Olli Metsälä
University of Turku
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Featured researches published by Olli Metsälä.
Cardiovascular Diabetology | 2016
Sanna Hellberg; Johanna M. U. Silvola; Max Kiugel; Heidi Liljenbäck; Olli Metsälä; Tapio Viljanen; Jari Metso; Matti Jauhiainen; Pekka Saukko; Pirjo Nuutila; Seppo Ylä-Herttuala; Juhani Knuuti; Anne Roivainen; Antti Saraste
BackgroundDiabetes is a risk factor for atherosclerosis associated with oxidative stress, inflammation and cell proliferation. The purpose of this study was to evaluate arterial choline uptake and its relationship to atherosclerotic inflammation in diabetic and non-diabetic hypercholesterolemic mice.MethodsLow-density lipoprotein-receptor deficient mice expressing only apolipoprotein B100, with or without type 2 diabetes caused by pancreatic overexpression of insulin-like growth factor II (IGF-II/LDLR−/−ApoB100/100 and LDLR−/−ApoB100/100) were studied. Distribution kinetics of choline analogue 18F-fluoromethylcholine (18F-FMCH) was assessed in vivo by positron emission tomography (PET) imaging. Then, aortic uptakes of 18F-FMCH and glucose analogue 18F-fluorodeoxyglucose (18F-FDG), were assessed ex vivo by gamma counting and autoradiography of tissue sections. The 18F-FMCH uptake in atherosclerotic plaques was further compared with macrophage infiltration and the plasma levels of cytokines and metabolic markers.ResultsThe aortas of all hypercholesterolemic mice showed large, macrophage-rich atherosclerotic plaques. The plaque burden and densities of macrophage subtypes were similar in diabetic and non-diabetic animals. The blood clearance of 18F-FMCH was rapid. Both the absolute 18F-FMCH uptake in the aorta and the aorta-to-blood uptake ratio were higher in diabetic than in non-diabetic mice. In autoradiography, the highest 18F-FMCH uptake co-localized with macrophage-rich atherosclerotic plaques. 18F-FMCH uptake in plaques correlated with levels of total cholesterol, insulin, C-peptide and leptin. In comparison with 18F-FDG, 18F-FMCH provided similar or higher plaque-to-background ratios in diabetic mice.ConclusionsType 2 diabetes enhances the uptake of choline that reflects inflammation in atherosclerotic plaques in mice. PET tracer 18F-FMCH is a potential tool to study vascular inflammation associated with diabetes.
Journal of Translational Medicine | 2017
Maria Grönman; Miikka Tarkia; Tuomas Kiviniemi; Paavo Halonen; Antti Kuivanen; Timo Savunen; Tuula Tolvanen; Jarmo Teuho; Meeri Käkelä; Olli Metsälä; Mikko Pietilä; Pekka Saukko; Seppo Ylä-Herttuala; Juhani Knuuti; Anne Roivainen; Antti Saraste
BackgroundRadiolabeled RGD peptides detect αvβ3 integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [68Ga]NODAGA-RGD detects increased αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αvβ3 integrin is expressed in viable ischemic or injured myocardium.MethodsWe studied 8 Finnish landrace pigs 13xa0±xa04xa0days after percutaneous implantation of a bottleneck stent in the proximal left anterior descending coronary artery. Antithrombotic therapy was used to prevent stent occlusion. Myocardial uptake of [68Ga]NODAGA-RGD (290xa0±xa031xa0MBq) was evaluated by a 62xa0min dynamic PET scan. The ischemic area was defined as the regional perfusion abnormality during adenosine-induced stress by [15O]water PET. Guided by triphenyltetrazolium chloride staining, tissue samples from viable and injured myocardial areas were obtained for autoradiography and histology.ResultsStent implantation resulted in a partly reversible myocardial perfusion abnormality. Compared with remote myocardium, [68Ga]NODAGA-RGD PET showed increased tracer uptake in the ischemic area (ischemic-to-remote ratio 1.3xa0±xa00.20, pxa0=xa00.0034). Tissue samples from the injured areas, but not from the viable ischemic areas, showed higher [68Ga]NODAGA-RGD uptake than the remote non-ischemic myocardium. Uptake of [68Ga]NODAGA-RGD correlated with immunohistochemical detection of αvβ3 integrin that was expressed in the injured myocardial areas.ConclusionsCardiac [68Ga]NODAGA-RGD PET demonstrates increased myocardial αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [68Ga]NODAGA-RGD uptake indicates that it reflects αvβ3 integrin expression associated with repair of recent myocardial injury.
