Abstract 289: Reduced Uterine Perfusion Pressure (RUPP) Elicits Increased sFlt-1 Levels Not Only In The Placenta But Also Adipose Tissue
Preeclampsia is a pregnancy-specific disorder characterized by new-onset hypertension. Placental ischemia is causative in this disorder with the release of antiangiogenic factors such as sFlt-1 into the maternal circulation promoting endothelial dysfunction and hypertension. Obesity is a major risk factor for preeclampsia, but the mechanisms are far less understood. Recent evidence suggests that adipose tissue is a source of sFlt-1. This study tested the hypothesis that placental ischemia produced by RUPP elicits an increase of sFlt-1 levels in both placental and adipose tissue from normal pregnant rats. Timed-pregnant Wistar-hannover rats (20 wks old) on NIH31 standard chow were subjected to RUPP (N=15) on gestational day (GD)14 or remained normal pregnant (NP, N=14). Rats were implanted with carotid catheters on GD18 and fasted overnight. On GD19, mean arterial blood pressure (MAP) was assessed in conscious, restrained rats. Statistical significance was P<0.05. MAP was greater in RUPP (114±2 v 101±1mmHg) with reduced fetal weight (1.73±0.02 v 1.88±0.01g) but similar placental weight (RUPP: 0.45±0.03 v NP: 0.47±0.03g). Although RUPP reduced body weight (297±7 v 343±6g), visceral adipose tissue weight was not altered (RUPP: 11.5±1 v NP: 13.2±1g). Total cholesterol was increased (RUPP: 223±35 v NP: 156±6mg/dL) but there was no difference in free fatty acids (RUPP: 8±2 v NP: 8±2mg/L) but reduced triglyceride levels (RUPP: 265±38 v RUPP: 659±100mg/dL). RUPP reduced leptin (3.2±0.2 v 4.2±0.4ng/mL) and adiponectin (2.8±0.2 v 3.3±0.2ug/mL) with increased fasting glucose levels (191±6 v 163±8mg/dL). Very interestingly, RUPP increased sFlt-1 levels in placenta (4702±375 v 3903±309pg/g tissue) and retroperitoneal adipose tissue (179±28 v 76±22pg/g tissue). These data indicate that RUPP-induced hypertension in normal pregnant rats promotes metabolic disturbances along with increases in sFlt-1 not only the placenta but in the adipose tissue. In conclusion, we propose that placental ischemia-induced hypertension is exaggerated in states linked to increased accumulation of adipose tissue, such as in diet-induced or genetic obesity, due to amplified metabolic derangements and increases in sFlt-1 levels from both placental and adipose sources.
Author Disclosures: F.T. Spradley: None. A.C. Palei: None. J.P. Granger: None.
- © 2014 by American Heart Association, Inc.