Fluid Shear Stress Induces Lipocalin-Type Prostaglandin D ₂ Synthase Expression in Vascular Endothelial Cells

Abstract

Ligands for peroxisome proliferator-activated receptor gamma, such as the thiazolidinedione class of antidiabetic drugs and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), modulate various processes in atherogenesis. In search of cells that generate prostaglandin D(2) (PGD(2)), the metabolic precursor of 15d-PGJ(2), we identified PGD(2) from culture medium of endothelial cells. To study how PGD(2) production is regulated in endothelial cells, we investigated the role of fluid shear stress in the metabolism of PGD(2). Endothelial cells expressed the mRNA for the lipocalin-type PGD(2) synthase (L-PGDS) both in vitro and in vivo. Loading laminar shear stress using a parallel-plate flow chamber markedly enhanced the gene expression of L-PGDS, with the maximal effect being obtained at 15 to 30 dyne/cm(2). The expression began to increase within 6 hours after loading shear stress and reached the maximal level at 18 to 24 hours. In contrast, shear stress did not alter the expression levels of PGI(2) synthase and thromboxane A(2) synthase. In parallel with the increase in the expression level of L-PGDS, endothelial cells released PGD(2) and 15d-PGJ(2) into culture medium. These results demonstrate that shear stress promotes PGD(2) production by stimulating L-PGDS expression and suggest the possibility that a peroxisome proliferator-activated receptor gamma ligand is produced in vascular wall in response to blood flow.

β-Trace Protein

“…It is not surprising, therefore, that BTP levels are elevated in circulation of patients with severe coronary heart disease, and for that reason, recent studies have highlighted the implications of BTP in progression of several cardiovascular diseases (5,(12)(13)(14)(15)(16)(17). It is important to remark that prostaglandins derived from PGD 2 -and hence, extending from BTP-exert significant effects on the cardiovascular system, including 15-deoxy-D12,14-PGJ 2 (15d-PGJ 2 ), the most effective endogenous activator for the nuclear receptor peroxisome proliferator-activate receptor g (PPARg) (42). 15d-PGJ 2 promotes several processes in vascular cells, such as antiatherogenic, antithrombogenic, antiapoptotic, and antiinflammatory effects (42) (Figure 1).…”

Oxidative stress-inducible lentiviral vectors for gene therapy

“…17 15d-PGJ 2 is a lipid oxidation product derived from the cyclooxygenase pathway, and it has been shown to be produced during inflammation 22 and shear stress. 23,24 It is also a potent inducer of Nrf2. 17,19 In HUVECs, the reporter gene expression of all constructs was increased by 15d-PGJ 2 ( Figure 2c).…”

The lipocalin-type prostaglandin D2 synthase knockout mouse model of insulin resistance and obesity demonstrates early hypothalamic–pituitary–adrenal axis hyperactivity

“…It also plays a protective, anti-inflammatory role in some neurological disorders such as Alzheimer's disease (Kanekiyo et al 2007) and cerebral ischemia (Saleem et al 2009). In the periphery, it is found in the vascular endothelium (Taba et al 2000) as well as adipose tissue (Quinkler et al 2006, Fujimori et al 2007. Its role in the vasculature is thought to be a protective one, where its downstream prostaglandin (PGD 2 ) and its derivative 15d-PGJ 2 have anti-inflammatory properties (Sasaguri & Miwa 2004).…”