Genetic markers of enzymatics in the pathogenesis of chronic obstructive pulmonary disease as a systemic disease and the effects of antioxidant peptides
Kuupäev
2025-01-23
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Tartu Ülikooli Kirjastus
Abstrakt
Krooniline obstruktiivne kopsuhaigus (KOK) on krooniline, ja süvenev haigus. KOK on maailmas juhtiv haigestumuse ja suremuse põhjus [1]. Prognooside kohaselt KOK-i levimus suureneb tänu rahvastiku vananemisele ja jätkuvale kokkupuutele KOK-i riskiteguritega [1,2]. KOK-i ägenemist iseloomustab hingamisteede sümptomite halvenemine või uute lisandumine ≤2 nädala jooksul [3].
Sigaretisuits kui KOK-i peamine riskitegur põhjustab oksüdatiivset stressi (OS) ja sellega seotud põletikku nii hingamisteedes kui kogu organismis [4]. OS kui vabade radikaalide ülekaal antioksüdantide üle mängib võtmerolli KOK-i tekkes ja süvenemises [5]. Seetõttu on äärmiselt oluline leida uusi teid KOK-i diagnoosimiseks ja ägenemiste ennetamiseks üle redoks-põletikuliste radade.
Oma töös keskendusime KOK-i süsteemsetele mõjudele ning näitasime, et DNA kahjustused ja parandusprotsessid süvenesid perifeerse vere rakkudes koos õhuvoolutakistuse suurenemisega hingamisteedes. DNA kahjustus oli veelgi suurem KOK-i ägenemise korral näidates, et KOK koormab kogu meie organismi. Lisaks näitasime, et teatud põletikku toetavad ensüümid olid üleekspresseeritud KOK-i patsientide vereringes. Samas olid põletikuvastased ensüümid alaekspresseeritud. Siiski, mitte kõikide ensüümide ekspressioon ei muutunud õhuvoolutakistuse suurenedes, sestap jääb alles küsimus kopsufunktsiooni languse või KOK-i tekke täpsete tegurite kohta.
Lõpuks selgitasime, kas sünteetilised antioksüdandid võiksid olla potentsiaalsed KOK-i ravimid suurendamaks antioksüdantset kaitset ja vähendamaks põletikulist vastust KOK-i korral. Leidsime, et hoolimata tugevatest antioksüdantsetest omadustest suurendasid nad kindlate põletikku toetavate ensüümide ekspressiooni. Seetõttu ei saa neid antioksüdante kasutada otse ravimitena, vaid pigem võtta aluseks potentsiaalsete KOK ravimite kavandamisel.
Chronic obstructive pulmonary disease (COPD) is a relentlessly progressive disease, one of the 3 leading causes of deaths and morbidity worldwide [1]. COPD is projected to increase in the coming decades because of continued exposure to risk factors and aging [1,2]. The largest COPD burden is attributed to acute exacerbations (AE-COPD), characterized by sudden worsening of respiratory symptoms over ≤2 weeks [3]. Cigarette smoke, the main risk factor of COPD, causes inflammation and oxidative stress (OS) both in the airways and in the whole body [4]. OS is a key player in the development and progression of COPD [5]. Thus, a strategy to diagnose and prevent COPD via redox-inflammatory path is a critical priority. We currently concentrated on systemic effects of COPD and showed that DNA damage and its reparation increased in peripheral blood cells, along with the progression of the airflow obstruction. The damage was even more severe amongst patients with AE-COPD, showing the incredible burden COPD brings about in the whole body. We also showed that some enzymes that fight the inflammation were expressed higher in COPD patients’ bloodstream, whereas other enzymes that facilitate resolving the inflammation were under-expressed. This overactivation of the redox-inflammatory axis and the inability to resolve it provides a new explanation for the vicious cycle of the development and progression of COPD. However, the expressions of not all enzymes changed as the airflow limitation progressed, raising questions as to what might be the associates of lung function decline and development of COPD. Lastly, we found that synthetic antioxidants, new therapeutic potentials, despite increasing the level of certain antioxidant enzymes, also increased the expression of some pro-inflammatory enzymes. Therefore, these cannot possibly be used directly as themselves, but could serve as a lead for designing further COPD therapies
Chronic obstructive pulmonary disease (COPD) is a relentlessly progressive disease, one of the 3 leading causes of deaths and morbidity worldwide [1]. COPD is projected to increase in the coming decades because of continued exposure to risk factors and aging [1,2]. The largest COPD burden is attributed to acute exacerbations (AE-COPD), characterized by sudden worsening of respiratory symptoms over ≤2 weeks [3]. Cigarette smoke, the main risk factor of COPD, causes inflammation and oxidative stress (OS) both in the airways and in the whole body [4]. OS is a key player in the development and progression of COPD [5]. Thus, a strategy to diagnose and prevent COPD via redox-inflammatory path is a critical priority. We currently concentrated on systemic effects of COPD and showed that DNA damage and its reparation increased in peripheral blood cells, along with the progression of the airflow obstruction. The damage was even more severe amongst patients with AE-COPD, showing the incredible burden COPD brings about in the whole body. We also showed that some enzymes that fight the inflammation were expressed higher in COPD patients’ bloodstream, whereas other enzymes that facilitate resolving the inflammation were under-expressed. This overactivation of the redox-inflammatory axis and the inability to resolve it provides a new explanation for the vicious cycle of the development and progression of COPD. However, the expressions of not all enzymes changed as the airflow limitation progressed, raising questions as to what might be the associates of lung function decline and development of COPD. Lastly, we found that synthetic antioxidants, new therapeutic potentials, despite increasing the level of certain antioxidant enzymes, also increased the expression of some pro-inflammatory enzymes. Therefore, these cannot possibly be used directly as themselves, but could serve as a lead for designing further COPD therapies
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