Long-term Ang (1-7) treatment caused both vasoprotection, via improvement in endothelial function, and atheroprotection, with a reduction in lesion progression in a model of atherosclerosis. These effects appear to be mediated by the restoration of nitric oxide bioavailability and involve a complex interaction of both Mas and AT(2) receptors.

Is it difficult being a woman scientist?" the biochemist Dorothy Crowfoot Hodgkin was asked at high table dinner in an Oxford college by the man sitting next to her. "Not since I won the Nobel Prize," she replied. 1 In 1964, the British press had reacted to her award with the headlines: "Oxford housewife wins Nobel" and "British woman wins Nobel Prize-£18 750 prize to mother of three." 2 While such overtly sexist treatment of female scientists by the media is now rare, progress towards gender equality in universities has been astonishingly slow. A UK parliamentary inquiry into women in scientific careers found that with only 17% of professors in science, technology, engineering, and mathematics (STEM) in 2011-12 women were still under-represented at senior levels across all STEM disciplines. 3 Concerned with the sustainability of increasing the scientific workforce, the inquiry concluded that efforts to inspire more women into science were wasted if they were subsequently disadvantaged compared with men and recommended that universities should do more to support and retain women in scientific careers. 3

1. Many studies have evaluated the effectiveness of alpha-tocopherol (vitamin E) in the development and progression of cardiovascular diseases, with conflicting results reported on the protective effect of this anti-oxidant. 2. The present study examined the effectiveness of a novel tocopheryl phosphate mixture (TPm) compared with that of alpha-tocopherol (TA) on key pro-inflammatory markers involved in atherogenesis, including interleukin (IL)-1beta, IL-6, IL-8, plasminogen activator inhibitor-1, tumour necrosis factor-alpha and C-reactive protein (CRP), as well as vascular function and lesion development in rabbits fed a 2% cholesterol diet. 3. Treatment with TPm, incorporated into the rabbit food at four doses ranging from 60 to 360 mg/kg chow, resulted in a significant reduction in plasma levels of all pro-inflammatory cytokines and biomarkers that appeared to be somewhat dose dependent. Conversely, treatment with TA, at a dose equivalent to the highest dose of TPm used, only decreased plasma levels of CRP, IL-6 and IL-8. Both TPm and TA treatment significantly improved vascular function to a similar extent, although TPm was more effective in reducing lesion development. 4. The reduction in these key pro-inflammatory markers appears to follow the improvement in the atherogenic state of the animals, indicating that the anti-inflammatory properties of TPm may be potentially beneficial in inflammatory disease states.

The aim of this study was to investigate the effects of Angiotensin (Ang) (1‐7), a Mas receptor agonist, and CGP42112, an AT2 receptor agonist, in a setting of atherosclerosis. All treatments were investigated using apolipoprotein E‐deficient (ApoE−/−) mice fed a high fat diet for 16 weeks, with chronic treatment administered in final 4 weeks via osmotic mini‐pumps. Treatments were either: saline (vehicle), Ang (1‐7) (24µg/kg/hr) or CGP42112 (1µg/kg/min) alone, as well each agonist in combination with either an AT2R antagonist, PD123329 (10mg/kg/day), or the MasR antagonist, A779 (48µg/kg/hr). Chronic treatment with either Ang (1‐7) or CGP42112 significantly improved endothelial function and decreased lesion development compared to vehicle treated mice. Superoxide levels were significantly reduced and eNOS expression increased with Ang (1‐7) and CGP42112 treatments when compared to vehicle treated mice. Ang (1‐7) effects were reversed with both AT2R and MasR blockede, however, CGP42112 mediated effects were only reversed by the AT2R antagonist. This study indicates that both Ang (1‐7) and CGP42112 improve endothelial function and reduce atherosclerotic lesions via either the AT2 or the Mas receptor, or both. This highlights the importance of gaining a better understanding of the role of AT2 and Mas receptors in atherosclerosis.NHMRC (Australia)

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