Forsøksdyr: Fibroseutvikling og hjertefunksjon i integrin a11-defekte og -overutrykkende mus, samt syndecan-4/a11 dobbel KO mus


Godkjenningsdato 04.04.2018

The purpose of this study is to better understand the way the heart is able to detect changes when subjected to increased stresses, such as high blood pressure (hypertension). In such conditions the heart can change structurally, to the detriment of the patient, such that targeting the proteins involved in this process of remodeling may be therapeutic.

To simulate the effects of hypertension on the heart we shall subject mice to aortic banding procedure. This surgery is conducted on sedated and anesthetized mice, which reduces the distress the animals are subject to. Our surgeons are highly experienced at handling animals and mice recover very quickly from the surgery, with no signs of pain or distress when the animals awaken from the operation.

This work will lead to the development of novel therapeutic drugs, which target the proteins responsible for the development of heart failure, specifically diastolic dysfunction (DD). DD is forecast to become the most common cause of heart failure and today there are very limited therapeutic options for patients suffering from this ultimately fatal condition. Indeed patients diagnosed with heart failure have poorer prognosis than most cancers today. There is therefore a strong need to develop new effective therapies to target this condition.

We shall use up to 2090 mice in this presented study. This number was determined from previous experience of the required animals to conduct the proposed experiments and the estimated survival of animals from the proposed surgical procedures.

We actively apply the 3 Rs to this research proposal. Through improvements in surgical methodology we have reduced the mortality associated with aortic banding, so that we can reduce the number of required animals for this study. We continue to replace mouse studies with in vitro experiments, however limited replication of the complex 3D environment of the heart means many of the existing methodologies are insufficient for studying disease mechanisms and therefore animal models are still required for understanding the development of heart failure.