First study to link the common CMV virus to high blood pressure

By the age of 40, most people will have contracted the cytomegalovirus (CMV), a member of the herpes virus family that affects all age groups and causes congenital infection, mononucleosis and severe infection in transplant patients. It typically remains in a latent stage unless the immune system has been compromised, when it reemerges.  In past studies, CMV has been linked to a condition in cardiac transplant patients in which the heart's arteries "reblock." It had also been linked to the development of atherosclerosis, the hardening of the heart's arteries. However, in both of these cases, scientists have not understood the mechanism behind these developments.

Now, a new study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) has found that CMV can lead to hardening of the arteries when coupled with other risk factors for heart disease. To better understand how CMV might affect blood pressure, the researchers fed two groups of mice a standard diet and two groups a high cholesterol diet. After four weeks, they infected one of each group with the CMV virus. Six weeks later, the researchers measured the animals' blood pressure. They found that of those mice fed a standard diet, the CMV-infected mice had increased blood pressure compared with the uninfected group. But when examining the mice fed a high-cholesterol diet, they found even more dramatic results: 30 percent not only had increased blood pressure, but they also exhibited signs of having developed atherosclerosis. "This strongly suggests that the CMV infection and the high-cholesterol diet might be working together to cause atherosclerosis," says co-senior author Clyde Crumpacker, M.D., an investigator in the Division of Infectious Diseases at BIDMC and Professor of Medicine at Harvard Medical School.

The researchers also conducted a series of cell culture experiments, from which three findings emerged: CMV stimulated production of three different inflammatory cytokines in the infected mice, an indication that the virus was causing inflammation to vascular cells and other tissues; infection of a mouse kidney cell line with murine CMV led to an increase in expression of the renin enzyme, which has been known to activate the renin-angiotensin system and lead to high blood pressure; and the protein angiotensin 11 also increased in response to infection with CMV. "Increased expression of both renin and angiotensin 11 are important factors in hypertension in humans," says Dr. Crumpacker. "What our study seems to indicate is that a persistent viral infection in the vessels' endothelial cells is leading to increased expression of inflammatory cytokines, renin and angiotensin 11, which are leading to increased blood pressure."

The study brought together a team of researchers from a wide range of disciplines, including infectious diseases, cardiology, allergy and pathology. "By combining the insights of investigators from different medical disciplines, we were able to measure effects of a viral infection that may have been previously overlooked," explains Dr. Crumpacker. "This new discovery may eventually provide doctors with a whole new approach to treating hypertension, with anti-viral therapies or vaccines becoming part of the prescription." The findings were published in the May 15, 2009 issue of PLoS Pathogens.

News Release: High blood pressure could be caused by a common virus, study suggests  www.sciencedaily.com May 16, 2009