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Gap Junction Formation in Heart Valves in Response to Mechanical Loading

Valvular interstitial cells (VICs) are responsible for the maintenance of heart
valve leaflet structure, however their responses to mechanical loading are not fully
understood. Further characterization of VIC responses with regards to phenotype
(quiescent or activated via ?-smooth muscle actin [?-SMA]) and communication (through
gap junction proteins connexins 43 and 26) were studied. Tissue strips from porcine
aortic, pulmonary, and mitral valves were cyclically stretched in the circumferential
direction at normal and above normal membrane tensions for 48 hours at 1 Hz, 37°C, and
5% CO2. Unloaded tissues were statically incubated concurrently with loaded tissues, and
fresh tissue controls were collected immediately. VIC phenotype was identified by ?-
SMA via immunohistochemical staining and cell enumeration, as well as by gene
expression via RT-PCR. Gap junction protein Cx43 was also evaluated via
immunohistochemical staining and cell enumeration and by gene expression via RT-PCR,
whereas Cx26 was evaluated using immunohistochemical staining and cell enumeration
only. Within the range tested, it was found that mechanical loading did not affect ?-SMA
or gap junction protein levels, nor were any differences in responses noted between valve
types. However, the ?-SMA gene expression level was significantly lower in the mitral
valve compared to the aortic and pulmonary valves. This may indicate a difference in the
genetic response pathways among the valves, but not in the functional outcomes. This
difference may be explained by embryological origins, since the mitral valve, unlike the
aortic and pulmonary valves, contains only VICs and no neural crest cells.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:NSHD.ca#10222/36260
Date28 June 2013
CreatorsO'Malley, Karen L.
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish

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