Estradiol Inhibits Certain Inflammatory Activation of C-Reactive Protein

Cardiovascular disease (CVD) is currently the most important cause of death in developed countries.

• Atherosclerosis, the underlying cause of most CVDs, is a dynamic and progressive inflammatory disease characterized by lipid plaque formation within the arterial wall and luminal reduction. In fact, accumulating


• Data suggests that the inflammatory process plays a central role in the initiation, progression, and the final steps of this pathology as vulnerable plaque rupture.


• The C-reactive protein (CRP) has emerged as the most powerful predictor and is an extensively studied systemic marker of inflammation of high sensitive CRP (hsCRP) correlates with the risk of future atherosclerotic events.


• This plasmatic protein synthesized by hepatocytes in response to inflammation and tissue injury induces pro-inflammatory molecules' expression by endothelial cells (ECs).


• [style=font-weight: bold;]Previous studies showed that the 17?-estradiol (E2) has beneficial effects on vascular cells by reducing in vitro pro-inflammatory molecules expressions in EC.[/style] [style=font-weight: bold;]It is hypothesized that E2 blocks or reduces CRP-mediated inflammatory responses by modulating endogenous production of CRP in EC and/or activation mechanisms.[/style]


• A 1-h pre-treatment of E2 at a physiologic dose (10[SUP][style=font-size: small;]?9[/style][/SUP]M) leads to an important decrease of CRP production suggesting a partial blockage of its amplification loop mechanism.


• Furthermore, in HAEC, E2 reduces the secretion of the most potent agonist of CRP induction, the IL-6, by 21 %. E2 pre-treatment also decreased the expression of pro-inflammatory molecules IL-8, VCAM-1, and ICAM-1 induced by CRP and involved in leukocytes recruitment.


• In addition, we demonstrated that E2 could restore vascular endothelial growth factor-mediated EC migration response impaired by CRP suggesting another pro-angiogenic property of this hormone.

"Effect of C-reactive protein on chemokine expression in human aortic endothelial cells," [style=font-style: italic;]Journal of Molecular and Cellular Cardiology,[/style]2004 March, https://www.ncbi.nlm.nih.gov/pubmed/23111890