovirus in atherosclerotic
carotid plaques-combined presence and possible
interactions. Acta Microbiol. Immunol. Hung. 2006;
53 (1): 35–50.
25. Xenaki E., Hassoulas J. Detection of cytomegalovirus
in atherosclerotic plaques and nonatherosclerotic
arteries. Angiology. 2009; 60 (4): 504–8.
26. Westphal M., Lautenschlager I. Cytomegalovirus
and proliferative signals in the vascular wall of
CABG patients. Thorac. Cardiovasc. Surg. 2006;
54 (4): 219–26.
27. Kotronias D., Kapranos N. Herpes simplex virus as a
determinant risk factor for coronary artery
atherosclerosis and myocardial infarction. In Vivo.
2005; 19 (2): 351–7.
28. Schlitt A., Blankenberg S., Weise K., Gärtner B.C.,
Mehrer T., Peetz D., Meyer J., Darius H., Rupprecht
H.J. Herpesvirus DNA (Epstein–Barr virus,
herpes simplex virus, cytomegalovirus) in circulating
monocytes of patients with coronary artery disease.
Acta Cardiol. 2005; 60 (6): 605–10.
29. Voorend M., van der Ven A.J. Limited role for C.
pneumoniae, CMV and HSV-1 in cerebral large
and small vessel atherosclerosis. Open Neurol. J.
2008; 2: 39–44.
30. Reszka E., Jegier B. Detection of infectious agents
by polymerase chain reaction in human aortic wall.
Cardiovasc. Pathol. 2008; 17 (5): 297–302.
31. Grose C., Adams H.P. Reassessing the link between
herpes zoster ophthalmicus and stroke. Expert Rev.
Anti Infect. Ther. 2014; 12 (5): 527–30.
32. Ibrahim A.I., Obeid M.T. Detection of herpes simplex
virus, cytomegalovirus and Epstein–Barr virus
DNA in atherosclerotic plaques and in unaffected
bypass grafts. J. Clin. Virol. 2005; 32 (1): 29–32.
33. Nagel M.A., Choe A., Khmeleva N., Overton L., Rempel
A., Wyborny A., Traktinskiy I., Gilden D. Search
for varicella zoster virus and herpes simplex virus-1
in normal human cerebral arteries. J. Neurovirol.
2013; 19 (2): 181–5.
34. Kaklikkaya I., Kaklikkaya N. Detection of human
herpesvirus 6 DNA but not human herpesvirus 7 or 8
DNA in atherosclerotic and nonatherosclerotic vascular
tissues. Heart Surg. Forum. 2010; 13 (5): 345–9.
35. Ye D., Nichols T.C. Absence of human herpesvirus 8
genomes in coronary atherosclerosis in immunocompetent
patients. Am. J. Cardiol. 1997; 79 (9):
1245–7.
36. Magnoni M., Malnati M., Cristell N., Coli S., Russo
D., Ruotolo G., Cianflone D., Alfieri O., Lusso P.,
Maseri A. Molecular study of human herpesvirus 6 and
8 involvement in coronary atherosclerosis and coronary
instability. J. Med. Virol. 2012; 84 (12): 1961–6.
37. Yi L., Wang D.X., Feng Z.J. Detection of human
cytomegalovirus in atherosclerotic carotid arteries
in humans. J. Formos. Med. Assoc. 2008; 107 (10):
774–81.
38. Roizman B., Whitley R.J. An inquiry into the molecular
basis of HSV latency and reactivation. Annu.
Rev. Microbiol. 2013; 67: 355–74.
39. Yasuda C., Okada K., Ohnari N., Akamatsu N.,
Tsuji S. Cerebral infarction and intracranial
aneurysm related to the reactivation of varicella
zoster virus in a Japanese acquired immunodeficiency
syndrome (AIDS) patient. Rinsho
Shinkeigaku. 2013; 53 (9): 701–5.
40. Schädlich H.J., Nekic M., Jeske J., Karbe H.
Intrathecal humoral immune reaction in zoster
infections. J. Neurol. Sci. 1991; 103 (1): 101–4.
41. Hagiwara N., Toyoda K. Lack of association
between infectious burden and carotid atherosclerosis
in Japanese patients. J. Stroke Cerebrovasc.
Dis. 2007; 16 (4): 145–52.
42. Zhou Y.F., Guetta E., Yu Z.X. et al. Human
cytomegalovirus increases modified low density
lipoprotein uptake and scavenger receptor mRNA
expression in vascular smooth muscle cells. J. Clin.
Invest. 1996; 98: 2129–38.
43. Burnett M.S., Durrani S., Stabile E. et al. Murine
cytomegalovirus infection increases aortic expression
of proatherosclerosis genes. Circulation. 2004;
109: 893–7.
44. Grivel J.C., Ivanova O., Pinegina N., Blank P.S.,
Shpektor A., Margolis L.B., Vasilieva E. Activation
of T lymphocytes in atherosclerotic plaques.
Arterioscler. Thromb. Vasc. Biol. 2011; 31 (12):
2929–37.
45. Morré S.A., Stooker W., Lagrand W.K., van den
Brule A.J.C., Niessen H.W.M. Microorganisms in
the aetiology of atherosclerosis. J. Clin. Pathol.
2000; 53: 647–54.
46. Vercellotti G.M. Effects of viral activation of the vessel
wall on inflammation and thrombosis. Blood
Coagul. Fibrinolysis. 1998; 2: S3–6.
47. Flamand L., Lautenschlager I., Krueger G.,
Dharam A. (eds) Human herpesviruses HHV-6A,
HHV-6B & HHV-7: Diagnosis and clinical management.
Elsevier Science; 2014.
48. Ingianni A., Madeddu M.A., Carta F., Reina A.,
Lai C., Pompei R. Epidemiology of human herpesvirus
type 8 infection in cardiopathic patients.
Online J. Biol. Sci. 2009; 9 (2): 36–9.
49. Никитская Е.А., Гривель Ж.-Ш., Иванова О.И.,
Лебедева А.М., Шпектор А.В., Марголис Л.Б.,
Васильева Е.Ю. Исследование герпесвирус-
ной ДНК в коронарных артериях пациентов,
умерших в острой стадии инфаркта миокарда.
Креативная кардиология. 2014; 4: 52–64 /
Nikitskaya E.A., Grivel'J.-C., Ivanova O.I.,
Lebedeva A.M., Shpektor A.V., Margolis L.B.,
Vasil'eva E.Yu. Detection of human herpes viruses
DNA in coronary artery in patients who died in
acute stage of myocardial infarction. Kreativnaya
Kardiologiya. 2014; 4: 52–64 (in Russian).
50. Benditt E.A, Barrett T., McDougall J.K. Viruses in
the etiology of atherosclerosis. Proc. Natl. Acad. Sci.
USA. 1983; 80: 6386–9.