PLOS ONE | 2015
Miikka Tarkia; Antti Saraste; Christoffer Stark; Tommi Vähäsilta; Timo Savunen; Marjatta Strandberg; Virva Saunavaara; Tuula Tolvanen; Jarmo Teuho; Mika Teräs; Olli Metsälä; Petteri Rinne; Ilkka Heinonen; Nina Savisto; Mikko Pietilä; Pekka Saukko; Anne Roivainen; Juhani Knuuti
Objective Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model. Methods First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG). Results Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4). Conclusions We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.
WOS | 2017
Mia Ståhle; Sanna Hellberg; Jenni Virta; Heidi Liljenbäck; Olli Metsälä; Matti Jauhiainen; Pekka Saukko; Seppo Ylä-Herttuala; Pirjo Nuutila; Juhani Knuuti; Antti Saraste; Anne Roivainen
Atherosclerosis | 2017
Mia Ståhle; Sanna Hellberg; Jenni Virta; Heidi Liljenbäck; Olli Metsälä; Matti Jauhiainen; Pekka Saukko; Seppo Ylä-Herttuala; Pirjo Nuutila; Juhani Knuuti; Antti Saraste; Anne Roivainen
WOS | 2016
Johanna M. U. Silvola; Helena E. Virtanen; Riikka Siitonen; Sanna Hellberg; Heidi Liljenbäck; Olli Metsälä; Mia Ståhle; Tiina Saanijoki; Meeri Käkelä; Harri Hakovirta; Seppo Ylä-Herttuala; Pekka Saukko; Matti Jauhiainen; Tibor Z. Veres; Sirpa Jalkanen; Juhani Knuuti; Antti Saraste; Anne Roivainen
PLOS ONE | 2015
Miikka Tarkia; Antti Saraste; Christoffer Stark; Tommi Vähäsilta; Timo Savunen; Marjatta Strandberg; Virva Saunavaara; Tuula Tolvanen; Jarmo Teuho; Mika Teräs; Olli Metsälä; Petteri Rinne; Ilkka Heinonen; Nina Savisto; Mikko Pietilä; Pekka Saukko; Anne Roivainen; Juhani Knuuti
PLOS ONE | 2015
Miikka Tarkia; Antti Saraste; Christoffer Stark; Tommi Vähäsilta; Timo Savunen; Marjatta Strandberg; Virva Saunavaara; Tuula Tolvanen; Jarmo Teuho; Mika Teräs; Olli Metsälä; Petteri Rinne; Ilkka Heinonen; Nina Savisto; Mikko Pietilä; Pekka Saukko; Anne Roivainen; Juhani Knuuti
Society of Nuclear Medicine Annual Meeting Abstracts | 2014
Mia Ståhle; Ville Kytö; Heidi Liljenbäck; Max Kiugel; Olli Metsälä; Meeri Käkelä; Pekka Saukko; Juhani Knuuti; Anne Roivainen; Antti Saraste
Circulation | 2014
Miikka Tarkia; Antti Saraste; Christoffer Stark; Tommi Vähäsilta; Timo Savunen; Marjatta Strandberg; Virva Saunavaara; Tuula Tolvanen; Jarmo Teuho; Mika Teräs; Olli Metsälä; Petteri Rinne; Ilkka Heinonen; Nina Sarja; Mikko Pietilä; Pekka Saukko; Anne Roivainen; Juhani Knuuti