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Canadian Journal of Cardiology

MITRAL VALVE CHORDAE TENDINEAE DEVELOP INDEPENDENTLY FROM LEAFLET TISSUE DURING FETAL DEVELOPMENT

      Background

      During fetal development of the mitral valve, chordae tendineae are thought to derive from the leaflet after it’s delamination from the ventricular wall. However, preliminary work on the fetal bovine heart has shown the presence of branched chordae tendineae well before leaflet delamination (Fig. 1A). We hypothesized that the fetal chordae and leaflet tissue are developing along distinct timelines in the bovine heart. To test this hypothesis, we examined the anatomical development and extracellular matrix composition of the bovine mitral valve chordae and leaflet during fetal development and in adult.

      Methods and Results

      Fetal bovine hearts were harvested from a local slaughterhouse and crown-rump length was used to determine gestational age. Samples ranged from 83-270 d.g. (full term = 290d.g.). Anterior leaflets were imaged then chordae number and leaflet area measured in ImageJ. Immature and mature collagen contents were determined using Sircol™ Soluble and Insoluble Collagen assays (Biocolour, Carrickfergus, UK). Age-paired tissue samples underwent Blyscan Sulfated Glycosaminoglycan (sGAG) assays (Biocolour) to determine sGAG content. Both chordae tendineae number and leaflet area increased linearly during gestation. While leaflet area continued to increase into adulthood the chordae number remained unchanged after birth. Mature, insoluble collagen content increased during gestation in both chordae and leaflet, with the rate of increase higher in the leaflet than chordae (ANCOVA p = 2.07e-5, Fig 1C). Despite this, average levels of mature collagen remained higher in chordae during gestation, with contents in the leaflet more than doubling post-natally (Fig 1D). Surprisingly, there was no change in the content of immature, uncrosslinked collagen during gestation in either tissue (Fig. 1E). Immature collagen was found at nearly 10-fold higher concentrations in fetal chordae than in leaflet, where low levels remained unchanged into adulthood (Fig. 1F). Unlike collagen, GAG content was similar in both tissues and remained unchanged during gestation and postnatal development.