Interleukin-1beta may act on hepatocytes to boost plasma homocysteine – The increased cardiovascular risk associated with elevated homocysteine may be mediated by this cytokine. (May 2017)

• Record Type: Journal Article
• Authors: McCarty, Mark F.; O'Keefe, James H.; DiNicolantonio, James J.
• Is Part Of: Medical hypotheses. Volume 102(2017)
• Page Start: 78
• Page End: 81
• Publication Date: 2017-05
• Subjects: CAD Coronary Artery Disease -- CBS cystathionine beta-synthase -- CRP C-reactive protein -- CV cardiovascular -- IL-1β interleukin-1beta -- IL-6 interleukin-6 -- LDL Low Density Lipoprotein -- SAM S-adenosylmethionine; Interleukin-1beta -- Cardiovascular -- C-reactive protein -- Interleukin-6 -- Low Density Lipoprotein -- Coronary Artery Disease -- Homocysteine -- Rosuvastatin; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Medicine; Periodicals; 610
• DOI: 10.1016/j.mehy.2017.03.022
• Languages: English
• ISSNs: 0306-9877

Abstract

Abstract: The results of multi-center trials of B vitamin supplementation reveal that, whereas moderately elevated homocysteine predicts increased risk for coronary disease, it does not play a mediating role in this regard. This essay proposes that interleukin-1beta can act on hepatocytes to suppress expression of the hepatocyte-specific forms of methionine adenosyltransferase; this in turn can be expected to decrease hepatic activity of cystathionine-β-synthase, leading to an increase in plasma homocysteine. It is further proposed that interleukin-1beta (IL-1β) is a true mediating risk factor for cardiovascular disease, and that elevated homocysteine predicts coronary disease because it can serve as a marker for increased IL-1β activity. Potent statin therapy may decrease IL-1β production by suppressing inflammasome activation – thereby accounting for the marked protection from cardiovascular events observed in the classic JUPITER study, in which the enrolled subjects had low-normal Low Density Lipoprotein cholesterol but elevated C-reactive protein.