Mechanisms, potential treatment and biomarkers of abdominal aortic aneurysm

Title [sv]

Abstract [sv]

Bakgrund:Abdominal aortic aneurysm is a pathological enlargement of the aorta that affects 20 million and is responsible for 200.000 deaths annually, worldwide. The pathophysiological mechanisms are poorly understood and the disease still lacks drug treatment options and biomarkers to distinguish those with aneurysms that will grow fast. We have previously shown that there is a metabolic reprogramming in the diseased aorta contributing to chronic inflammation and weakening of the aortic wall.Målsättning:The research program aims to clarify novel pathophysiological mechanisms contributing to vascular metabolic dysfunction by manipulating novel pathways using existing clinically available drugs, i.e. semaglutide and a TRPV1 antagonist. The hypothesis is that these drugs will inhibit aneurysm formation. We will also screen for 100.000 of small RNAs as novel plasma biomarkers to identify patients with rapidly progressing aneurysms associated with severe disease progression that risk to rupture. The hypothesis is that there are specific markers that will predict the growth or stability of the aneurysms.Arbetsplan:To complete this research program, we will apply a translational experimental approach using blood and tissue samples from several hundred of available patients and controls, and use transgenic mice models of aneurysm formation, with state-of-the-art experimental approaches. This research program will lead to new knowledge in pathogenesis of aneurysm disease and aspires to develop new tools for diagnosis, prognosis and treatment of aneurysmal disease. The project will be completed within a 3 years and preliminary results supports the aim and hypothesis and the feasability to complete this project.Betydelse:There are clinically available drugs for other indications that can potentially modify the pathways that are investigated. Results from the proposed research program could therefore be quickly translated for treatment of aneurysm, which would revolutionize the field. Finding patients that have fast growing aneurysms that risk to rupture would help to implement personalized treatment and also ti identify those with stable aneurysms but this is not currently known on beforehand.

Abstract [en]

Bakgrund:Abdominal aortic aneurysm is a pathological enlargement of the aorta that affects 20 million and is responsible for 200.000 deaths annually, worldwide. The pathophysiological mechanisms are poorly understood and the disease still lacks drug treatment options and biomarkers to distinguish those with aneurysms that will grow fast. We have previously shown that there is a metabolic reprogramming in the diseased aorta contributing to chronic inflammation and weakening of the aortic wall.Målsättning:The research program aims to clarify novel pathophysiological mechanisms contributing to vascular metabolic dysfunction by manipulating novel pathways using existing clinically available drugs, i.e. semaglutide and a TRPV1 antagonist. The hypothesis is that these drugs will inhibit aneurysm formation. We will also screen for 100.000 of small RNAs as novel plasma biomarkers to identify patients with rapidly progressing aneurysms associated with severe disease progression that risk to rupture. The hypothesis is that there are specific markers that will predict the growth or stability of the aneurysms.Arbetsplan:To complete this research program, we will apply a translational experimental approach using blood and tissue samples from several hundred of available patients and controls, and use transgenic mice models of aneurysm formation, with state-of-the-art experimental approaches. This research program will lead to new knowledge in pathogenesis of aneurysm disease and aspires to develop new tools for diagnosis, prognosis and treatment of aneurysmal disease. The project will be completed within a 3 years and preliminary results supports the aim and hypothesis and the feasability to complete this project.Betydelse:There are clinically available drugs for other indications that can potentially modify the pathways that are investigated. Results from the proposed research program could therefore be quickly translated for treatment of aneurysm, which would revolutionize the field. Finding patients that have fast growing aneurysms that risk to rupture would help to implement personalized treatment and also ti identify those with stable aneurysms but this is not currently known on beforehand.

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Uppsala University

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Hjärt-Lungfonden

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