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- W2912695998 abstract "Background and Purpose Apelin is an endogenous vasodilatory and inotropic peptide that is down-regulated in human pulmonary arterial hypertension, although the density of the apelin receptor is not significantly attenuated. We hypothesised that a G protein-biased apelin analogue MM07, which is more stable than the endogenous apelin peptide, may be beneficial in this condition with the advantage of reduced β-arrestin-mediated receptor internalisation with chronic use. Experimental Approach Male Sprague–Dawley rats received either monocrotaline to induce pulmonary arterial hypertension or saline and then daily i.p. injections of either MM07 or saline for 21 days. The extent of disease was assessed by right ventricular catheterisation, cardiac MRI, and histological analysis of the pulmonary vasculature. The effect of MM07 on signalling, proliferation, and apoptosis of human pulmonary artery endothelial cells was investigated. Key Results MM07 significantly reduced the elevation of right ventricular systolic pressure and hypertrophy induced by monocrotaline. Monocrotaline-induced changes in cardiac structure and function, including right ventricular end-systolic and end-diastolic volumes, ejection fraction, and left ventricular end-diastolic volume, were attenuated by MM07. MM07 also significantly reduced monocrotaline-induced muscularisation of small pulmonary blood vessels. MM07 stimulated endothelial NOS phosphorylation and expression, promoted proliferation, and attenuated apoptosis of human pulmonary arterial endothelial cells in vitro. Conclusion and Implications Our findings suggest that chronic treatment with MM07 is beneficial in this animal model of pulmonary arterial hypertension by addressing disease aetiology. These data support the development of G protein-biased apelin receptor agonists with improved pharmacokinetic profiles for use in human disease." @default.
- W2912695998 created "2019-02-21" @default.
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- W2912695998 date "2019-04-01" @default.
- W2912695998 modified "2023-10-18" @default.
- W2912695998 title "A novel cyclic biased agonist of the apelin receptor, MM07, is disease modifying in the rat monocrotaline model of pulmonary arterial hypertension" @default.
- W2912695998 cites W1480257879 @default.
- W2912695998 cites W1609108565 @default.
- W2912695998 cites W1824340961 @default.
- W2912695998 cites W1869368544 @default.
- W2912695998 cites W1899124983 @default.
- W2912695998 cites W1982661764 @default.
- W2912695998 cites W1987893946 @default.
- W2912695998 cites W1988934276 @default.
- W2912695998 cites W1991082553 @default.
- W2912695998 cites W1991916229 @default.
- W2912695998 cites W2002925464 @default.
- W2912695998 cites W2022701671 @default.
- W2912695998 cites W2027554054 @default.
- W2912695998 cites W2032033480 @default.
- W2912695998 cites W2033286860 @default.
- W2912695998 cites W2034146384 @default.
- W2912695998 cites W2038311789 @default.
- W2912695998 cites W2060165446 @default.
- W2912695998 cites W2067413933 @default.
- W2912695998 cites W2069248844 @default.
- W2912695998 cites W2074356238 @default.
- W2912695998 cites W2087276894 @default.
- W2912695998 cites W2100220436 @default.
- W2912695998 cites W2107821473 @default.
- W2912695998 cites W2109058223 @default.
- W2912695998 cites W2114552998 @default.
- W2912695998 cites W2117357690 @default.
- W2912695998 cites W2120154717 @default.
- W2912695998 cites W2120593855 @default.
- W2912695998 cites W2127686513 @default.
- W2912695998 cites W2131290734 @default.
- W2912695998 cites W2132493114 @default.
- W2912695998 cites W2133931336 @default.
- W2912695998 cites W2134915108 @default.
- W2912695998 cites W2136978968 @default.
- W2912695998 cites W2137186106 @default.
- W2912695998 cites W2147196684 @default.
- W2912695998 cites W2152479803 @default.
- W2912695998 cites W2157122261 @default.
- W2912695998 cites W2165885842 @default.
- W2912695998 cites W2170793571 @default.
- W2912695998 cites W2236862042 @default.
- W2912695998 cites W2240555926 @default.
- W2912695998 cites W2461543666 @default.
- W2912695998 cites W2476813941 @default.
- W2912695998 cites W2512819857 @default.
- W2912695998 cites W2557947909 @default.
- W2912695998 cites W2583089302 @default.
- W2912695998 cites W2591863096 @default.
- W2912695998 cites W2594466485 @default.
- W2912695998 cites W2598860758 @default.
- W2912695998 cites W2615284011 @default.
- W2912695998 cites W2745684430 @default.
- W2912695998 cites W2756104676 @default.
- W2912695998 cites W2765684626 @default.
- W2912695998 cites W2765693948 @default.
- W2912695998 cites W2766119667 @default.
- W2912695998 cites W2766306821 @default.
- W2912695998 cites W2767077155 @default.
- W2912695998 cites W2771328536 @default.
- W2912695998 cites W2897274766 @default.
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- W2912695998 doi "https://doi.org/10.1111/bph.14603" @default.
- W2912695998 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6468262" @default.
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