Positive Expression of Human Cytomegalovirus Phosphoprotein 65 in Atherosclerosis

Abstract

Previous studies showed that human cytomegalovirus (HCMV) is associated with atherosclerosis. However, local vascular atherosclerosis related HCMV infection and protein expression remain unclear. This study aimed to assess the relationship between HCMV infection and atherosclerosis. Formalin-fixed, paraffin-embedded peripheral artery specimens were obtained from 15 patients with atherosclerosis undergoing vascular surgery from 2008 to 2010 at Zhongnan Hospital, Wuhan University. Pathological analyses were carried out after hematoxylin and eosin (H&E) and Masson trichrome staining. In situ hybridization and immunohistochemistry with two different monoclonal antibodies were employed to detect HCMV nucleic acids and proteins, respectively. H&E and Masson trichrome staining showed homogeneous extracellular matrix in femoral artery, while smooth muscle fibers were interlaced with collagen fibers; in carotid artery, inflammatory cell infiltration, foam cell vascular change, cholesterol crystals, and layered collagen fibers were observed. In situ hybridization showed no expression of HCMV nucleic acids in all 15 cases. Immunohistochemical staining for protein immediate-early protein (IE1 72) was negative in all cases, while phosphoprotein 65 (pp65) expression was detected in 14 cases. A high rate of positive pp65 signals was found in patients with atherosclerosis, suggesting that local HCMV infection may be associated with the pathogenesis of atherosclerosis. Further studies on this relationship are warranted.

Mechanisms of human cytomegalovirus infection with a focus on epidermal growth factor receptor interactions

“…However, there is no evidence of viral binding to these receptors in HCMV‐mediated angiogenesis. EGFR is required for the HCMV‐induced angiogenic response, whereas the Src family of tyrosine kinases is only partially required . Furthermore, EGFR‐mediated and integrin‐mediated signaling (via Src) is rapidly activated in ECs after infection, suggesting that the engagement of such signaling after viral binding is intimately associated with functional changes in ECs …”

“…51 A positive expression of pp65 was found in patients with atherosclerosis, suggesting that local HCMV infection might be associated with the pathogenesis of this disease. 52 This inflammatory artery disease that is characterized by alterations in the levels of lipids and other metabolites is the most important cause of cardiovascular diseases (CVDs). A recent meta-analysis showed that HCMV infection was also an important risk factor for atherosclerosis.…”

“…EGFR is required for the HCMVinduced angiogenic response, whereas the Src family of tyrosine kinases is only partially required. 52,53 Furthermore, EGFR-mediated and integrin-mediated signaling (via Src) is rapidly activated in ECs after infection, suggesting that the engagement of such signaling after viral binding is intimately associated with functional changes in ECs. 55 Monocytes are other primary in vivo targets for HCMV and are ing cells and to prevent the cell from responding to host EGF signaling and may drive the cell into a state that conflicts with optimal virus production.…”

Human cytomegalovirus promotes the activation of TGF-β1 in human umbilical vein endothelial cells by MMP-2 after endothelial mesenchymal transition

“…It has been found that HCMV is associated with a variety of cardiovascular diseases such as atherosclerosis (AS), coronary heart disease and hypertension. [1][2][3][4][5][6] Human cytomegalovirus infection is also related to the dysfunction of vascular endothelial cells (VECs). [7][8][9] Antiviral drugs, including ganciclovir, can reduce the risk of a heart transplant-associated AS.…”

Clinico-Immunological Features of Cerebrovascular Disease Associated With Herpetic Infection

“…Многие исследователи пытались установить связь атеросклероза с герпесвирусной инфекцией, сравнивая частоту встречаемости вирусной ДНК в атеросклеротических измененных и нормальных стенках артерий. Однако полученные результаты слишком противоречивы и требуют дальнейшего изучения [7,8]. К ранним признакам ЦВБ относят: быструю утомляемость, умеренно выраженные головные боли, раздражительность и частую смену настроения, головокружение.…”