Prolargin and matrix metalloproteinase‐2 in heart failure after heart transplantation and their association with haemodynamics

Aims Metabolic derangement is implicated in the pathophysiology of heart failure (HF) and pulmonary hypertension (PH). We aimed to identify the dynamics of metabolic plasma proteins linked to end-stage HF and associated PH in relation to haemodynamics, before and after heart transplantation (HT). Methods and results Twenty-one metabolic plasma proteins were analysed with proximity extension assay in 20 controls and 26 patients before and 1 year after HT. Right heart catheterizations were performed in the HF patients pre-operatively and 1 year after HT. Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and insulin-like growth factor-binding protein 7 (IGFBP7) were higher in HF patients compared with controls (P < 0.0001) and decreased after HT (P < 0.0001), matching controls' levels. The decrease in sRAGE after HT correlated with improved mean pulmonary arterial pressure (r s = 0.7; P < 0.0001), pulmonary arterial wedge pressure (r s = 0.73; P < 0.0001), pulmonary vascular resistance (r s = 0.65; P = 0.00062), and pulmonary arterial compliance (r s = À0.52; P = 0.0074). The change in plasma IGFBP7 after HT correlated with improved mean right atrial pressure (r s = 0.71; P = 0.00011) and N-terminal pro-brain natriuretic peptide (r s = 0.71; P < 0.0001). Conclusions Our results indicate that plasma sRAGE may reflect passive pulmonary vascular congestion and the 'mechanical' state of the pulmonary vasculature in HF patients with or without related PH. Furthermore, sRAGE and IGFBP7 may provide additional insight into the pathophysiological mechanisms in HF and associated PH. Their potential clinical and therapeutic relevance in HF and associated PH need further investigation.

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“…The characteristics of the controls and heart transplant recipients have previously been described ( Table 1 ). 13,18 …”

Section: Resultsmentioning

confidence: 99%

Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics

Ahmed

Arvidsson

et al. 2020

ESC Heart Failure

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“…A missing CO value was calculated by indirect Fick instead of thermodilution before HT. Parts of this table have been previously published [ 21 ]…”

Section: Methodsmentioning

confidence: 99%

“…Informed written consent was acquired from all participants. The population has previously been characterized, including patients' plasma creatinine and NT-proBNP, shown in Table 1 [20,21]. Briefly, 50% of the controls were male, had a median age of 41 years and a median body surface area (BSA) of (1.92 m 2 , n = 19).…”

Section: Study Populationmentioning

confidence: 99%

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Elevated plasma endocan and BOC in heart failure patients decrease after heart transplantation in association with improved hemodynamics

Ahmed

Bouzina

et al. 2020

Heart Vessels

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Background The prevalence of heart failure (HF) is rising with ageing population and constitutes a major health problem globally. A common complication of HF is pulmonary hypertension (PH) which negatively impacts survival. A pathophysiological association between HF and PH with tumorigenic processes has been suggested. We aimed to identify the plasma levels of, and the association between tumour-related proteins and hemodynamic improvements in patients with HF and PH due to left heart disease (LHD) before and 1-year after heart transplantation (HT). Methods Forty-eight tumour-related proteins were measured with proximity extension assay in plasma from 20 controls and 26 HF patients before and 1-year after HT. Patients’ hemodynamics were measured with right heart catheterization. Results Out of 48 proteins, specifically, plasma levels of endocan and brother of CDO (BOC) were elevated in end-stage HF patients compared to controls (p < 0.001), but decreased after HT (p < 0.01), towards controls’ levels. The decrease of endocan levels after HT correlated with improved mean pulmonary arterial pressure (rs = 0.80, p < 0.0001), pulmonary arterial wedge pressure (rs = 0.63, p = 0.0012), and pulmonary vascular resistance (rs = 0.70, p < 0.001). The decrease and normalization of BOC after HT correlated with decreased mean right atrial pressure (rs = 0.61 p = 0.0015) and NT-proBNP (rs = 0.57, p = 0.0022), as well as increased cardiac index (rs = − 0.51, p = 0.0086) and left-ventricular stroke work index (rs = − 0.57, p = 0.0039). Conclusion Our results suggest that (i) plasma endocan in HF may reflect the state of pulmonary vascular congestion and PH-LHD, whereas (ii) plasma BOC may reflect the cardiac function and the hemodynamic overload in HF. The exact role of these proteins and their clinical applicability as biomarkers in HF and PH-LHD ought to be investigated in larger cohorts.

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“…Patients' characteristics before and 1-year after HT are shown in Table 1 as previously described [22]. Among the 26 included patients, three (11.5%) had diabetes mellitus, five (19%) had hypertension and 14 (54%) had a history of atrial fibrillation before HT.…”

Section: Patients' Characteristicsmentioning

confidence: 99%

Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics

Ahmed

Säleby

et al. 2020

Heart Vessels

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Receptor tyrosine kinases (RTKs) are implicated in cardiovascular growth and remodelling. We aimed to identify the plasma levels of RTKs and related proteins and their association with haemodynamic alterations in heart failure (HF) and related pulmonary hypertension (PH) following heart transplantation (HT). Using proximity extension assay, 28 RTKs and related proteins were analysed in plasma from 20 healthy controls and 26 HF patients before and 1-year after HT. In end-stage HF, out of 28 RTKs, plasma vascular endothelial growth factor-D (VEGF-D) and human epidermal growth factor-4 (HER4) were elevated compared to controls (p < 0.001), but decreased (p < 0.0001) and normalised after HT. Following HT, plasma changes (Δ) of VEGF-D correlated with Δmean pulmonary artery pressure (r s = 0.65, p = 0.00049), Δpulmonary artery wedge pressure (r s = 0.72, p < 0.0001), Δpulmonary arterial compliance (PAC) (r s = − 0.52, p = 0.0083) and Δpulmonary vascular resistance (PVR) (r s = 0.58, p = 0.0032). ΔHER4 correlated with Δmean right atrial pressure (r s = 0.51, p = 0.012), ΔNT-proBNP (r s = 0.48, p = 0.016) and Δcardiac index (r s = − 0.56, p = 0.0044). In HF patients following HT, normalisation of VEGF-D reflected reversal of passive pulmonary congestion and restored PAC and PVR; whereas the normalisation of HER4 reflected decreased volume overload and improved cardiac function. The precise function of these proteins, their potential clinical use and pathophysiological relation in HF and related PH remain to be elucidated.

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Prolargin and matrix metalloproteinase‐2 in heart failure after heart transplantation and their association with haemodynamics

Cited by 11 publications

References 55 publications

Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics

Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics

Elevated plasma endocan and BOC in heart failure patients decrease after heart transplantation in association with improved hemodynamics

Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics

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