The Impact of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor on Cardiac Fibroblasts Grown under Altered Gravity Conditions

Abstract

Background: Myocardium is very sensitive to gravitational changes. During a spaceflight cardiovascular atrophy paired with rhythm problems and orthostatic intolerance can occur. The aim of this study was to investigate the impact of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on cardiac fibroblasts (CF) grown under altered gravity conditions. Methods: We examined the influence of exposure to a Random Positioning Machine (RPM) on CF, derived from porcine hearts. We focused on growth, extracellular matrix protein (ECMP) synthesis and apoptosis. Results: When cultured on a RPM, CF began to form 3D spheroids within 24h, irrespective of growth factor treatment. Exposure to RPM induced an increased synthesis of ECMP and also resulted in elevated apoptosis in adherent CF as measured by terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling (TUNEL) analysis, 4',6-diamidino-2-phenylindole (DAPI) staining, and caspase-3 detection. bFGF and VEGF significantly decreased the amount of ECMP (collagen type I, III, chondroitin sulfate) in 1g and RPM cultures, and also significantly reduced the amount of apoptotic CF as well as caspase-3. Conclusions: Altered gravity conditions on a RPM induced 3D growth, elevated ECMP synthesis and apoptosis in cardiac fibroblasts. Growth factor treatment attenuated programmed cell death and ECMP secretion.

Morphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity

“…It is also a cell adhesion molecule and it became apparent that laminin is a gravi-sensitive protein. Changes in the amount of laminin in MCS had also been detected in earlier studies investigating cardiac fibroblasts, follicular thyroid cancer cells or endothelial cells after RPM-exposure 22,33,34 . These results are cell type-specific.…”

A comparison of left and right atrial fibroblasts reveals different collagen production activity and stress‐induced mitogen‐activated protein kinase signalling in rats

“…VEGF has also been shown to exert an antifibrotic effect by attenuating the collagen production capability of cardiac fibroblasts, and by inhibiting myofibroblast transformation in a kidney cortex cell line (Ulbrich et al . , Hong et al . ).…”

Role of Apoptosis in Wound Healing and Apoptosis Alterations in Microgravity

“…Another study focused on the effects of an RPM-exposure on porcine cardiac fibroblasts which exhibited an increase in apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling (TUNEL) analysis, 4 ′ , 6-diamidino-2-phenylindole (DAPI) staining, and caspase-3 detection (Ulbrich et al, 2010). Vascular Endothelial Growth factor (VEGF) and basic fibroblast growth factor (bFGF) application attenuated the number of apoptotic fibroblasts.…”