Koudstaal, Thomas

English

Pulmonary hypertension (PH) is a debilitating disease characterized by structural remodeling ofthe arterial vasculature of the lung leading to increased vascular resistance and increased pulmonaryarterial pressures, right ventricular (RV) hypertrophy, heart failure and ultimately, death. Based on theunderlying causes of PH, the WHO classification system divides PH patients into 5 groups: (1) PulmonaryArterial Hypertension (PAH), (2) PH due to left heart disease, (3) PH due to lung disease, (4) ChronicThromboembolic PH (CTEPH), and (5) PH with unclear and/or multifactorial mechanisms.In pulmonary arterial hypertension (PAH) patients, vascular endothelial cell proliferation along withconcurrent formation of new blood vessels (neoangiogenesis), when exuberant, results in the formation ofglomeruloid structures in pulmonary arterioles known as the plexiform lesions. These plexiform lesionsare typically defined as dynamic networks of vascular channels formed by uncontrolled proliferation ofendothelial cells. Both PAH and CTEPH histology displays extensive accumulation of immune cells.IPAH patient lungs and lung biopsy material from CTEPH patients shows compelling evidence foractivation of the innate immune system. This includes pathological involvement of macrophages, mastcells (MCs) and neutrophils by production of inflammatory cytokines, recruitment of other immune cellsand local inflammation and damage. Lungs of IPAH patients demonstrate increased numbers of dendriticcells (DCs) , acting as a bridge between innate and the adaptive immune system by presentation ofantigens to T cells. DCs contribute to increased production of cytokines and chemokines, attracting otherinflammatory cells to the site of inflammation. Dysregulated Th17 immunity is another phenomenon inPAH patients, creating a pro-inflammatory auto-immune environment. Moreover, IPAH patients displayan increase of circulating autoantibodies specifically targeting endothelial cell surface antigens. Extensivebiomarker research reveals that many inflammatory and immune markers correlate with hemodynamicsand/or prognosis of PAH and CTEPH patients.Currently, there is still much unknown about the pathological involvement of the immune systemin PAH and CTEPH etiology. Novel insights are required, to gain knowledge into novel pathways fortherapeutic targets and new treatment options for researchers and clinicians. Therefore, the aims of thisthesis were to; (I) further unravel the immunological imbalance in pulmonary arterial hypertension(PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) pathogenesis, (II) to find novelbiomarkers and therapeutic targets<br/

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Dendritic cells and t cells in pulmonary hypertension:A dangerous infl ammatory symphony

https://pure.eur.nl/files/67792722/phd_thesis_thomas_koudstaal_633d3834c25c5.pdf

Dendritic cells and t cells in pulmonary hypertension:A dangerous infl ammatory symphony

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