Cardiovascular and metabolomic profiling of osteoarthritis
Kuupäev
2017-11-14
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Osteoartroos on krooniline liigeshaigus, mis haarab sagedamini käe-, põlve-, puusa- ja lülisamba liigeseid ning põhjustab valu ja liigesliikuvuse piiratust. Osteoartroosiga patsientide arv on suur ning tegemist on kõige kiiremini kasvava liigeshaiguse patsiendigrupiga. Tänaseni puudub haiguse tekkemehhanismidest piisav arusaam, et efektiivselt pidurdada haiguse kulgu. Osteoartroosi on pikalt peetud kõhre mehhaanilisest kulumisest tingitud haiguseks, aga viimastel aastatel on ilmnenud üha rohkem tõendeid, et haiguse arengus mängivad olulist rolli süsteemne alaäge põletik, muutused ainevahetuses ja arterite jäikuses. Osteoartroosiga patsientidel on leitud kõrgem südame- ja veresoonkonna haiguste risk, kuid täpsemad mehhanismid selle võimaliku seose taga on teadmata. Selle doktoritöö eesmärgiks oli selgitada osteoartroosi ja arterite funktsiooni ning oksüdatiivse stressi ja ainevahetushäirete (sh metaboolse sündroomi) vahelisi seoseid. Lisaks oli eesmärgiks kirjeldada osteoartroosi lipiidide ainevahetusega seotud madalmolekulaarsete ühendite profiili.
Selle doktoritöö raames läbiviidud uuringusse kaasati 70 lõppstaadiumis osteoartroosiga patsienti Tartu Ülikooli Kliinikumi ortopeedia osakonnast ning kontrollgruppi 82 ilma osteoartroosita uuritavat Tartumaa perearstide nimistutest. Arterite jäikuse mõõtmised tehti Endoteeli Keskuses ning biokeemiliste markerite mõõtmised TÜ Kliinikumi ühendlaboris ning bio- ja siirdemeditsiini instituudi biokeemia osakonnas.
Töö tulemusena leidsime uudse seose aordi jäikuse ja osteoartroosi raskusastme vahel. Osteoartroosiga patsientide arterid olid võrreldes kontrollgrupi liikmete arteritega jäigenenud. Lisaks leidsime, et osteoartroosi korral esineb organismis kõrgem oksüdatiivse stressi tase, mis on seotud ka osteoartroosi raskusastmega. Kirjeldasime, et osteoartroosi korral esinevad lipiidide ainevahetuse häired, mis on seotud arterite funktsiooniga ja aitavad selgitada osteoartroosi ning südame- ja veresoonkonnahaiguste vahelist seost. Selle uuringu tulemusena tuvastatud seosed osteoartroosi ja lipiidide ainevahetuse, oksüdatiivse stressi ja arterite funktsiooni vahel võivad tulevikus aidata välja töötada uusi ründepunkte osteoartroosi ravimisel.
Osteoarthritis is a chronic joint disease that most frequently affects the hand, knee and hip joints, and the spine. Osteoarthritis manifests mainly as pain and serious loss of function. The prevalence of osteoarthritis is high and it is the fastest growing musculoskeletal disorder. Furthermore, osteoarthritis is the leading cause of pain in elderly. There is no cure for the disease and treatment focuses on pain relief and on preserving the function of affected joints. For a long time osteoarthritis was thought to be a non-inflammatory degenerative „wear and tear“ disease of the articular cartilage. However, in recent years several studies have found that systemic low-grade inflammation, metabolic disturbances and arterial dysfunction are involved in development of osteoarthritis. Osteoarthritis patients have increased cardiovascular disease risk, but the mechanisms behind the association are largely unknown. The aims of this thesis were to determine associations between osteoarthritis, and arterial function, metabolic disturbances and oxidative stress. In addition, we aimed to describe the metabolic profile of low molecular weight lipid related compunds in osteoarthritis patients. Seventy end-stage knee and hip osteoarthritis patients from the department of orthopaedics of Tartu University Hospital and 82 non-osteoarthritis controls from the same geographic regioon were enrolled in the study. Measurements of arterial stiffness were conducted at the Endothelial Centre, University of Tartu. Biochemical markers were measured at the Department of Biochemistry, Institute of Biomedicine and Translational Medicine and at the United Laboratories of the University of Tartu. As a result of the study, we found that severity of osteoarthritis was associated with aortic stiffness. The arterial stiffness of the osteoarthritis patients was significantly higher compared with the controls. In addition, the level of oxidative stress was higher in the osteoarthritis patients and correlated with severity of osteoarthritis. We found that lipid metabolism was associated with osteoarthritis and also with arterial stiffness, which might hence explain the association between osteoarthritis and cardiovascular disease. In conclusion, this thesis describes associations of osteoarthritis with arterial stiffness, high-grade oxidative stress and lipid metabolism and might help to design new targets in finding cure for the disease.
Osteoarthritis is a chronic joint disease that most frequently affects the hand, knee and hip joints, and the spine. Osteoarthritis manifests mainly as pain and serious loss of function. The prevalence of osteoarthritis is high and it is the fastest growing musculoskeletal disorder. Furthermore, osteoarthritis is the leading cause of pain in elderly. There is no cure for the disease and treatment focuses on pain relief and on preserving the function of affected joints. For a long time osteoarthritis was thought to be a non-inflammatory degenerative „wear and tear“ disease of the articular cartilage. However, in recent years several studies have found that systemic low-grade inflammation, metabolic disturbances and arterial dysfunction are involved in development of osteoarthritis. Osteoarthritis patients have increased cardiovascular disease risk, but the mechanisms behind the association are largely unknown. The aims of this thesis were to determine associations between osteoarthritis, and arterial function, metabolic disturbances and oxidative stress. In addition, we aimed to describe the metabolic profile of low molecular weight lipid related compunds in osteoarthritis patients. Seventy end-stage knee and hip osteoarthritis patients from the department of orthopaedics of Tartu University Hospital and 82 non-osteoarthritis controls from the same geographic regioon were enrolled in the study. Measurements of arterial stiffness were conducted at the Endothelial Centre, University of Tartu. Biochemical markers were measured at the Department of Biochemistry, Institute of Biomedicine and Translational Medicine and at the United Laboratories of the University of Tartu. As a result of the study, we found that severity of osteoarthritis was associated with aortic stiffness. The arterial stiffness of the osteoarthritis patients was significantly higher compared with the controls. In addition, the level of oxidative stress was higher in the osteoarthritis patients and correlated with severity of osteoarthritis. We found that lipid metabolism was associated with osteoarthritis and also with arterial stiffness, which might hence explain the association between osteoarthritis and cardiovascular disease. In conclusion, this thesis describes associations of osteoarthritis with arterial stiffness, high-grade oxidative stress and lipid metabolism and might help to design new targets in finding cure for the disease.
Kirjeldus
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Märksõnad
osteoartroos, biomarkerid, arterioskleroos, leptiin, adiponektiin, ainevahetussündroom, oksüdatiivne stress, osteoarthrosis, biomarkers, arteriosclerosis, leptin, adiponectin, metabolic syndrome, oxidative stress