Neutrophil infiltration and systemic vascular inflammation in obese women.

Obesity has become epidemic worldwide and is especially pronounced in women of reproductive age, which is important because obesity is a major risk factor for preeclampsia and chronic hypertension. We hypothesized that vascular inflammation is critical to the pathophysiology of hypertension in obese individuals because obesity and hypertensive disorders share common features related to inflammation. To study this, we collected subcutaneous fat biopsies from normal weight, overweight, and obese women and stained the tissues for CD66b, a neutrophil marker, and for activated nuclear factor-kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) as markers of inflammation.

Systemic activation and vascular infiltration of neutrophils with term labor.

Objective: The purpose of the current study was to determine if neutrophils infiltrate maternal systemic vascular tissue at the time of term labor.

Methods: Subcutaneous fat biopsies were obtained at cesarean delivery or abdominal surgery from laboring women (n = 5), non-laboring women (n = 5), and normal non-pregnant women (n = 5). Immunohistochemical staining was performed for CD66b, a neutrophil antigen, and intercellular adhesion molecule-1 (ICAM-1; CD54), an endothelial cell adhesion molecule for neutrophils.

Modulation of adipose tissue development by pharmacological inhibition of PAI-1.

Objective: The effect of a novel small molecule plasminogen activator inhibitor (PAI-1) inhibitor on adipose tissue physiology was investigated.

Methods And Results: In human preadipocyte cultures, PAI-039 inhibited both basal and glucose-stimulated increases in active PAI-1 antigen, yet had no effect on PAI-1 mRNA, suggesting a direct inactivation of PAI-1. Differentiation of human preadipocytes to adipocytes was associated with leptin synthesis, which was significantly reduced in the presence of PAI-039, together with an atypical adipocyte morphology characterized by a reduction in the size and number of lipid containing vesicles.

Pharmacologic inhibition of platelet vWF-GPIb alpha interaction prevents coronary artery thrombosis.

Under high shear arterial blood flow von Willebrand Factor (vWF) binds the platelet receptor glycoprotein (GP) Ibalpha, leading to platelet adhesion, activation and thrombosis. Blockade of vWF-GPIb alpha interactions by GPG-290 was investigated in a canine model of coronary artery thrombosis alone and in combination with clopidogrel. GPG-290 (100 microg/kg, n=6; 500 microg/kg, n=6) prolonged time to thrombotic occlusion (TTO) to 105+/-34 and 156+/-23 (p<0.

Linoleic acid, but not oleic acid, upregulates production of interleukin-8 by human vascular smooth muscle cells via arachidonic acid metabolites under conditions of oxidative stress.

Objective: Preeclampsia is associated with oxidative stress, elevated plasma levels of linoleic acid (LA), and increased vascular smooth muscle expression of the inflammatory chemokine, interleukin-8 (IL-8). We hypothesized that increased levels of LA under conditions of oxidative stress would increased production of IL-8 by vascular smooth muscle cells because LA is the dietary precursor to arachidonic acid (AA) and its metabolites that mediate inflammation. We also hypothesized that oleic acid (OA), which is not metabolized to AA metabolites, would not increase IL-8 under conditions of oxidative stress.

Neutrophils infiltrate resistance-sized vessels of subcutaneous fat in women with preeclampsia.

We examined if there is systemic vascular inflammation and neutrophil infiltration in women with preeclampsia. Resistance-sized vessels (10 to 200 microm) of subcutaneous fat were evaluated from normal nonpregnant women, normal pregnant women, and preeclamptic women. Immunohistochemical staining was performed for: (1) interleukin-8 (IL-8), a potent neutrophil chemokine; (2) intercellular adhesion molecule-1 (ICAM-1; CD54), an endothelial cell adhesion molecule; and (3) CD66b, a neutrophil antigen.

Isolation and culture of arterial smooth muscle cells from human placenta.

A simple and economical technique was developed to isolate and culture human arterial smooth muscle cells from chorionic plate vessels. Placentas from healthy women were collected at the time of term delivery. Chorionic plate arteries were identified, excised, and cut into small pieces.