| 1. |
- Ahmed, Abdulla, et al.
(författare)
-
Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics
- 2020
-
Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:5, s. 2340-2353
-
Tidskriftsartikel (refereegranskat)abstract
- 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 (rs = 0.7; P < 0.0001), pulmonary arterial wedge pressure (rs = 0.73; P < 0.0001), pulmonary vascular resistance (rs = 0.65; P = 0.00062), and pulmonary arterial compliance (rs = -0.52; P = 0.0074). The change in plasma IGFBP7 after HT correlated with improved mean right atrial pressure (rs = 0.71; P = 0.00011) and N-terminal pro-brain natriuretic peptide (rs = 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.
|
|
| 2. |
- Ahmed, Abdulla, et al.
(författare)
-
Prolargin and matrix metalloproteinase-2 in heart failure after heart transplantation and their association with haemodynamics
- 2020
-
Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:1, s. 224-235
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: Remodelling of the extracellular matrix (ECM) is a key mechanism involved in the development and progression of heart failure (HF) but also functional in associated pulmonary hypertension (PH). Our aim was to identify plasma ECM proteins associated to end-stage HF and secondary PH in relation to haemodynamics, before and after heart transplantation (HT).METHODS AND RESULTS: Twenty ECM plasma proteins were analysed with proximity extension assay in 20 controls and 26 HF patients pre-HT and 1 year post-HT. Right heart catherization haemodynamics were assessed in the patients during the preoperative evaluation and at the 1 year follow-up post-HT. Plasma levels of prolargin and matrix metalloproteinase-2 (MMP-2) were elevated (P < 0.0001) in HF patients compared with controls and decreased (P < 0.0001) post-HT towards controls' levels. The decrease in prolargin post-HT correlated with improved mean right atrial pressure (rs = 0.63; P = 0.00091), stroke volume index (rs = -0.73; P < 0.0001), cardiac index (rs = -0.64; P = 0.00057), left ventricular stroke work index (rs = -0.49; P = 0.015), and N-terminal pro brain natriuretic peptide (rs = 0.7; P < 0.0001). The decrease in MMP-2 post-HT correlated with improved mean pulmonary artery pressure (rs = 0.58; P = 0.0025), mean right atrial pressure (rs = 0.56; P = 0.0046), pulmonary artery wedge pressure (rs = 0.48; P = 0.016), and N-terminal pro brain natriuretic peptide (rs = 0.56; P = 0.0029).CONCLUSIONS: The normalization pattern in HF patients of plasma prolargin and MMP-2 post-HT towards controls' levels and their associations with improved haemodynamics indicate that prolargin and MMP-2 may reflect, in part, the aberrant ECM remodelling involved in the pathophysiology of HF and associated PH. Their potential clinical use as biomarkers or targets for future therapy in HF and related PH remains to be investigated.
|
|
| 3. |
- Arvidsson, Mattias, et al.
(författare)
-
Plasma proteoglycan prolargin in diagnosis and differentiation of pulmonary arterial hypertension
- 2021
-
Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 8:2, s. 1230-1243
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Right ventricular dysfunction may arise because of pulmonary arterial hypertension (PAH). Development of new diagnostic methods able to identify PAH and allow for earlier treatment initiation, before the development of vascular remodelling and manifest right heart failure (HF), could potentially improve prognosis. Proteoglycans and inflammatory proteins are involved in vascular remodelling. We aimed to investigate their potential as biomarkers to differentiate PAH in a dyspnoeic population. Methods and results: Plasma from 152 patients with PAH (n = 48), chronic thrombo-embolic pulmonary hypertension (n = 20), pulmonary hypertension due to HF with reduced (n = 36) or preserved (n = 33) ejection fraction, and HF without pulmonary hypertension (n = 15) and 20 healthy controls were analysed with proximity extension assays. Haemodynamics were assessed in the patients with right heart catheterization. Plasma prolargin levels in PAH were lower compared with all the other studied disease groups (P < 0.001) but higher than the controls' levels (P = 0.003). Receiver operating characteristic curve of prolargin as a PAH-differentiating marker in a pooled population, encompassing all the other studied disease groups, had a sensitivity of 74% and a specificity of 83.3% (area under the curve = 0.84, P < 0.001). Prolargin correlated with the mean right atrial pressure (rs = 0.65, P < 0.001), N-terminal pro-brain natriuretic peptide (rs = 0.64, P < 0.001), cardiac index (rs = −0.31, P = 0.029), stroke volume index (rs = −0.41, P = 0.004), right ventricular stroke work index (rs = −0.31, P = 0.032), six-minute walking distance (rs = −0.41, P = 0.005), and mixed venous blood oxygen saturation (rs = −0.42, P = 0.003). Conclusions: Plasma prolargin levels differentiate PAH patients from controls and the other investigated dyspnoea groups including HF. Its potential in PAH differentiation may be enhanced by inclusion in a multi-marker panel. Larger studies are needed to evaluate its discriminative ability of PAH in relation to other dyspnoea aetiologies and its potential role in PAH risk stratification and pathobiology.
|
|
