C-reactive protein: Risk marker or mediator in atherothrombosis?

Ishwarlal Jialal, Sridevi Devaraj, Senthil K. Venugopal

Research output: Contribution to journalArticle

460 Citations (Scopus)

Abstract

Inflammation appears to be pivotal in all phases of atherosclerosis from the fatty streak lesion to acute coronary syndromes. An important downstream marker of inflammation is C-reactive protein (CRP). Numerous studies have shown that CRP levels predict cardiovascular disease in apparently healthy individuals. This has resulted in a position statement recommending cutoff levels of CRP <1.0, 1.0 to 3.0, and >3.0 mg/L equating to low, average, and high risk for subsequent cardiovascular disease. More interestingly, much in vitro data have now emerged in support of a role for CRP in atherogenesis. To date, studies largely in endothelial cells, but also in monocyte-macrophages and vascular smooth muscle cells, support a role for CRP in atherogenesis. The proinflammatory, proatherogenic effects of CRP that have been documented in endothelial cells include the following: decreased nitric oxide and prostacyclin and increased endothelin-1, cell adhesion molecules, monocyte chemoattractant protein-1 and interleukin-8, and increased plasminogen activator inhibitor-1. In monocyte-macrophages, CRP induces tissue factor secretion, increases reactive oxygen species and proinflammatory cytokine release, promotes monocyte chemotaxis and adhesion, and increases oxidized low-density lipoprotein uptake. Also, CRP has been shown in vascular smooth muscle cells to increase inducible nitric oxide production, increase NFκB and mitogen-activated protein kinase activities, and, most importantly, upregulate angiotensin type-1 receptor resulting in increased reactive oxygen species and vascular smooth muscle cell proliferation. Future studies should be directed at delineating the molecular mechanisms for these important in vitro observations. Also, studies should be directed at confirming these findings in animal models and other systems as proof of concept. In conclusion, CRP is a risk marker for cardiovascular disease and, based on future studies, could emerge as a mediator in atherogenesis.

Original languageEnglish (US)
Pages (from-to)6-11
Number of pages6
JournalHypertension
Volume44
Issue number1
DOIs
StatePublished - Jul 2004

Fingerprint

C-Reactive Protein
Atherosclerosis
Vascular Smooth Muscle
Smooth Muscle Myocytes
Monocytes
Cardiovascular Diseases
Reactive Oxygen Species
Nitric Oxide
Endothelial Cells
Macrophages
Inflammation
Angiotensin Type 1 Receptor
Chemokine CCL2
Plasminogen Activator Inhibitor 1
Cell Adhesion Molecules
Thromboplastin
Endothelin-1
Epoprostenol
Chemotaxis
Acute Coronary Syndrome

Keywords

  • Atherosclerosis
  • Endothelium
  • Macrophages

ASJC Scopus subject areas

  • Internal Medicine

Cite this

C-reactive protein : Risk marker or mediator in atherothrombosis? / Jialal, Ishwarlal; Devaraj, Sridevi; Venugopal, Senthil K.

In: Hypertension, Vol. 44, No. 1, 07.2004, p. 6-11.

Research output: Contribution to journalArticle

Jialal, Ishwarlal ; Devaraj, Sridevi ; Venugopal, Senthil K. / C-reactive protein : Risk marker or mediator in atherothrombosis?. In: Hypertension. 2004 ; Vol. 44, No. 1. pp. 6-11.
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abstract = "Inflammation appears to be pivotal in all phases of atherosclerosis from the fatty streak lesion to acute coronary syndromes. An important downstream marker of inflammation is C-reactive protein (CRP). Numerous studies have shown that CRP levels predict cardiovascular disease in apparently healthy individuals. This has resulted in a position statement recommending cutoff levels of CRP <1.0, 1.0 to 3.0, and >3.0 mg/L equating to low, average, and high risk for subsequent cardiovascular disease. More interestingly, much in vitro data have now emerged in support of a role for CRP in atherogenesis. To date, studies largely in endothelial cells, but also in monocyte-macrophages and vascular smooth muscle cells, support a role for CRP in atherogenesis. The proinflammatory, proatherogenic effects of CRP that have been documented in endothelial cells include the following: decreased nitric oxide and prostacyclin and increased endothelin-1, cell adhesion molecules, monocyte chemoattractant protein-1 and interleukin-8, and increased plasminogen activator inhibitor-1. In monocyte-macrophages, CRP induces tissue factor secretion, increases reactive oxygen species and proinflammatory cytokine release, promotes monocyte chemotaxis and adhesion, and increases oxidized low-density lipoprotein uptake. Also, CRP has been shown in vascular smooth muscle cells to increase inducible nitric oxide production, increase NFκB and mitogen-activated protein kinase activities, and, most importantly, upregulate angiotensin type-1 receptor resulting in increased reactive oxygen species and vascular smooth muscle cell proliferation. Future studies should be directed at delineating the molecular mechanisms for these important in vitro observations. Also, studies should be directed at confirming these findings in animal models and other systems as proof of concept. In conclusion, CRP is a risk marker for cardiovascular disease and, based on future studies, could emerge as a mediator in atherogenesis.",
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