Nya möjliga behandlingar av bukaortaaneurysm

Title [sv]

Abstract [sv]

Bakgrund:Cardiovascular disease, including abdominal aortic aneurysm (AAA), is an enormous health care burden and ruptured AAA account for approximately 200,000 of annual deaths. AAA is an inflammatory disease and despite long-term anti-inflammatory and lipid lowering treatment due to other underlying vascular disease the majority of AAA patients have, these drugs neither prevent nor inhibit aneurysm disease. Not a single drug treatment for aneurysm exist. This indicates that more specific immune cell targeting is required to inhibit aneurysm development.Målsättning:To be able to find new therapeutic preventive strategies the molecular mechanisms behind the disease and drug targets needs to be elucidated in more detail. Based on previous studies, supported by VR and HLF, me and my team have identified several key factors that could be targeted by certain drugs. The main aim is to clarify pathophysiological and molecular mechanisms behind AAA disease and to find novel treatment strategies.Arbetsplan:Human samples and cell and animal models of aneurysm disease will be used to target immune cell activation and vascular remodelling via transcriptional regulation and by targeting glycolysis and kinase activity of certain proteins by using specific microRNA and drug candidates. This autumn, one drug (metformin, with proven concept from pre-clinical experiments and reotrospective analysis in humans by my team) will be used in clinical trials. Along this, four other pre-clinical studies will be performed using combinational therapy of two different drugs with separate pathways (low dose imatinib+metformin), a novel neutrophil elastase inhibitor and a glycolysis inhibitor. Betydelse:The importance of this research is to increase the knowledge of pathogenesis of AAA so that standardized surgery can be replaced by individual risk-adapted medication resulting in reduced mortality and fewer complications leading to better quality of life.

Abstract [en]

Bakgrund:Cardiovascular disease, including abdominal aortic aneurysm (AAA), is an enormous health care burden and ruptured AAA account for approximately 200,000 of annual deaths. AAA is an inflammatory disease and despite long-term anti-inflammatory and lipid lowering treatment due to other underlying vascular disease the majority of AAA patients have, these drugs neither prevent nor inhibit aneurysm disease. Not a single drug treatment for aneurysm exist. This indicates that more specific immune cell targeting is required to inhibit aneurysm development.Målsättning:To be able to find new therapeutic preventive strategies the molecular mechanisms behind the disease and drug targets needs to be elucidated in more detail. Based on previous studies, supported by VR and HLF, me and my team have identified several key factors that could be targeted by certain drugs. The main aim is to clarify pathophysiological and molecular mechanisms behind AAA disease and to find novel treatment strategies.Arbetsplan:Human samples and cell and animal models of aneurysm disease will be used to target immune cell activation and vascular remodelling via transcriptional regulation and by targeting glycolysis and kinase activity of certain proteins by using specific microRNA and drug candidates. This autumn, one drug (metformin, with proven concept from pre-clinical experiments and reotrospective analysis in humans by my team) will be used in clinical trials. Along this, four other pre-clinical studies will be performed using combinational therapy of two different drugs with separate pathways (low dose imatinib+metformin), a novel neutrophil elastase inhibitor and a glycolysis inhibitor. Betydelse:The importance of this research is to increase the knowledge of pathogenesis of AAA so that standardized surgery can be replaced by individual risk-adapted medication resulting in reduced mortality and fewer complications leading to better quality of life.

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Uppsala University

Uppsala University

Uppsala University

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Hjärt-Lungfonden

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