&lt;EMPH TYPE="ITAL"&gt;Chlamydia pneumoniae&lt;/EMPH&gt; and Atherosclerosis

Shor, Allan; Phillips, James I.

doi:10.1001/jama.282.21.2071

Cited by 51 publications

(43 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Atherosclerotic lesions may be the result of some form of inflammation induced by the presence of oxidized LDL, Chlamydia pneumoniae, 32 or viral or other factors occurring at the level of the vessel wall. 33 Vascular endothelial cells, activated at sites of inflammation, interact with different leukocyte subtypes through adhesion molecules and various cofactors and are thought to play a key role in the initiation and perpetuation of atherosclerotic lesions.…”

Section: Discussionmentioning

confidence: 99%

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE ⁻ ^/− /ICAM-1 ⁻ ^/− ) Fed a Fat or a Chow Diet

Bourdillon

Poston

Covacho

et al. 2000

ATVB

147

View full text Add to dashboard Cite

Abstract-Intercellular adhesion molecule (ICAM)-1, a major adhesion molecule, plays a critical role in the homing of leukocytes to sites of atherosclerotic lesions. However, very little is known on the role of ICAM-1 in initiating and perpetuating vascular lesions in ApoE Ϫ/Ϫ mice fed a chow or a fat diet. This study has investigated the mean aortic lesions in mice (C57BL6 background) with a single-knockout (ApoE Ϫ/Ϫ ) or double-knockout (DKO; ApoE Ϫ/Ϫ , ICAM-1 Ϫ/Ϫ ) fed a chow or a fat diet over a period of 3, 6, 15, and 20 weeks. A 3-fold reduction in lesion size was observed at all time points in DKO mice fed a chow diet. However, in DKO mice fed a fat diet, a marked reduction in the aortic lesion was observed at 3 and 15 weeks, which did not reach a significant level at 6 and 20 weeks. This study shows in essence that DKO mice are protected from developing significant lesions for up to 6 weeks when fed a chow diet and from 3 to 6 weeks when fed a fat diet. After 6 weeks, the lesion size of the DKO mice follows that of the single-knockout mice when fed a chow diet and gets to the same level in mice fed a fat diet. Plasma cholesterol levels were not altered as a result of ICAM-1 deficiency. These studies show that ICAM-1 is implicated in the formation and progression of atherosclerotic lesions.

show abstract

Section: Discussionmentioning

confidence: 99%

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE ⁻ ^/− /ICAM-1 ⁻ ^/− ) Fed a Fat or a Chow Diet

Bourdillon

Poston

Covacho

et al. 2000

ATVB

147

View full text Add to dashboard Cite

show abstract

“…43,44 Overall, the evidence in animal and human studies has been inconclusive. 45 Furthermore, in 1 coronary artery disease trial of 302 patients treated with azithromycin for 3 months, global tests of inflammatory markers improved at 6 months, but there were no differences in antibody titers or clinical outcome events. 46 Therefore, uncertainty exists in this area regarding what types of infection should be treated, which patients might be appropriate for treatment, and how long patients should be treated.…”

Section: Recent Infectionmentioning

confidence: 94%

Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy

Gorelick

2002

Stroke

196

115

View full text Add to dashboard Cite

Background — It is estimated that about half of cardiovascular disease risk is explained by conventional risk factors. The realization that atherosclerosis is an inflammatory disease has led to a search for new stroke and cardiovascular disease risk factors and treatments. As such, the vulnerable atherosclerotic plaque has become the main focus for new medical strategies for plaque stabilization and stroke prevention. Summary of Review — In this invited review, I discuss inflammation as a possible risk factor for stroke, unifying mechanisms in ischemic stroke pathogenesis, and new avenues for stroke prevention—statin agents, angiotensin-converting enzyme inhibitors, and vitamins. These new stroke prevention therapies may help to reduce inflammation, serve to stabilize the atherosclerotic plaque, or act by other protective mechanisms. Conclusion — Beyond the traditional antithrombotic agents, statin agents, angiotensin-converting enzyme inhibitors, and vitamins may prove to be important additions to our armamentarium for stroke prevention.

show abstract

“…Cells were rapidly frozen in liquid nitrogen and then harvested in buffer containing (in mmol/L) NaCl 150, HEPES (pH 7.4) 50, NaVO 4 1, and NaF 1; 1% Triton X-100; 10% glycerol; and proteinase inhibitor cocktail (Boehringer Mannheim). Cell lysates were gently rotated (15 minutes, 4°C), centrifuged (16 000g, 20 minutes, 4°C), and the supernatants stored at Ϫ80°C.…”

Section: P44/p42 Mapk Phosphorylationmentioning

confidence: 99%

“…The first report linking C pneumoniae to atherosclerosis identified the organism by electron microscopy in coronary atherosclerotic plaques and localized it to intimal smooth muscle cells (SMCs). 2 C pneumoniae has been found frequently in lesions of the aorta, iliac, carotid, and coronary arteries, [3][4][5] but is rarely found in normal arterial tissue. 6 In vitro evidence supports the notion that C pneumoniae can infect human arterial SMCs.…”

mentioning

confidence: 99%

Chlamydia pneumoniae and Chlamydial Heat Shock Protein 60 Stimulate Proliferation of Human Vascular Smooth Muscle Cells via Toll-Like Receptor 4 and p44/p42 Mitogen-Activated Protein Kinase Activation

