Abstract P141: Gender Differences in the Development of Severe Pulmonary Hypertension and Right Ventricular Dysfunction in Apolipoprotein E--Deficient Mice Are Eliminated with Increasing Age

• Published in: Circulation research 2011-12, Vol.109 (suppl_1)
• Main Authors: Partow-Navid, Rod, Umar, Soban, Matori, Humann, Iorga, Andrea, Fogelman, Alan M, Navab, Mohamad, Eghbali, Mansoureh
• Format: Article
• Language: English
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.109.suppl_1.AP141

Abstract only Apolipoprotein E (ApoE) is a multifunctional protein and its deficiency leads to the development of atherosclerosis in mice. Patients with pulmonary hypertension (PH) have reduced expression of ApoE in lung tissue. ApoE is known to inhibit endothelial and smooth muscle cell proliferation and has anti-inflammatory and anti-platelet aggregation properties. Young ApoE deficient mice have been shown to develop high fat diet-induced PH in a gender specific manner. Estrous cyclicity peaks at 7–8 months and declines by 9 months of age in mice. Here we investigated the effects of monocrotaline (MCT) on young and middle-aged ApoE deficient mice.Middle-Aged (MA) (11–12 month old) male (n=4) and female (n=4) and young (7–8 month old) male (n=5) and female (n=5) ApoE deficient mice were injected with a single intraperitoneal dose of MCT (60 mg/kg). Mice were closely monitored for ∼4 weeks with serial echocardiography for cardiopulmonary hemodynamic assessment. Direct cardiac catheterisation was performed terminally to record peak systolic right ventricular pressure (RVP). RV, LV, IVS and lung tissue was dissected and weighed. Trichrome staining and histochemical analyses were performed. At ∼4 weeks after MCT, MA male and female and young male mice developed severe PH (RVP: MA male=64±5 mmHg, MA female=71±4 mmHg, young male=60±5 mmHg, p=n.s between all the groups) whereas young females developed significantly less severe PH (RVP: 37±5 mmHg, P