Vascular dysfunction in young, mid-aged and aged mice with latent cytomegalovirus infections

Abstract

Gombos RB, Brown JC, Teefy J, Gibeault RL, Conn KL, Schang LM, Hemmings DG. Vascular dysfunction in young ec50, mid-aged and aged mice with latent cytomegalovirus infections. Am J Physiol Heart Circ Physiol 304: H183-H194, 2013. First published November 2, 2012; doi:10.1152/ajpheart.00461.2012.-Human cytomegalovirus (HCMV) is associated with vascular diseases in both immunosuppressed and immunocompetent individuals. CMV infections cycle between active and latent phases throughout life. We and others have shown vascular dysfunction during active mouse CMV (mCMV) infections. Few studies have examined changes in physiology during latent CMV infections, particularly vascular responses or whether the negative effects of aging on vascular function and fertility will be exacerbated under these conditions. We measured vascular responses in intact mesenteric and uterine arteries dissected from young, mid-aged, and aged latently mCMV-infected (mCMV genomes are present but infectious virus is undetectable) and agematched uninfected mice using a pressure myograph. We tested responses to the ␣ 1-adrenergic agonist phenylephrine, the nitric oxide donor sodium nitroprusside, and the endothelium-dependent vasodilator methacholine. In young latently mCMV-infected mice, vasoconstriction was increased and vasodilation was decreased in mesenteric arteries, whereas both vasoconstriction and vasodilation were increased in uterine arteries compared with those in age-matched uninfected mice. In reproductively active mid-aged latently infected mice, mesenteric arteries showed little change, whereas uterine arteries showed greatly increased vasoconstriction. These vascular effects may have contributed to the decreased reproductive success observed in mid-aged latently mCMV-infected compared with age-matched uninfected mice (16.7 vs. 46.7%, respectively). In aged latently infected mice, vasodilation is increased in mesenteric and uterine arteries likely to compensate for increased vasoconstriction to mediators other than phenylephrine. The novel results of this study show that even when active mCMV infections become undetectable, vascular dysfunction continues and differs with age and artery origin. uterine arteries; mesenteric arteries; infertility; vascular function; pressure myograph HUMAN CYTOMEGALOVIRUS (HCMV) is a member of the ␤-Herpesviridae family (50). In the human population, it infects 40 to 80% of individuals (10). Although in the general population it is thought to be mostly asymptomatic, infection has been associated with tumorigenesis, transplant rejection, vascular diseases such as atherosclerosis and restenosis, and increased mortality and hypertension (9,19,23,26,33,62,64). The mechanisms whereby HCMV infections result in vasculopathy are still unclear.

Human cytomegalovirus infection of human adipose-derived stromal/stem cells restricts differentiation along the adipogenic lineage

“…These diseases have also been linked to HCMV infection. 20,21,51 In summary, our data indicate that ASCs are highly susceptible to HCMV infection and support its replication leading to release of infectious HCMV progeny. Furthermore, HCMV infection inhibits adipogenic differentiation and immunomodulatory function of ASCs.…”

“…18 Long thought of as nonproblematic, HCMV latency is now being investigated for a possible role in chronic conditions including metabolic syndrome, cardiovascular disease, diabetes, cognitive impairment, and immunosenescence. [18][19][20][21] Recent studies show that HCMV infects progenitor cells of various types resulting in alterations in their phenotype and function. [22][23][24] The goal of this study was to determine if ASCs are susceptible and permissive for productive infection by HCMV, and if so, the consequences in terms of differentiation potential and anti-inflammatory properties.…”

Productive Cytomegalovirus Infection Is Associated With Impaired Endothelial Function in ST-Elevation Myocardial Infarction

“…Moreover, in experimental studies it was found that cytomegalovirus infection can induce severe endothelial dysfunction 50,51 and altered response to oxidized lipids in the subendothelium, 52 leading to atherosclerosis progression. However, the transition from experimental settings to clinical studies resulted in a contradiction.…”

Vascular Dysfunction in Ocular Blood Flow Regulation: Impact of Reactive Oxygen Species in an Experimental Setup

“…Similar setups are often used in studies on vascular physiology. 19,20 The experimental setup is schematically drawn in Figure 1.…”