25-Hydroxycholesterol Increases Eicosanoids and Alters Morphology in Cultured Pulmonary Artery Smooth Muscle and Endothelial Cells

Abstract

Abstract-25-Hydroxycholesterol (25-OHC) is an oxidized derivative of cholesterol that has been implicated in the early development of arteriosclerosis. Changes in arterial smooth muscle cell (SMC) migration and proliferation have also been linked to the pathophysiology of arteriosclerosis. SMCs undergo "activation" in response to vascular injury by changing phenotypically and by increasing prostaglandin G/H synthase-2 (PGHS-2) protein levels and eicosanoid release. Activation is thought to be important in atheroma formation and arteriosclerosis progression. 25-OHC induces SMCs to change morphologically, increase PGHS-2, and increase eicosanoid release. Confluent monolayers were treated with 25-OHC (10 g/mL) or the PGHS-2 inducer interleukin-1␤ (1 ng/mL) for 18 hours at 37°C. The 18-hour treatment resulted in morphological changes. After uptake of [ 14 C]arachidonic acid, released radiolabeled arachidonic acid products were extracted and chromatographed by both normal and reverse-phase high-performance liquid chromatography systems. 25-OHC-treated cells increased their prostaglandin production, with the major component comigrating with a prostaglandin-E 2 standard. HETEs and epoxyeicosatrienoic acids were not affected. Immunoprecipitation analysis of treated and control cell lysates using anti-PGHS-1 and -2 and anti-␣-actin primary antibodies indicated PGHS-2 induction over control and no change in contractile proteins. These changes are consistent with SMC activation, which occurs in vascular injury models. The notion that oxysterols can activate vascular SMCs may be important in ultimately understanding the pathophysiology of atheroma formation. (Arterioscler Thromb Vasc Biol. 1999;19

Notch3 and IL-1β exert opposing effects on a vascular smooth muscle cell inflammatory pathway in which NF-κB drives crosstalk

“…1C,D). DAPT also enhances the secretion of PGE 2 , the principal prostanoid released during inflammation (Wen et al, 1998;Wohlfeil and Campbell, 1999;Yamamoto et al, 1999), after 24 and 48 hours of IL-1␤ treatment (Fig. 1E).…”

Human Vascular Smooth Muscle Cells but Not Endothelial Cells Express Prostaglandin E Synthase

“…Our results are also consistent with previous reports that PGE 2 is the most commonly induced prostanoid by IL-1␤ in SMCs, although in these works PGES expression was not analyzed. 21,22 Matsumoto et al 23 observed that LPS induced COX-2 expression and enhanced PGES activity in rat macrophages. The fact that not only PGE 2 but also PGI 2 was increased by PMA, IL-1␤, and TNF-␣ in SMCs was due to the induction of COX-2 (evaluated by RT-PCR and Western blotting [not shown]) by these agents, which indicates that formation of PGI 2 in SMCs is limited by COX activity rather than by PGIS.…”

Omega–3 Fatty Acids, Inflammation and Angiogenesis: Nutrigenomic Effects as an Explanation for Anti-Atherogenic and Anti-Inflammatory Effects of Fish and Fish Oils

“…COX-2 directly contributes to plaque instability, favoring the MMP release in macrophages, as observed in vitro [48] and in vivo in atherosclerotic lesions obtained from patients with symptomatic carotid artery disease, where the simultaneous overexpression of functionally coupled COX-2, PGE synthase and MMP has been reported [49] . Secondly, prostaglandins exert potent actions on vascular SMC, regulating contractility [50,51] , cholesterol metabolism [52] , and proliferation [53] . The increased expression of COX-2 may thus contribute to the accumulation of lipids in lesional SMC, besides macrophages, favoring the formation of SMC and macrophage-derived foam cells within the atheroma.…”