Rhea Hurnik

1^ST Class Honours - Earth Sciences / Biology
Michael J. Keen Memorial Award - 2011

Human natriuretic peptides (NPs), including ANP, BNP and CNP, regulate many important processes in the body including blood pressure control, bone homeostasis, and protection against cardiac hypertrophy and cardiac fibrosis. Natriuretic peptides mediate their effects through three receptors, NPR-A, NPR-B and NPR-C. While the natriuretic peptide-mediated effects of NPR-A and NPR-B have been well characterized, NPR-C is poorly understood. It was initially thought to function as a ‘clearance receptor’ with no signaling function; however, numerous studies have demonstrated NPR-C actually activates inhibitory G proteins (GI) Data from the Rose laboratory demonstrates that mice lacking functional NPR-C receptors (NPR-C^-/-) exhibit SAN dysfunction, slowed atrial conduction, and increased susceptibility to atrial fibrillation. A possible mechanism for these conditions could be fibrotic remodeling in the heart of the NPR-C^-/- mouse.

Accordingly, the purpose of this project was to assess the patterns of collagen deposition in hearts of NPR-C^-/- mice using histological techniques. It was hypothesized that there would be an increase in interstitial collagen in the atria of NPR-C^-/- mice when compared to wild type littermates. The atrial appendages of 5 NPR-C^-/- and 5 wild type littermates, and the whole heart of 1 NPR-C^-/- and 1 wild type littermate were surgically removed, sectioned and stained with picrosirus red and fast green solution. This solution stains collagen red and cell cytoplasm green. The percent area of collagen was calculated using digital images of the tissue and ImageJ software.

NPR-C^-/- mice showed increased levels of interstitial collagen compared to wild type littermates in the right (P< 0.001) and left (P<0.008) atrial appendages of the heart. Patterns of collagen deposition were also measured in the left ventricles of wildtype and NPR-C^-/- mice. This preliminary data demonstrate that there was no difference in the amount of interstitial collagen in the ventricles of the NPR-C^-/- mouse. Increased interstitial collagen in the atrial appendages of the NPR-C^-/- mice suggests that fibrotic remodeling is a likely mechanism for the SAN dysfunction, slowed atrial conduction and increased susceptibility to atrial fibrillation. Normal levels of interstitial collagen in the ventricles of the NPR-C^-/- mouse suggest that fibrotic remodeling is limited to the atrial appendages of the heart in NPR-C^-/- mice.

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Pages: 36
Supervisor: Robert Rose