A common viral infection affecting between 60 and 99 percent of adults worldwide could be a cause of high blood pressure, according to the results of a mouse study.
One in three U.S. adults has high blood pressure, and because there are no known symptoms, nearly one-third of these individuals are unaware of their condition. Often dubbed “the silent killer,” uncontrolled high blood pressure can lead to stroke, heart attack, heart failure or kidney failure.
The researchers found that the viral infection alone led to an increase in high blood pressure, and when combined with a high cholesterol diet, the infection actually induced atherosclerosis (hardening of the arteries) in a mouse aorta.
A member of the herpes virus family, cytomegalovirus (CMV) affects all age groups and is the source of congenital infection, mononucleosis, and severe infection in transplant patients. By the age of 40, most adults will have contracted the virus, though many will never exhibit symptoms. Once it has entered the body, CMV is usually there to stay, remaining latent until the immune system is compromised, when it then reemerges.
In the first portion of the study, the scientists examined four groups of laboratory mice. Two groups of animals were fed a standard diet and two groups were fed a high cholesterol diet. After a period of four weeks, one standard diet mouse group and one high cholesterol diet mouse group were infected with the CMV virus.
Six weeks later, blood pressure was measured and among the mice fed a standard diet, the CMV-infected mice had increased blood pressure compared with the uninfected group. But even more dramatically, 30 percent of the CMV-infected mice that were fed a high cholesterol diet not only exhibited increased blood pressure, but also showed 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 study author Clyde Crumpacker. In order to find out how and why this was occurring, the investigators went on to conduct a series of cell culture experiments.
Their first analysis demonstrated that CMV stimulated production of three different inflammatory cytokines: IL6, TNF, and MCP1 in the infected mice, indication that the virus was causing inflammation to vascular cells and other tissues.
A second analysis found that 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. Clinical isolates of human CMV in cultured blood vessel cells also produced increased renin expression.
“Viruses have the ability to turn on human genes and, in this case, the CMV virus is enhancing expression of renin, an enzyme directly involved in causing high blood pressure,” says Crumpacker. When the scientists inactivated the virus through the use of ultraviolet light, renin expression did not increase, suggesting that actively replicating virus was causing the increase in renin.
In their final experiments, the researchers demonstrated that the protein angiotensin 11 was also increased in response to infection with CMV. “Increased expression of both renin and angiotensin 11 are important factors in hypertension in humans,” says 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.”
References:
1. Clyde Crumpacker, et al. Cytomegalovirus Infection Causes an Increase of Arterial Blood Pressure. PLoS Pathogens. doi:10.1371/journal.ppat.1000427.
