Cytomegalovirus infection and atherosclerosis risk: A meta‐analysis

Abstract

Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta-analysis. Relative literature was searched through the electronic databases PubMed, Embase, and CNKI. Data were accurately assessed and analyzed independently by two investigators. Ultimately, the 30 studies, involving 3328 cases and 2090 controls were included in our meta-analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively, 63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were, respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26% (28/229) in control subjects. The positive ratio of HCMV infection was higher in atherosclerosis group than that in non-atherosclerosis group. Especially in Asian group, calculated odds ratios for the presence of HCMV infection in IgG-based HCMV tests, IgM-based tests, PCR-based tests, and pp65-based tests, expressed as OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09-4.51), 8.92(95%CI 3.17-25.11), 6.75 (95%CI 3.50-13.02), and 5.72(95%CI 1.51-21.58), respectively. The meta-analysis results showed that HCMV infection is significant connected with an increased risk for AS.

Productive Cytomegalovirus Infection Is Associated With Impaired Endothelial Function in ST-Elevation Myocardial Infarction

“…56 Evaluation of the immune response to cytomegalovirus infection initially did not reveal an effect of seropositivity to cytomegalovirus on the development of atherosclerosis. 13,14,57 However, the results of seroepidemiological studies were also controversial, with further studies that found a positive correlation between the increased titer of antibodies to cytomegalovirus and the development of atherosclerosis, [23][24][25]58,59 cardiovascular events, 60,61 and mortality, 62,63 even when adjusted to other traditional cardiovascular risk factors. These controversies in seroepidemiological studies as well as the low level of cytomegaloviral DNA found in atherosclerotic plaques and later in peripheral blood mononuclear cells of patients with cardiovascular diseases 64 could be explained by the occasional detection of the latent infection in these studies, rather than productive viral infection, whereas only the latter correlates with plaque destabilization.…”

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

“…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 . ECs, leukocytes, and intimal smooth muscle cells are the major players in the development of this disease .…”

“…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 …”

“…A recent meta-analysis showed that HCMV infection was also an important risk factor for atherosclerosis. 53 ECs, leukocytes, and intimal smooth muscle cells are the major players in the development of this disease. 54 As such, HCMV is also a candidate in the etiology of CVDs.…”

“…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.…”