Gravin Scaffolding Protein Mediates Signaling in High Fat Diet Model

Abstract

Atherosclerosis is an inflammatory response principally in the walls of arteries contributing to cardiovascular related mortality, which can be induced by diets rich in fats. Gravin (AKAP12), an A‐kinase anchoring protein (AKAP), is targeted to specific intracellular locations with protein kinase A (PKA) as well as other signaling molecules. It has been shown that gravin can regulate cholesterol efflux and LDL receptor expression via SREBPS activation. The purpose of this study was to determine whether the absence of gravin mediated signaling would prevent atherosclerosis induced by a high fat diet. Five week‐old wild‐type (WT) and gravin‐knockout (KO) mice were subjected to high fat diet (HFD) or normal diet (ND) for 16 weeks. Lipid profile was measured via HPLC and arterial blood pressure was measured via a Millar catheter. Cholesterol, triglyceride and VLDL levels as well as systolic and diastolic pressure were significantly decreased in KO compared to WT treated with HFD (p<0.0001); no differences were observed between KO and WT with ND. This data indicates that the absence of gravin mediated signaling is able to decrease lipid metabolism as well as to lower the blood pressure in response to HFD.