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In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute.).

The results from this first population-based cohort study of CMV infection and carotid IMT are compatible with the hypothesis of a causal role of CMV in atherosclerosis.

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The biological properties of cytomegalovirus (CMV) are consistent with a potential role in the pathogenesis of atherosclerosis. The evidence of such a role has so far been circumstantial, but CMV nucleic acid is beginning to be reported with increasing frequency in the arterial wall. Arterial specimens from 135 patients who underwent vascular surgery for symptomatic atherosclerotic vessel disease were analyzed by PCR for the presence of CMV nucleic acid. Samples were studied from the atheromatous plaque area and from uninvolved aortic tissues of patients undergoing surgery for vascular disease. One primer pair (LA) was used for detection of a late gene, and two other primer pairs (E1 and E2) were used for the immediate early gene region. Serum antibody to CMV was measured by radioimmunoassay. With the late gene primer, CMV nucleic acid was found in 76% of the tissue specimens tested, whereas the E2 gene primer complementary to the transforming mtr2 region was reactive in 90% of the arterial samples. There was no significant difference in the prevalence of CMV DNA in atherosclerotic plaque tissue and in uninvolved aortic tissue from the patients. A second early gene primer was not reactive with the tissue specimens, although it gave positive results with the positive control of infectious virus. Serum antibody to CMV was detected in 86% of the patients in whose tissue CMV DNA was demonstrated. CMV DNA was detected in a high proportion of atherosclerotic plaque tissues as well as in uninvolved aortic tissue of surgical patients, suggesting that latent CMV infection of the arterial wall may be a common occurrence in patients with atherosclerosis.

Finding that an avian herpesvirus can cause atherosclerosis in chickens prompted studies of human herpesviruses in human atherosclerosis. Antigens and nucleic acid sequences of cytomegalovirus (CMV), a widespread member of the herpesvirus family, were found in arterial lesions in human atherosclerosis, but infectious virus has not been observed. In atherosclerosis patients, high levels of CMV antibodies are present, suggesting the presence of virus that had been activated from a latent state. Atherosclerosis also develops in immune-suppressed heart transplant patients infected with CMV. The properties of CMV are consistent with its involvement at several levels of the atherogenic process. If this concept is correct, immunization with a CMV vaccine should prevent CMV infection and atherosclerosis.

To date, men exposed to DES in utero do not appear to have an increased risk of most cancers. It remains uncertain, however, whether prenatal DES exposure is associated with testicular cancer.