These results demonstrate that during increased ventricular contraction, chronically decreased aortic distensibility contributes to a further decrease in the coronary flow reserve ratio, impairs endocardial blood flow and may induce subendocardial ischemia even in the absence of coronary artery stenosis.
Preeclampsia is a pregnancy-specific syndrome and a major cause of maternal mortality. The pathophysiology of preeclampsia is unknown, and no proteome analysis of preeclampsia has been reported. We sought to identify proteins associated with preeclampsia using a proteomic technique and performed two-dimensional electrophoresis (2-DE) on sera from six patients with preeclampsia and six normal pregnant women, followed by comparison of the SYPRO Ruby-stained 2-DE profiles. A group of overexpressed spots was identified in the limited study set. Overexpressed spots were identified as clusterin by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) followed by peptide mass fingerprinting, a protein database search, and Western blot analysis. Additionally, sera of 80 preeclamptic women and 80 normal pregnant women were processed by immunoassay methods to confirm changes in clusterin concentrations quantitatively. Immunoassays showed that clusterin levels in the 80 preeclamptic women were significantly higher than those in the 80 controls (mean +/- SD; 1.62 +/- 0.46 times reference level in preeclamptic women vs. 1.30 +/- 0.46 times reference level in controls, P < 0.001). Proteomic analysis of serum proteins is a promising tool for studying preeclampsia pathophysiology and identifying proteins associated with preeclampsia.
Preeclampsia is associated with thrombosis of the intervillous or spiral artery. A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 (PAI-1) gene is suggested to be involved in regulating the synthesis of the inhibitor, 4G allele, being associated with the enhanced gene expression and plasma PAI-1 levels. We assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI-1 gene in 115 preeclamptic patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of the homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women (P ϭ 0.04) or in the healthy volunteers (P ϭ 0.02). The 4G allele frequency was also significantly higher in the patients than in the control group of pregnant women (P ϭ 0.03) and in the healthy volunteers (P ϭ 0.02). These results suggest that the presence of the 4G/4G genotype of the PAI-1 gene is one of the risk factors for preeclampsia.
When the work of the heart is increased, a decrease in aortic compliance tends to compromise ischaemic myocardium further in the presence of an induced stenosis of a major coronary artery.
These findings indicate that ascorbate, an antioxidant, may prevent the development of nitrate tolerance during continuous nitrate therapy in patients with congestive heart failure.
These results indicate that platelet cGMP can be used as an indicator for in situ evaluation of nitroglycerin effects and that patients who have received nitrates develop nitrate tolerance, which affects intracellular production of cGMP and vasodilation in the response to nitroglycerin.
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