Endothelitis profile in acute heart failure and cardiogenic shock patients: Endocan as a potential novel biomarker and putative therapeutic target

Autores da FMUP

• Marta Fernanda Reina Couto

  Autor

• Janete Maria Quelhas Dos Santos

  Autor

• Maria Paula De Valadares Souto Pinto Serrão

  Autor

• Claudia Camila Rodrigues Pereira Dias

  Autor

• João Tiago De Sousa Pinto Guimarães

  Autor

• Roberto Liberal Fernandes Roncon Albuquerque

  Autor

• José Artur Osório De Carvalho Paiva

  Autor

• Teresa Maria De Jesus Teixeira De Sousa

  Autor

Participantes de fora da FMUP

• Silva Pereira, C
• Pereira Terra, P
• Bessa, J
• Afonso, J
• Martins, S
• Morato, M.
• Albino Teixeira, A

Unidades de investigação

• Biomedicina

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Medicina

• Recursos Comuns

  

  Investigador

  Guilhermina Maria Da Silva Rêgo

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Aims: Inflammation-driven endothelitis seems to be a hallmark of acute heart failure (AHF) and cardiogenic shock (CS). Endocan, a soluble proteoglycan secreted by the activated endothelium, contributes to inflammation and endothelial dysfunction, but has been scarcely explored in human AHF. We aimed to evaluate serum (S-Endocan) and urinary endocan (U-Endocan) profiles in AHF and CS patients and to correlate them with biomarkers/parameters of inflammation, endothelial activation, cardiovascular dysfunction and prognosis. Methods: Blood and spot urine were collected from patients with AHF (n = 23) or CS (n = 25) at days 1-2 (admission), 3-4 and 5-8 and from controls (blood donors, n = 22) at a single time point. S-Endocan, U-Endocan, serum IL-1 beta, IL-6, tumour necrosis factor-alpha (S-TNF-alpha), intercellular adhesion molecule-1 (S-ICAM-1), vascular cell adhesion molecule-1 (S-VCAM-1) and E-selectin were determined by ELISA or multiplex immunoassays. Serum C-reactive protein (S-CRP), plasma B-type natriuretic peptide (P-BNP) and high-sensitivity troponin I (P-hs-trop I), lactate, urea, creatinine and urinary proteins, as well as prognostic scores (APACHE II, SAPS II) and echocardiographic left ventricular ejection fraction (LVEF) were also evaluated. Results: Admission S-Endocan was higher in both patient groups, with CS presenting greater values than AHF (AHF and CS vs. Controls, p < 0.001; CS vs. AHF, p < 0.01). Admission U-Endocan was only higher in CS patients (p < 0.01 vs. Controls). At admission, S-VCAM-1, S-IL-6 and S-TNF-alpha were also higher in both patient groups but there were no differences in S-E-selectin and S-IL-1 beta among the groups, nor in P-BNP, S-CRP or renal function between AHF and CS. Neither endocan nor other endothelial and inflammatory markers were reduced during hospitalization (p > 0.05). S-Endocan positively correlated with S-VCAM-1, S-IL-6, S-CRP, APACHE II and SAPS II scores and was positively associated with P-BNP in multivariate analyses. Admission S-Endocan raised in line with LVEF impairment (p = 0.008 for linear trend). Conclusion: Admission endocan significantly increases across AHF spectrum. The lack of reduction in endothelial and inflammatory markers throughout hospitalization suggests a perpetuation of endothelial dysfunction and inflammation. S-Endocan appears to be a biomarker of endothelitis and a putative therapeutic target in AHF and CS, given its association with LVEF impairment and P-BNP and its positive correlation with prognostic scores.

Keywords

• endocan; endothelitis; acute heart failure; cardiogenic shock; biomarker