Abstract
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 (rs = 0.65, p = 0.00049), Δpulmonary artery wedge pressure (rs = 0.72, p < 0.0001), Δpulmonary arterial compliance (PAC) (rs = − 0.52, p = 0.0083) and Δpulmonary vascular resistance (PVR) (rs = 0.58, p = 0.0032). ΔHER4 correlated with Δmean right atrial pressure (rs = 0.51, p = 0.012), ΔNT-proBNP (rs = 0.48, p = 0.016) and Δcardiac index (rs = − 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.
Highlights
Heart failure (HF), a global pandemic present in 1–2% of the adult population, is caused by pathological changes in structural and/or functional properties of the cardiomyocytes, Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, SwedenThe Haemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO
Plasma stem cell factor (SCF) were, low in HF patients in Receptor tyrosine kinases (RTKs) signalling regulates diverse cellular functions through activation of the downstream mitogen-activated protein kinases, of which ERK1/2, ERK5 and JNK are pivotal in cardiac development, hypertrophy as well as in both physiological and pathophysiologic cardiac remodelling [3]
Among the 28 RTKs and related proteins, plasma vascular endothelial growth factor-D (VEGF-D) and human epidermal growth factor-4 (HER4) were elevated in severe HF patients compared to controls
Summary
The Haemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO. PH due to left heart disease (LHD) is mainly induced by left HF, congenital or valvular heart diseases and if sustained may lead to endothelial dysfunction, followed by excessive vasoconstriction and pulmonary vascular remodelling [5,6,7]. Such PH may advance into a “fixed” phenotype, harbouring stiff vessels unresponsive to pulmonary vasodilators, potentially imposing a relative contraindication for heart transplantation (HT) [7,8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
