title: Long-term methionine-diet induced mild hyperhomocysteinemia associated cardiac metabolic dysfunction in multiparous rats.
abstract: Mild hyperhomocysteinemia (HHcy, clinically defined as less than 30 μmol/L) is an independent cardiovascular disease (CVD) risk factor, and is associated with many complications during pregnancy, such as preeclampsia (PE). The aim of this study was to assess the effect of long-term mild HHcy on cardiac metabolic function of multiparous rats. Female rats were mated 3 to 4 times and were fed with methionine in drinking water to increase plasma Hcy (2.9 ± 0.3 to 10.5 ± 2.3 μmol/L) until termination. This caused significant increase of heart weight/body weight (0.24 ± 0.01 to 0.27 ± 0.01 g/100 g) and left ventricle weight (0.69 ± 0.03 to 0.78 ± 0.01 g). Superoxide production was increased by 2.5-fold in HHcy hearts using lucigenin chemiluminescence. The ability of bradykinin and carbachol to regulate myocardial oxygen consumption (MVO2) in vitro was impaired by 59% and 66% in HHcy heart, and it was restored by ascorbic acid (AA), tempol, or apocynin (Apo). Protein expression of p22(phox) subunit of NAD(P)H oxidase was increased by 2.6-fold, but there were no changes in other NAD(P)H oxidase subunits, NOSs or SODs. Microarray revealed 1518 genes to be differentially regulated (P < 0.05). The mRNA level of NAD(P)H oxidase subunits, NOSs or SODs remained unchanged. In conclusion, long-term mild HHcy increases cardiac superoxide mainly through regulation of p22(phox) component of the NAD(P)H oxidase and impairs the ability of NO to regulate MVO2 in heart of multiparous mothers.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York, 10595, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York, 10595, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kertowidjojo
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York, 10595, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ojaimi
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York, 10595, USA.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martin-Fernandez
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York, 10595, USA.
authors.forename: Sharath
authors.initials: S
authors.lastname: Kandhi
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York, 10595, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wolin
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York, 10595, USA Thomas_hintze@nymc.edu.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hintze
keywords: Mild hyperhomocysteinemia; NAD(P)H oxidase; multiparous; nitric oxide; superoxide