Predisposition to Atherosclerosis by Infections

Prasad, Abhiram; Zhu, Jianhui; Halcox, Julian; Waclawiw, Myron A.; Epstein, Stephen E.; Quyyumi, Arshed A.

doi:10.1161/01.cir.0000021125.83697.21

Cited by 276 publications

(200 citation statements)

References 51 publications

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…Pathogen burden with many infectious agents has been reported to increase additionally the risk of cardiovascular events [32,33,34]. A recent study found a positive correlation between the number of pathogens in CHD patients undergoing angiography and the impairment of coronary artery reactivity to acetylcholine, an endothelium-dependent vasodilator [35]. Our study supports the pathogen burden hypothesis.…”

Section: Pathogen Burdensupporting

confidence: 88%

Dual role of infections as risk factors for coronary heart disease

et al. 2007

View full text Add to dashboard Cite

show abstract

Section: Pathogen Burdensupporting

confidence: 88%

Dual role of infections as risk factors for coronary heart disease

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In contrast, several larger studies have failed to observe a significant relationship between serum markers of inflammation and endothelium-dependent vasodilation. For example in a study of 218 patients undergoing coronary angiography, Prasad et al (2002) found no correlation between CRP and endothelium-dependent responses to acetylcholine in the coronary circulation. Similarly, Verma et al (2004) observed no correlation between CRP and brachial artery flow-mediated dilation in a group of 1154 healthy and relatively young male fire-fighters.…”

Section: Human Studies Of Systemic Inflammation and Endothelial Dysfumentioning

confidence: 98%

“…In addition, however, there has been considerable interest in the possibility that novel risk factors, including certain chronic infections, might also impair endothelial function and contribute to the development of atherosclerosis (Vallance et al 1997), for example, serologic evidence of prior infection with Chlamydia pneumoniae, cytomegalovirus, and other pathogens is associated with increased risk for cardiovascular disease (Epstein et al 2000). Interestingly, net infectious burden also correlates with the severity of endothelial dysfunction in patients with and without angiographically apparent coronary artery disease (CAD) (Prasad et al 2002). Chronic infections might alter endothelial function by stimulating a systemic inflammatory response or by directly invading endothelial cells and altering their function.…”

mentioning

confidence: 99%

Effects of Systemic Inflammation on Endothelium-Dependent Vasodilation

Huang

Vita

2006

Trends in Cardiovascular Medicine

118

View full text Add to dashboard Cite

The importance of inflammation in the pathogenesis of atherosclerosis is well established. The vascular endothelium contributes to and is affected by the inflammatory process. For example, a variety of cytokines have the ability to "activate" the endothelium and thereby promote expression of adhesion molecules and chemotactic factors that accelerate the inflammatory process and direct accumulation of leukocytes to specific sites in the arterial tree. In experimental systems, activation of endothelial cells is also associated with a loss of the biologic activity of endothelium-derived nitric oxide, an effect that accelerates the inflammatory process and also promotes local thrombosis and impairs local control of vasomotor tone. Consistent with these experimental studies, recent studies have provided evidence that inflammation is associated with an impairment of nitric oxide-dependent responses in human subjects. This article will review the experimental and clinical studies that support the relevance of inflammation to nitric oxide bioactivity in human atherosclerosis.It is now well recognized that atherosclerosis is an inflammatory disease (Ross 1999). Systemic risk factors induce a state of inflammation that contributes to all stages of atherosclerosis from the initiating events in lesion formation to the latest phase when plaques rupture, thrombose, and produce clinical syndromes such as myocardial infarction or stroke (Libby et al. 2002). The importance of inflammation in atherosclerosis is supported by recent studies showing that elevated levels of inflammatory markers identify individuals with increased risk for cardiovascular events (Pearson et al. 2003). In particular, the acute phase reactant C-reactive protein (CRP) shows promise as a clinically useful marker of cardiovascular risk (Ridker 2003).The vascular endothelium is both affected by and contributes to the inflammatory process that leads to atherosclerosis. For example, proinflammatory factors "activate" endothelial cells to promote an atherogenic phenotype. The activated endothelium, in turn, expresses adhesion molecules and chemotactic factors that accelerate and localize the inflammatory process. An important consequence of endothelial activation is loss of the biologic activity of endotheliumderived nitric oxide. Investigators have argued that a broad alteration of endothelial function, including loss of nitric oxide under proinflammatory conditions, might be a critical mechanism that links systemic states of inflammation to atherosclerosis (Vallance et al. 1997). This article will review the recent studies that support the relevance of systemic inflammation to nitric oxide bioactivity in human subjects. The Endothelium as a Regulator of Vascular HomeostasisThe endothelium regulates vasomotor tone, blood fluidity, growth of vascular smooth muscle cells, and local inflammation by elaborating a number of paracrine factors, including nitric oxide (Widlansky et al. 2003a). Endothelium-derived nitric oxide is a potent vasodilator and acts ...

show abstract

“…Studies have reported that patients with multiple past infections (high pathogen burden) demonstrate endothelial dysfunction, and that the 'pathogen burden' is an independent predictor of endothelial dysfunction (40). In a study by Prasad et al, the frequency of past infections with CMV and Hpyl were individually statistically significant predictors of CAD and endothelial dysfunction, even after adjusting for the conventional risk factors such as diabetes, cholesterol, hypertension and smoking (41). Endothelial dysfunction occurs as a consequence of a decrease in endotheliumderived nitric oxide that is required to maintain vascular homeostasis through its potent vasodilator functions and its anti-atherogenic effects.…”

Section: Infection and Endothelial Dysfunctionmentioning

confidence: 99%

The Role of Viruses in Cardiac Allograft Vasculopathy

Valantine

2004

American Journal of Transplantation

View full text Add to dashboard Cite

Considerable evidence suggests a role for viruses in transplant arteriosclerosis (TA), including observational data, experimental models and therapeutic trials implicating human cytomegalovirus (HCMV) in the progression to TA. In pediatric heart transplant patients, adenoviral genome in endomyocardial biopsies (EMB) is an important predictor of TA and graft loss. During CMV viremia, EMBs from adult patients demonstrate endothelialitis and vascular smooth muscle cell proliferation. These changes are predictors of subsequent diffuse TA. HCMV immediate early proteins (IE-1 and IE-2) increase the constitutive expression of intercellular adhesion molecule-1 (ICAM-1) independent of other intracellular cytokines. Likewise, viral chemokines such as US28 have been implicated in vascular disease because of their ability to induce smooth muscle cell migration. Recent data suggests that CMV might accelerate TA through its ability to abrogate the vascular protective effects of the endothelium-derived nitric oxide system (eNOS). Confirmation of causality requires clinical trials demonstrating that antiviral agents such as ganciclovir inhibit TA. Such studies in patients though limited to retrospective analyses, suggest that ganciclovir prophylaxis early after heart transplantation reduces the risk of TA. These observations emphasize the need for randomized controlled clinical trials to confirm a causal role for CMV (and other viruses) in TA.

show abstract

Predisposition to Atherosclerosis by Infections

Cited by 276 publications

References 51 publications

Dual role of infections as risk factors for coronary heart disease

Dual role of infections as risk factors for coronary heart disease

Effects of Systemic Inflammation on Endothelium-Dependent Vasodilation

The Role of Viruses in Cardiac Allograft Vasculopathy

Contact Info

Product

Resources

About