Sasu

LaVerda

Qureshi

et al. 2001

Circulation Research

262

214

View full text Add to dashboard Cite

Abstract-An early component of atherogenesis is abnormal vascular smooth muscle cell (VSMC) proliferation. The presence of Chlamydia pneumoniae in many atherosclerotic lesions raises the possibility that this organism plays a causal role in atherogenesis. In this study, C pneumoniae elementary bodies (EBs) rapidly activated p44/p42 mitogen-activated protein kinases (MAPKs) and stimulated proliferation of VSMCs in vitro. Exposure of VSMCs derived from human saphenous vein to C pneumoniae EBs (3ϫ10 7 inclusion forming units/mL) enhanced bromodeoxyuridine (BrdU) incorporation 12Ϯ3-fold. UV-and heat-inactivated C pneumoniae EBs also stimulated VSMC proliferation, indicating a role of direct stimulation by chlamydial antigens. However, the mitogenic activity of C pneumoniae was heat-labile, thus excluding a role of lipopolysaccharide. Chlamydial hsp60 (25 g/mL) replicated the effect of C pneumoniae, stimulating BrdU incorporation 7Ϯ3-fold. Exposure to C pneumoniae or chlamydial hsp60 rapidly activated p44/p42 MAPK, within 5 to 10 minutes of exposure. In addition, PD98059 and U0126, which are two distinct inhibitors of upstream MAPK kinase 1/2 (MEK1/2), abolished the mitogenic effect of C pneumoniae and chlamydial hsp60. Toll-like receptors (TLRs) act as sensors for microbial antigens and can signal via the p44/p42 MAPK pathway. Human VSMCs were shown to express TLR4 mRNA and protein, and a TLR4 antagonist abolished chlamydial hsp60 -induced VSMC proliferation and attenuated C pneumoniae-induced MAPK activation and VSMC proliferation. Together these results indicate that C pneumoniae and chlamydial hsp60 are potent inducers of human VSMC proliferation and that these effects are mediated, at least in part, by rapid TLR4-mediated activation of p44/p42 MAPK. A therosclerosis is an inflammatory disease, with the earliest stages characterized by the invasion of the intima by mononuclear phagocytes and by intimal hyperplasia. 1 Accumulating evidence indicates that chronic infection with the ubiquitous respiratory pathogen Chlamydia pneumoniae, a Gram-negative obligate intracellular bacterium, may be an additional risk factor for atherosclerosis. Macrophages are thought to become infected with C pneumoniae in the respiratory tract and then enter the circulation and cross the endothelium at sites of preexisting vascular inflammation. The first report linking C pneumoniae to atherosclerosis identified the organism by electron microscopy in coronary atherosclerotic plaques and localized it to intimal smooth muscle cells (SMCs). 2 C pneumoniae has been found frequently in lesions of the aorta, iliac, carotid, and coronary arteries, 3-5 but is rarely found in normal arterial tissue. 6 In vitro evidence supports the notion that C pneumoniae can infect human arterial SMCs. 7-9 However, it is not clear whether C pneumoniae organisms that have been identified within SMCs of human atheromas are actively replicating or viable. Irrespective of whether C pneumoniae replicates within SMCs in vivo, its presence in atherosclerotic lesions r...

show abstract

<EMPH TYPE="ITAL">Chlamydia pneumoniae</EMPH> and Atherosclerosis

Cited by 51 publications

References 36 publications

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE ⁻ ^/− /ICAM-1 ⁻ ^/− ) Fed a Fat or a Chow Diet

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE ⁻ ^/− /ICAM-1 ⁻ ^/− ) Fed a Fat or a Chow Diet

Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy

Chlamydia pneumoniae and Chlamydial Heat Shock Protein 60 Stimulate Proliferation of Human Vascular Smooth Muscle Cells via Toll-Like Receptor 4 and p44/p42 Mitogen-Activated Protein Kinase Activation

Contact Info

Product

Resources

About

<EMPH TYPE="ITAL">Chlamydia pneumoniae</EMPH> and Atherosclerosis

Cited by 51 publications

References 36 publications

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE − /− /ICAM-1 − /− ) Fed a Fat or a Chow Diet

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE − /− /ICAM-1 − /− ) Fed a Fat or a Chow Diet

Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy

Chlamydia pneumoniae and Chlamydial Heat Shock Protein 60 Stimulate Proliferation of Human Vascular Smooth Muscle Cells via Toll-Like Receptor 4 and p44/p42 Mitogen-Activated Protein Kinase Activation

Contact Info

Product

Resources

About

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE ⁻ ^/− /ICAM-1 ⁻ ^/− ) Fed a Fat or a Chow Diet

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE ⁻ ^/− /ICAM-1 ⁻ ^/− ) Fed a Fat or a Chow Diet