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TORONTO, May 14 -- A common virus may lead to high blood pressure and -- in combination with other risk factors -- atherosclerosis, U.S. researchers said.
At least in mice, infection with cytomegalovirus was associated with increases in arterial blood pressure within a few weeks regardless of diet, according to Clyde Crumpacker, M.D., of Beth Israel Deaconess Medical Center in Boston, and colleagues.
When the animals were also fed a high-fat diet, the hypertension was accompanied by signs of atherosclerosis in about 30%, they reported in the May 15 issue of PLoS Pathogens.
The virus "infects humans all over the world," Dr. Crumpacker said in a statement, with estimates of global prevalence ranging from 60% to 99% of adults.
"This new discovery," Dr. Crumpacker said, "may eventually provide doctors with a whole new approach to treating hypertension, with antiviral therapies or vaccines becoming part of the prescription."
Epidemiological evidence had linked cytomegalovirus with restenosis in cardiac transplant patients and with the development of atherosclerosis, but the mechanism was unknown.
To clarify the issue, Dr. Crumpacker and colleagues conducted a series of animal and laboratory experiments, including a trial in 48 mice, divided into four groups.
Mice in two groups were fed a normal diet, but one set was infected with the mouse version of cytomegalovirus.
Mice in the other two groups were fed a high-fat diet and, again, one group was infected with the virus.
The researchers measured carotid artery pressure after six weeks of infection, using a microtip catheter, and found significant increases in systolic and diastolic pressure in both infected groups, compared with the uninfected animals.
For instance, among the animals fed a normal diet, the average systolic blood pressure was about 80 mm Hg for the infected animals, compared with about 70 for the control group. The difference was significant at P<0.01.
The difference was also significant (at P<0.05) for the animals on the high-fat diet, the researchers said.
Neither virus infection nor high-fat diet alone caused atherosclerosis during the study period, the researchers noted, suggesting that atherosclerosis seen in infected mice fed a high-fat diet was the result of a combination of effects.
In blood from infected mice, the researchers found, the virus was associated with increased production of three inflammatory cytokines -- interleukin-6, tumor necrosis factor-alpha, and monocyte chemotactic protein-1.
The differences from uninfected animals were significant at P<0.001, P<0.001, and P<0.01, respectively.
The implication, the researchers said, is that the virus was causing inflammation of vascular cells and other tissues.
In a second experiment, infection of a mouse kidney cell line with the virus led to an increase in expression of renin, an enzyme that can activate the renin-angiotensin system and lead to high blood pressure.
Finally, the researchers showed that the virus was associated with increased expression of the protein angiotensin II, which is also part of the rennin-angiotensin system.
"Increased expression of both renin and angiotensin II are important factors in hypertension in humans," Dr. Crumpacker said. "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 II, which are leading to increased blood pressure."
The study was supported by the National Heart, Lung and Blood Institute. The researchers reported no conflicts.
At least in mice, infection with cytomegalovirus was associated with increases in arterial blood pressure within a few weeks regardless of diet, according to Clyde Crumpacker, M.D., of Beth Israel Deaconess Medical Center in Boston, and colleagues.
When the animals were also fed a high-fat diet, the hypertension was accompanied by signs of atherosclerosis in about 30%, they reported in the May 15 issue of PLoS Pathogens.
The virus "infects humans all over the world," Dr. Crumpacker said in a statement, with estimates of global prevalence ranging from 60% to 99% of adults.
"This new discovery," Dr. Crumpacker said, "may eventually provide doctors with a whole new approach to treating hypertension, with antiviral therapies or vaccines becoming part of the prescription."
Epidemiological evidence had linked cytomegalovirus with restenosis in cardiac transplant patients and with the development of atherosclerosis, but the mechanism was unknown.
To clarify the issue, Dr. Crumpacker and colleagues conducted a series of animal and laboratory experiments, including a trial in 48 mice, divided into four groups.
Mice in two groups were fed a normal diet, but one set was infected with the mouse version of cytomegalovirus.
Mice in the other two groups were fed a high-fat diet and, again, one group was infected with the virus.
The researchers measured carotid artery pressure after six weeks of infection, using a microtip catheter, and found significant increases in systolic and diastolic pressure in both infected groups, compared with the uninfected animals.
For instance, among the animals fed a normal diet, the average systolic blood pressure was about 80 mm Hg for the infected animals, compared with about 70 for the control group. The difference was significant at P<0.01.
The difference was also significant (at P<0.05) for the animals on the high-fat diet, the researchers said.
Neither virus infection nor high-fat diet alone caused atherosclerosis during the study period, the researchers noted, suggesting that atherosclerosis seen in infected mice fed a high-fat diet was the result of a combination of effects.
In blood from infected mice, the researchers found, the virus was associated with increased production of three inflammatory cytokines -- interleukin-6, tumor necrosis factor-alpha, and monocyte chemotactic protein-1.
The differences from uninfected animals were significant at P<0.001, P<0.001, and P<0.01, respectively.
The implication, the researchers said, is that the virus was causing inflammation of vascular cells and other tissues.
In a second experiment, infection of a mouse kidney cell line with the virus led to an increase in expression of renin, an enzyme that can activate the renin-angiotensin system and lead to high blood pressure.
Finally, the researchers showed that the virus was associated with increased expression of the protein angiotensin II, which is also part of the rennin-angiotensin system.
"Increased expression of both renin and angiotensin II are important factors in hypertension in humans," Dr. Crumpacker said. "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 II, which are leading to increased blood pressure."
The study was supported by the National Heart, Lung and Blood Institute. The researchers reported no conflicts.