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Plasma insulin-like growth factor binding protein 1 in pulmonary arterial hypertension

Bouzina, Habib LU ; Hesselstrand, Roger LU and Rådegran, Göran LU (2020) In Scandinavian Cardiovascular Journal
Abstract

Background: Beside the pulmonary vasoconstriction observed in pulmonary arterial hypertension (PAH), severe proliferative and antiapoptotic cellular phenotypes result in vascular remodelling. Many recent findings indicate similarities between PAH and tumour pathology. For instance, insulin-like growth factor (IGF)-1 signalling, which is known to promote tumour development, is implicated in PAH. Higher circulating IGF binding protein (IGFBP)-1 levels are associated with worse survival in PAH. The present study aimed to investigate the relationship between plasma levels of various tumour-related biomarkers and PAH. Methods: IGFBP-1, -2 and -7, along with other tumour-related biomarkers, were measured in plasma from 48 treatment-naïve PAH... (More)

Background: Beside the pulmonary vasoconstriction observed in pulmonary arterial hypertension (PAH), severe proliferative and antiapoptotic cellular phenotypes result in vascular remodelling. Many recent findings indicate similarities between PAH and tumour pathology. For instance, insulin-like growth factor (IGF)-1 signalling, which is known to promote tumour development, is implicated in PAH. Higher circulating IGF binding protein (IGFBP)-1 levels are associated with worse survival in PAH. The present study aimed to investigate the relationship between plasma levels of various tumour-related biomarkers and PAH. Methods: IGFBP-1, -2 and -7, along with other tumour-related biomarkers, were measured in plasma from 48 treatment-naïve PAH patients and 16 healthy controls, using proximity extension assays. Among the PAH patients, 33 were also studied at an early treatment follow-up. Results: Plasma IGFBP-1 (p <.003), IGFBP-2 (p <.001), IGFBP-7 (p <.008), vimentin (p <.001), carbonic anhydrase 9 (p <.001), S100A11 (p <.001), human epididymis protein 4 (p <.001) and folate receptor-α (p <.004) were elevated in PAH, compared to controls. IGFBP-1 exhibited the most interesting correlations to clinical parameters and was selected for further analyses. IGFBP-1 correlated specifically to N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (r = 0.44, p <.002), mean right atrial pressure (r = 0.41, p <.004), venous oxygen saturation (r = –0.43, p <.003), cardiac index (r = –0.32, p <.03) and 6-minute walking distance (r = –0.29, p <.05). Plasma IGFBP-1 also correlated to risk scores based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) PAH guidelines (r = 0.43, p <.003) and the REVEAL model (r = 0.46, p <.001). PAH patients with supra-median baseline IGFBP-1 levels showed a trend for worse overall survival than those with infra-median levels (p =.087). IGFBP-1 was unaltered between baseline and an early treatment follow-up. However, IGFBP-1 changes, between baseline and follow-up, correlated to changes in NT-proBNP (r = 0.48, p <.006). Conclusion: Plasma IGFBP-1 levels at PAH diagnosis show moderate association to NT-proBNP and hemodynamics as well as with ESC/ERS and REVEAL risk scores.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
IGFBP, Plasma biomarkers, pulmonary arterial hypertension, risk assessment, tumour biology
in
Scandinavian Cardiovascular Journal
publisher
Taylor & Francis
external identifiers
  • pmid:32597241
  • scopus:85087549598
ISSN
1401-7431
DOI
10.1080/14017431.2020.1782977
language
English
LU publication?
yes
id
e3dfec3b-00ad-4dd2-8948-492266f2c8b4
date added to LUP
2020-07-17 09:56:57
date last changed
2021-02-23 01:46:42
@article{e3dfec3b-00ad-4dd2-8948-492266f2c8b4,
  abstract     = {<p>Background: Beside the pulmonary vasoconstriction observed in pulmonary arterial hypertension (PAH), severe proliferative and antiapoptotic cellular phenotypes result in vascular remodelling. Many recent findings indicate similarities between PAH and tumour pathology. For instance, insulin-like growth factor (IGF)-1 signalling, which is known to promote tumour development, is implicated in PAH. Higher circulating IGF binding protein (IGFBP)-1 levels are associated with worse survival in PAH. The present study aimed to investigate the relationship between plasma levels of various tumour-related biomarkers and PAH. Methods: IGFBP-1, -2 and -7, along with other tumour-related biomarkers, were measured in plasma from 48 treatment-naïve PAH patients and 16 healthy controls, using proximity extension assays. Among the PAH patients, 33 were also studied at an early treatment follow-up. Results: Plasma IGFBP-1 (p &lt;.003), IGFBP-2 (p &lt;.001), IGFBP-7 (p &lt;.008), vimentin (p &lt;.001), carbonic anhydrase 9 (p &lt;.001), S100A11 (p &lt;.001), human epididymis protein 4 (p &lt;.001) and folate receptor-α (p &lt;.004) were elevated in PAH, compared to controls. IGFBP-1 exhibited the most interesting correlations to clinical parameters and was selected for further analyses. IGFBP-1 correlated specifically to N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (r = 0.44, p &lt;.002), mean right atrial pressure (r = 0.41, p &lt;.004), venous oxygen saturation (r = –0.43, p &lt;.003), cardiac index (r = –0.32, p &lt;.03) and 6-minute walking distance (r = –0.29, p &lt;.05). Plasma IGFBP-1 also correlated to risk scores based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) PAH guidelines (r = 0.43, p &lt;.003) and the REVEAL model (r = 0.46, p &lt;.001). PAH patients with supra-median baseline IGFBP-1 levels showed a trend for worse overall survival than those with infra-median levels (p =.087). IGFBP-1 was unaltered between baseline and an early treatment follow-up. However, IGFBP-1 changes, between baseline and follow-up, correlated to changes in NT-proBNP (r = 0.48, p &lt;.006). Conclusion: Plasma IGFBP-1 levels at PAH diagnosis show moderate association to NT-proBNP and hemodynamics as well as with ESC/ERS and REVEAL risk scores.</p>},
  author       = {Bouzina, Habib and Hesselstrand, Roger and Rådegran, Göran},
  issn         = {1401-7431},
  language     = {eng},
  month        = {06},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Cardiovascular Journal},
  title        = {Plasma insulin-like growth factor binding protein 1 in pulmonary arterial hypertension},
  url          = {http://dx.doi.org/10.1080/14017431.2020.1782977},
  doi          = {10.1080/14017431.2020.1782977},
  year         = {2020},
}