Figure 6.

Perturbation of filamin-A–serotonin interactions blunt matrix remodelling. (A) Serotonin significantly increased the ability for valve fibroblasts to condense collagen over a 5-day period. Actual gels are represented in (A) to demonstrate effect of exogenous addition of Serotonin. (B and C) Serotonin-induced compaction (in the presence of 100 µM serotonin) was blunted using a SERT inhibitor (clomiprimine) and a TG inhibitor (cystamine), demonstrating internalized serotonin and TG activity are required for matrix condensation. (A/Ao, final area of gel divided by initial area). *Statistical significance: P < 0.05. ns, not significant. n > 12 for each condition. (D) E17.5 anterior mitral leaflets were removed from cKO and littermate WT mice placed in fibrin compaction assays in the presence of serotonin. Filamin-A cKO cells exhibit ∼20% reduced ability to efficiently compact the matrix (compare left panels to right panels) in the presence of 100 μM serotonin with P-values denoted. n = 20 constructs analysed for each genotype.