High prevalence of human cytomegalovirus in carotid atherosclerotic plaques obtained from Russian patients undergoing carotid endarterectomy.
BACKGROUND
Human cytomegalovirus (HCMV) infection is associated with cardiovascular disease (CVD) but the role of this virus in CVD progression remains unclear. We aimed to examine the HCMV serostatus in Russian patients (n = 90) who had undergone carotid endarterectomy (CEA) and controls (n = 82) as well as to determine the prevalence of HCMV immediate early (IE) and late (LA) antigens in carotid atherosclerotic plaques obtained from 89 patients. In addition, we sought to determine whether HCMV infection was associated with inflammatory activity in the plaque by quantifying infiltrating CD3 and CD68 positive cells and 5-LO immunoreactivity.


METHODS
HCMV serology was assessed with ELISA and immunohistochemistry staining was performed to detect HCMV antigens, CD3, CD68 and 5-LO reactivity. The Fisher's exact test was used to compare i) seroprevalence of HCMV IgG between patients and controls and ii) HCMV-positive or -negative to that of CD3, CD68 and 5-LO immunoreactive cells in plaque samples. The student-t test was performed to connote the significance level of mean optical density between patients and controls.


RESULTS
The seroprevalence for HCMV IgG was high in both patients and controls (99% and 98%, respectively). Controls had significantly higher IgG titers for HCMV compared with patients (p = 0.0148). Strikingly, we found a high prevalence of HCMV antigens in atherosclerotic plaques; 57/89 (64%) and 47/87 (54%) were HCMV IE and LA positive, respectively. Most plaques had rather low HCMV reactivity with distinct areas of HCMV-positive cells mainly detected in shoulder regions of the plaques, but also in the area adjacent to the necrotic core and fibrous cap. In plaques, the cellular targets for HCMV infection appeared to be mainly macrophages/foam cells and smooth muscle cells. HCMV-positive plaques trended to be associated with increased numbers of CD68 positive macrophages and CD3 positive T cells, while 5-LO reactivity was high in both HCMV-positive and HCMV-negative plaques.


CONCLUSIONS
In Russian patients undergoing CEA, HCMV proteins are abundantly expressed in carotid plaques and may contribute to the inflammatory response in plaques via enhanced infiltration of CD68 and CD3 cells.
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.
Koon-Chu
KC
Yaiw
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.|Almazov Federal Center for Heart, Blood and Endocrinology, St. Petersburg, Russia.
Olga
O
Ovchinnikova
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.
Chato
C
Taher
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.
Abdul-Aleem
AA
Mohammad
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.
Belghis
B
Davoudi
Almazov Federal Center for Heart, Blood and Endocrinology, St. Petersburg, Russia.
Eugene
E
Shlyakhto
Almazov Federal Center for Heart, Blood and Endocrinology, St. Petersburg, Russia.
Oxana
O
Rotar
Almazov Federal Center for Heart, Blood and Endocrinology, St. Petersburg, Russia.
Alexandra
A
Konradi
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.
Vanessa
V
Wilhelmi
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.
Afsar
A
Rahbar
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.
Lynn
L
Butler
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.
Alice
A
Assinger
Department of Medicine, Center for Molecular Medicine, CMM L8:03, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden.
Cecilia
C
Söderberg-Nauclér