Hypertension, an infectious disease!!??

Cytomegalovirus Infection Causes an Increase of Arterial Blood Pressure
PLoS Pathog. 2009 May.

Jilin Cheng1, Qingen Ke, Zhuang Jin, Haibin Wang, Olivier Kocher, James P. Morgan, Jielin Zhang1, Clyde S. Crumpacker

Free full text: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000427

The debate on the role played by chronic CMV infection in the pathogenesis of atheroschlerosis and associated cardiovascular diseases is not new. While some studies have supported this association (Grahame-Clarke C et al., 2003, Valantine et al., 1999, Hsich et al., 2001), others have not (Zhou et al., 1996, Adler et al, 1998, Saetta et al., 2000, Stassen et al., 2006).

In this paper, this group of authors from Harvard Medical School has shown, using in vitro and in vivo methods, that CMV infection increases arterial blood pressure and accelerates atheroschlerosis in mice fed with a high cholesterol diet. The authors say, “CMV infection alone causes an increase in blood pressure. CMV infection augments the increased blood pressure induced by a high cholesterol diet. CMV infection alone, however, does not cause atherosclerosis in aortas. CMV infection along with a high cholesterol diet, however, causes the classic atherosclerotic plaque formation in the main artery connected to the heart. Further studies show that CMV infection induces renin and angiotensin II (Ang II) expression in blood and in vessel cells, in a persistent infection manner. An increased expression of renin and Ang II has been known to cause an increase in blood pressure or hypertension in humans. Expression of viral genes and viral persistent infection of blood vessel endothelial cells resulting in an increased expression of inflammatory cytokines, including renin and Ang II, may underpin the molecular mechanism by which CMV infection induces an increase in blood pressure. Therefore, non-lytic CMV infection and the perturbed cellular gene expression, specifically the components of RAS, underlie a molecular mechanism by which CMV infection causes an increase of blood pressure”.

The significance of these findings lies in the fact that CMV infection is very prevalent all over the world. Several studies have shown that the prevalence of chronic CMV infection in the general population to vary between 60 to 99%. Hypertension and cardiovascular diseases are also very common in the general population. If CMV infection is proved to play an important role, either in the initiation of atheroschlerosis or in its evolution, control of CMV infection (using drugs or vaccines) may provide a new strategy to prevent cardiovascular diseases in the population.

References:
Grahame-Clarke C, Chan NN, Andrew D, Ridgway GL, Betteridge DJ, et al. (2003) Human cytomegalovirus seropositivity is associated with impaired vascular function. Circulation 108: 678–683

Valantine HA, Gao SZ, Menon SG, Renlund DG, Hunt SA, et al. (1999) Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: a post hoc analysis of a randomized, placebo-controlled study. Circulation 100: 61–66.

Hsich E, Zhou YF, Paigen B, Johnson TM, Burnett MS, et al. (2001) Cytomegalovirus infection increases development of atherosclerosis in Apolipoprotein-E knockout mice. Atheroslcerosis 156: 23–28.

Zhou YF, Leon MB, Waclawiw MA, Popma JJ, Yu ZX, et al. (1996) Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. N Engl J Med 335: 624–630.

Adler SP, Hur JK, Wang JB, Vetrovec GW (1998) Prior infection with cytomegalovirus is not a major risk factor for angiographically demonstrated coronary artery atherosclerosis. J Infect Dis 177: 209–212.

Saetta A, Fanourakis G, Agapitos E, Davaris PS (2000) Atherosclerosis of the carotid artery: absence of evidence for CMV involvement in atheroma formation. Cardiovasc Pathol 9: 181–183.

Stassen FR, Vega-Cordova X, Vliegen I, Bruggeman CA (2006) Immune activation following cytomegalovirus infection: more important than direct viral effects in cardiovascular disease? J Clin Virol 35: 349–353.