Acute Systemic Inflammation Impairs Endothelium-Dependent Dilatation in Humans

Hingorani, Aroon D.; Cross, Jenny; Kharbanda, Rajesh K.; Mullen, Michael; Bhagat, K; Taylor, M.; Donald, Ann; Palacios, Miriam; Griffin, George E.; Deanfield, John; MacAllister, Raymond J.; Vallance, Patrick

doi:10.1161/01.cir.102.9.994

Cited by 544 publications

(432 citation statements)

References 34 publications

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“…23,24 Inflammation is associated with endothelial dysfunction, which may lead to functional stiffening of the large arteries due to reduced nitric oxide bioavailability and increased activity of opposing mediators such as endothelin-1. 25,26 Endothelial dysfunction may lead to a number of changes in the extracellular matrix including smooth muscle cell proliferation and increased synthesis of structural proteins including collagen as well. 27 Moreover, an increase in circulating inflammatory mediators directly promotes white cell infiltration into arteries, and a change in vascular smooth muscle phenotype.…”

Section: Discussionmentioning

confidence: 99%

C-reactive protein and aortic stiffness and wave reflection in middle-aged and elderly men from the community

et al. 2007

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High plasma C-reactive protein (hs-CRP) levels and arterial stiffness are risk factors for cardiovascular diseases. Pulse wave velocity (PWV) and augmentation index (AIx) have been found to be elevated in patients with vascular inflammation, diabetes mellitus, hypertension, hypercholesterolemia and in smokers. We investigated the relation of high-sensitivity CRP (hs-CRP) with aortic stiffness in 362 men. The levels of hs-CRP were measured using a nephelometric method. Aortic PWV and AIx were assessed from carotid-femoral segment and radial artery waveforms with the use of the SphygmoCor device. In the crude model, aortic PWV increased significantly with increasing serum hs-CRP levels; PWV increased by 2.48 m/s (95% CI 1.58; 3.38) in the fifth compared to the first quintile of hs-CRP. In the adjusted model, the PWV increased by 0.84 m/s (95% CI 0.13; 1.55) in the fifth quintile compared to the first quintile (P-value was 0.02). In the crude model, AIx increased significantly with increasing serum hs-CRP levels; AIx increased by 7.17% (95% CI 3.72; 10.62) in the fifth versus the first quintile. Adjusted for confounders, AIx remained 4.57% (95% CI 1.32; 7.82) higher in the fifth compared to the first quintile (P-value for trend was o0.01). More adjustment for subclinical atherosclerosis attenuated the b-coefficient for PWV (difference 0.71 m/s (95% CI 0.01; 1.41), but not for AIx (4.60% (95% CI 1.34; 7.85)). In summary, low-grade inflammation seems to be independently related to increase of aortic artery stiffness over and above traditional risk factors and atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

C-reactive protein and aortic stiffness and wave reflection in middle-aged and elderly men from the community

et al. 2007

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“…This mechanism might be mediated by cytokines such as interleukin-6 [26] and tumor necrosis factor α [27,28]. Our recent experimental studies have shown a profound and diffuse impairment of endothelial function of coronary vascular bed during acute C. pneumoniae infection in piglets [23].…”

Section: Mechanism Of Infection Initiated Chdmentioning

confidence: 99%

Dual role of infections as risk factors for coronary heart disease

et al. 2007

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“…Hingorani et al (2000) made measurements of vascular function immediately before and after Salmonella typhi vaccination, which produces an acute inflammatory response and increased circulating levels of inflammatory cytokines. Vaccination was associated with short-term impairment of endothelium-dependent dilation in conduit and resistance vessels that paralleled the inflammatory response.…”

Section: Human Studies Of Systemic Inflammation and Endothelial Dysfumentioning

confidence: 99%

Effects of Systemic Inflammation on Endothelium-Dependent Vasodilation

Huang

Vita

2006

Trends in Cardiovascular Medicine

110

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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 ...

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Acute Systemic Inflammation Impairs Endothelium-Dependent Dilatation in Humans

Cited by 544 publications

References 34 publications

C-reactive protein and aortic stiffness and wave reflection in middle-aged and elderly men from the community

C-reactive protein and aortic stiffness and wave reflection in middle-aged and elderly men from the community

Dual role of infections as risk factors for coronary heart disease

Effects of Systemic Inflammation on Endothelium-Dependent Vasodilation

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