Forsøksdyr: Effect of NAD+ repletion on progression of atherosclerosis

Godkjenningsdato 18.05.2018

Atherosclerosis is the leading cause of mortality and morbidity in the world, often related to lifestyle diseases. Therefore, research that leads to development of new therapy has potentially huge impact for both patients and society. Although studies of atherosclerosis have shed light on some aspects of the cellular- and molecular dysfunctions resulting in the development and progression of atherosclerosis, we are still far from fully understanding this disease.

Recent studies indicate that reduced levels of NAD+ may be involved in the pathogenesis of lifestyle disease, such as atherosclerosis. Nicotinamide riboside (NR) was identified as a NAD+ precursor, with conserved metabolism from yeast to mammals. NR is found in milk, constituting a dietary source for NAD+ production. Our previous experiments show that NR can increase the NAD+ level both in vitro and in vivo.

Ldlr-KO mice are a well characterized model prone to atherosclerotic lesion formation. The purpose of this study is to examine the effects of NR on atherosclerosis development in Ldlr KO mice fed a western diet.

We will study development of atherosclerotic lesions in the aortic root, the aortic arch and in the common carotid artery. Atherosclerotic lesions occur spontaneous in the aortic root and the aortic arch in the Ldlr-KO mice, while atherosclerotic lesions in the common carotid artery will be stimulated by a surgical method called carotid cuff implantation. As with all surgery, some discomfort to the animals must be expected in the hours post-surgery. We will apply analgesic treatments to minimize the pain/discomfort and closely monitor them after surgery. After recovery, mice show normal behavior.

Mice will be sacrificed at designated time-points post-operation. Our experimental setup requires a total of 525 mice. To minimize the numbers of mice needed, all participants will be trained before the start of this study by the specialist in our department to assure that variation and drop out of animals are as low as possible.

The research outcome will help us understand more about the role of NR plays in metabolic system and uncover the potential treatment effects of NR on atherosclerosis. We expected no adverse effects on the animals.