Association of myocardial infarction with mononuclear cell expression of the cytomegalovirus chemokine receptor US28 in patients with NIDDM.

BACKGROUND

Infectious agents have been linked to atherosclerosis and its acute manifestations; however, little is known about their influence in the context of established risk factors.

OBJECTIVE

To elucidate the role of the cytomegalovirus (CMV)-encoded chemokine receptor US28 in myocardial infarction (MI) afflicting patients with or without type II diabetes mellitus (NIDDM) on a molecular level.

PATIENTS AND METHODS

In a group of patients (n=112) with a high prevalence of NIDDM and coronary artery disease, CMV serology was performed, and mRNA expression of US28 and immediate early 1 gene as markers of CMV reactivation were analyzed in peripheral mononuclear blood cells by a nested reverse transcription-polymerase chain reaction. Moreover, transendothelial chemotaxis assays using mononuclear cells transfected with or without US28 were performed in vitro.

RESULTS

While the incidence of smoking was higher in nondiabetic patients with MI than in those without MI, significant differences in other risk factors, such as cholesterol, low density lipoprotein, fibrinogen, blood pressure, and Chlamydia pneumoniae immunoglobulin G or CMV immunoglobulin G titres, were not observed. In contrast, the levels of C-reactive protein reflecting inflammation or infection were raised in NIDDM patients with or without MI. Notably, mRNA expression of intermediate early 1 gene and US28 indicative of CMV reactivation was detected in a small subset (four of 21) of NIDDM patients with MI but not in those without MI (P<0.03). Transfection of US28 in mononuclear cells conferred transendothelial chemotaxis to monocyte chemokines, inferring a mechanism for deleterious effects of CMV under permissive conditions.

CONCLUSIONS

Results show that MI was associated with mononuclear expression of CMV genes such as functional chemokine receptor US28 in a subset of patients with NIDDM, inferring that this association may predispose to MI. Ongoing infection or inflammation in NIDDM patients as shown by increased C-reactive protein may account for susceptibility to CMV reactivation and MI.