There is an inverse relationship between serum uric acid concentrations and measures of functional capacity in patients with cardiac failure. The strong correlation between serum uric acid and MVO2 suggests that in chronic heart failure, serum uric acid concentrations reflect an impairment of oxidative metabolism.

Vascular remodelling occurs during all stages of atherosclerotic progression. Anti-atherosclerotic drugs may function by restoring regulation of the processes involved in remodelling of the extracellular matrix. A key group of enzymes involved in these processes are the matrix metalloproteinases (MMPs). Oestrogens have been demonstrated to possess anti-atherosclerotic properties at low concentrations while being associated with lesion formation at high concentrations. We examined the effect of 17beta-oestradiol on MMP-2 expression in human coronary artery (CAVSMC) and umbilical artery vascular smooth muscle cells (UAVSMC). MMP-2 expression was measured by chemiluminescent immunoblotting and quantified by laser densitometry. pro-MMP-2 was secreted by VSMCs and increasing levels of 17beta-oestradiol, from physiological through supraphysiological, were associated with significant dose-dependent increases in MMP-2 levels in culture media. This effect was dependent on de novo protein synthesis and could be antagonised by the oestrogen receptor antagonist, tamoxifen, and the specific receptor antagonist ICI 182, 780. 17beta-Oestradiol appears to be a specific stimulator of MMP-2 release from human vascular cells. The concentration dependence of this effect suggests a basis for the differential effects of low and high oestrogen levels on vascular integrity.

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Oestrogen is believed to possess cardiovascular protective properties. Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen for vascular smooth muscle cells. We have investigated release of ET-1 from human endothelial cells in response to 17b-oestradiol. Serum was found to stimulate significantly ET-1 release during the first 4 h of culture. 17b-Oestradiol significantly reduced ET-1 immunoreactivity in the media of treated cells by up to 49% of control values after 4 h. This effect was found to be inversely related to the dose of 17b-oestradiol. Significant dose-dependent increases in nitric oxide synthase expression were observed in response to oestrogen after 24 h but not after 4 h. Serum-free experiments demonstrated that low doses of oestrogen were able to inhibit thrombin-induced ET-1 release whilst supraphysiological levels did not. These results provide a further perspective on the ability of oestrogens to maintain vascular health.