In fact, the more significant hemodynamic effects of this agents, conveyed by TGF restoration, led to afferent arteriole vasoconstriction as compared to efferent vasodilation observed with RAS-inhibition ( Pre-clinical studies in genetically modified animal model of T2DM (OLETF rats, Otsuka Long Evans Tokushima fatty rats) have shown high PRA (plasmatic renin activity) levels, without any change in aldosterone levels under dapagliflozin chronic treatment, in accordance with the aforementioned observations of an independent intrarenal RAS ( Moreover, in recent years the use of small interfering RNAs (siRNA), selectively targeting AGT, as a novel approach of interfering with the RAS has shown beneficial cardio- and nephroprotective properties
(1) FSP1/AIFM2: FSP1 was originally classified as a caspase-independent apoptosis-inducing protein, on the basis of its sequence similarity to apoptosis-inducing factor 1 (AIFM1), and was annotated as a flavoprotein with NAD(P)H oxidase activity 38
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