Gene sequencing and tissue expression of unknown isoforms of an angiotensin II type 2 receptor interacting protein, ATIP, in the rat.

To investigate the expression of the unknown angiotensin II type 2 receptor interacting protein (ATIP) isoforms in the rat we used the known sequences of human and mouse ATIP to design sequencing primers to enable us to sequence rat ATIP3 and ATIP4. Exon 4, which is present in human but not mouse ATIP, was not identified in the coding region of rat ATIP. The expression levels of these genes in a range of rat tissues were examined, and we concluded that there is little similarity in the relative tissue distribution of the various ATIP isoforms in rat and human.

Antiatherosclerotic and renoprotective effects of ebselen in the diabetic apolipoprotein E/GPx1-double knockout mouse.

Objective: To investigate the effect of the GPx1-mimetic ebselen on diabetes-associated atherosclerosis and renal injury in a model of increased oxidative stress.

Research Design And Methods: The study was performed using diabetic apolipoprotein E/GPx1 (ApoE(-/-)GPx1(-/-))-double knockout (dKO) mice, a model combining hyperlipidemia and hyperglycemia with increased oxidative stress. Mice were randomized into two groups, one injected with streptozotocin, the other with vehicle, at 8 weeks of age.

Cardiac inflammation associated with a Western diet is mediated via activation of RAGE by AGEs.

A diet high in fat induces cardiac hypertrophy, inflammation, and oxidative stress. Although such actions have largely been ascribed to fat deposition, the accumulation of advanced glycation end products (AGEs) and subsequent activation of the receptor for AGEs (RAGE) may also represent important mediators of cardiac injury following exposure to a Western diet. In this study, male C57BL6J and RAGE knockout mice were placed on either a standard diet (7% fat) or a Western "fast-food" diet (21% fat).

ACE2 deficiency modifies renoprotection afforded by ACE inhibition in experimental diabetes.

Objective: The degradation of angiotensin (Ang) II by ACE2, leading to the formation of Ang 1-7, is an important step in the renin-angiotensin system (RAS) and one that is significantly altered in the diabetic kidney. This study examines the role of ACE2 in early renal changes associated with diabetes and the influence of ACE2 deficiency on ACE inhibitor-mediated renoprotection.

Research Design And Methods: Diabetes was induced by streptozotocin in male c57bl6 mice and ACE2 knockout (KO) mice.

Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein E-deficient mice.

Background: Recent clinical studies have suggested a major protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx1) in diabetes-associated atherosclerosis. We induced diabetes in mice deficient for both GPx1 and apolipoprotein E (ApoE) to determine whether this is merely an association or whether GPx1 has a direct effect on diabetes-associated atherosclerosis.

Methods And Results: ApoE-deficient (ApoE-/-) and ApoE/GPx1 double-knockout (ApoE-/- GPx1-/-) mice were made diabetic with streptozotocin and aortic lesion formation, and atherogenic pathways were assessed after 10 and 20 weeks of diabetes.