Estradiol inhibits vascular endothelial cells pro-inflammatory activation induced by C-reactive protein

Abstract

In addition of being an important inflammatory biomarker and a risk factor for cardiovascular disease, much evidence indicates that the C-reactive protein (CRP) contributes to the atherosclerosis development process. This plasmatic protein synthesized by hepatocytes in response to inflammation and tissue injury induces pro-inflammatory molecules' expression by endothelial cells (ECs). Previous studies showed that the 17β-estradiol (E2) has beneficial effects on vascular cells by reducing in vitro pro-inflammatory molecules expressions in EC. Therefore, we hypothesize that E2 blocks or reduces CRP-mediated inflammatory responses by modulating endogenous production of CRP in EC and/or activation mechanisms. Using human aortic ECs (HAECs), we first evaluated CRP production by vascular EC and second demonstrated its self-induction. Indeed, recombinant human CRP stimulation induces a fivefold increase of CRP expression. A 1-h pre-treatment of E2 at a physiologic dose (10−9 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. These findings suggest that E2 can interfere with CRP pro-inflammatory effects via activation signals using its rapid, non-genomic pathway that may provide a new mechanism to improve vascular repair.

Sex differences in the relationship of IL-6 signaling to cancer cachexia progression

“…Though the C26 and Apc Min/+ models of cancer cachexia are IL-6 dependent in the male (26, 29, 58), sex differences have been found in the C26 model of cachexia, providing evidence that this is not a singular phenomenon related to the Apc Min/+ mouse (9). Importantly, estrogen inhibits IL-6 transcription and signaling in many tissues (17, 18, 37-39); however, IL-6 is a known mediator of diseases in females including polycystic ovarian syndrome, ovarian cancer, and osteoporosis (38, 59, 60), indicating that females are susceptible to the pathophysiological effects of IL-6 under multiple circumstances regardless of estrogen status. The overall inflammatory environment related to the underlying disease may also alter IL-6 action.…”

“…Sex hormones can modulate the inflammatory response to a variety of stimuli (13-15). Specifically, estrogen is known to inhibit NfκB and tumor necrosis factor α (TNFα) signaling (13, 16), C-reactive protein (CRP)-induced interleukin-6 (IL-6) production (17), and signal transducer and activator of transcription-3 (STAT3) signaling downstream of IL-6 (18). In several rodent models of cachexia and some human cancers, IL-6 is associated with the development of muscle wasting and body weight loss (6, 8, 19-21).…”

“…Sex differences have been noted in the inflammatory milieu of humans (35, 36) and mice (14, 37) under multiple pathological circumstances. Additionally, estrogen has been shown to inhibit IL-6 transcription and signaling in several tissues (17, 18, 37-39), which may also lead to sex differences in IL-6 response during cancer cachexia progression. Therefore, the purpose of the present study was to examine the relationship of circulating IL-6 to cancer cachexia progression in the female Apc Min/+ mouse.…”

Effects of different surgical procedures on stress hormones, vascular inflammatory factors, tissue damage inflammatory factors in patients with renal calculi

“…PEG2, SP and BK are inflammatory factors that reflect vascular state: PEG2 as an important physiological active substance in organism can play a important role in regulating and controlling vangiogenesis [19,20]; SP as a vasoactive mediator can dilate blood vessels, improve permeability and cause inflammatory reactions such as edema [21]; BK as a Substance P9 peptide, may also dilate blood vessels, and is closely associated with inflammatory pain [22]. NO, AOPP and LPO are important indexes to tissue damage: NO can regulate the barrier function of vascular endothelial cells, when inflammatory tissue damages are observed, Induced Nitric-Oxide Synthase (INOS) in endothelial cells is activated and produces a large number of NO [23,24]; AOPP is a lipid peroxide produced by increased oxygen radical and decreased antioxidation, and peroxidation can lead to lesion in renal cell membrane [25,26]; LPO is also a lipid peroxide produced by the action of oxygen radical, can be aggregated to cell membrane and vessel wall, and then cause the lesions such as sclerosis and fibrous pathologic changes [27].…”

Pathomorphism of Limb Major Vessels in Experimental Atherogenic Inflammation. The Role of Adventitial Intimal Relations (Review)

“…Impaired expression balance of pro-atherogenic (proinflammatory) and anti-atherogenic (anti-inflammatory) cell markers if hyperlipidemia conditions are preserved stabilize destruction in subendothelial space. The expression of blood residual cell receptors under vascular endothelium and of vascular endothelium itself, namely: endothelin-1 [31][32][33][34][35], caveolins-1, -2, and -3 [36, 37], selectins Р (CD62P), Е (CD62E), L (CD62L), and antibodies to them on vascular endothelium, lymphocytes and platelets [38][39][40], intercellular adhesion molecule-1 (ICAM-1) marker [41][42][43], vascular cell adhesion molecule-1 (VCAM-1) marker [44][45][46][47], monocyte chemotactic protein (MCP-1) [48][49][50], macrophage colony-stimulating factor (MCSF) [51][52][53][54][55][56][57], pleiotropic cytokine (TNF-α) [58][59][60][61][62][63][64], С-reactive protein (CRP) [65][66][67][68][69][70], platelet derived growth factor (PDGF) [71][72][73][74][75][76][77], interleukin family in atherosclerosis <...>…”