title: High levels of zinc-protoporphyrin identify iron metabolic abnormalities in pulmonary arterial hypertension.
abstract: Iron homeostasis influences the development of pulmonary arterial hypertension (PAH) associated with hypoxia or hematologic disorders. To investigate whether severity of idiopathic PAH (IPAH) is impacted by alterations in iron metabolism, we assessed iron metabolic markers, including levels of zinc-protoporphyrin (Zn-pp), transferrin receptor, and red blood cell numbers and morphology in IPAH, associated PAH and sleep apnea-induced pulmonary hypertension patients in comparison to healthy controls and asthmatics. Despite similarly normal measures of iron metabolism, Zn-pp levels in IPAH and sleep apnea patients were elevated approximately twofold, indicating deficient iron incorporation to form heme and levels were closely related to measures of disease severity. Consistent with high Zn-pp, PAH patients had increased red cell distribution width (RDW). In an expanded cohort including patients with IPAH and familial disease, the RDW was validated and related to clinical parameters of severity; including pulmonary artery pressures and 6-minute walk distances. These results reveal an increased prevalence of subclinical functional iron deficiency in primary forms of PAH that is quantitatively related to disease severity. This suggests that altered iron homeostasis influences disease progression and demonstrates the importance of closely monitoring iron status in PAH patients.
authors: Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
authors: Ilka
authors: I
authors: Decker
authors: Sudakshina
authors: S
authors: Ghosh
authors: Suzy A
authors: SA
authors: Comhair
authors: Samar
authors: S
authors: Farha
authors: Wai Hong Wilson
authors: WH
authors: Tang
authors: Margaret
authors: M
authors: Park
authors: Sihe
authors: S
authors: Wang
authors: Alan E
authors: AE
authors: Lichtin
authors: Serpil C
authors: SC
authors: Erzurum
mesh_terms: D000328:Adult; D001772:Blood Cell Count; D001773:Blood Cells / Q000378:metabolism; D015331:Cohort Studies; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011524:Protoporphyrins / Q000097:blood*; D012720:Severity of Illness Index; D012891:Sleep Apnea Syndromes / Q000097:blood / Q000378:metabolism
chemical_list: D011524:Protoporphyrins; C017803:zinc protoporphyrin; D007501:Iron