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. We found that the number of neutrophils per vessel and the percentage and intensity of vessel staining for CD66b, NF-kappaB and COX-2 were greatest in obese women and least in normal weight women, and that neutrophil infiltration and vascular inflammation significantly correlated with body mass index (BMI) and blood pressure. These data may help explain the relationship between obesity and hypertensive disorders.

Activation of NF-kappaB and expression of COX-2 in association with neutrophil infiltration in systemic vascular tissue of women with preeclampsia.

OBJECTIVE: The purpose of this study was to determine whether activation of NF-kappaB and expression of COX-2 are associated with neutrophil infiltration in systemic vascular tissue of women with preeclampsia. STUDY DESIGN: Subcutaneous fat biopsies were obtained at cesarean section or abdominal surgery from preeclamptic women (n = 7), normal pregnant women (n = 6), and normal nonpregnant women (n = 5). Resistance-sized vessels (10 to 200 microm) in subcutaneous fat were evaluated using immunohistochemical staining for: (1) CD66b, a neutrophil antigen, (2) nuclear factor-kappaB (NF-kappaB), a transcription factor for genes of inflammation, and (3) cyclooxygenase-2 (COX-2), an inflammatory gene product. RESULTS: The percentage of vessels which showed staining for CD66b, NF-kappaB, and COX-2 was significantly greater for preeclamptic patients as compared to normal nonpregnant or normal pregnant patients. In preeclamptic patients, vessel staining for NF-kappaB and COX-2 was present in both endothelium and in vascular smooth muscle. Leukocytes in the lumen and adhered to endothelium also stained for NF-kappaB and COX-2. Activation of NF-kappaB and expression of COX-2 were coincident with neutrophil flattening and adherence to endothelium and infiltration into the intimal space. CONCLUSION: These data demonstrate activation of NF-kappaB and expression of COX-2 in systemic vasculature of women with preeclampsia, and they demonstrate that this vascular inflammation is linked with neutrophil infiltration. Neutrophil release of toxic substances, such as reactive oxygen species, TNFalpha and thromboxane, could be responsible for vasoconstriction and vascular dysfunction. These data clearly place preeclampsia in the category of an inflammatory disease associated with immune dysfunction.