Characterization of Sex Differences in Aortic Valve Disease in Mice

Aortic valve disease has recently been shown to have sex-specific pathobiology, where female valves experience more fibrosis and less calcification than male valves despite similar levels of stenosis. To investigate whether these differences were mirrored in a mouse model, six-week old male and female Ldlr-/-;ApoB100/100 mice were fed high fat diet to induce valve disease. After four or eight months on diet, blood lipid and sex hormone levels were measured, valve function was assessed by echocardiography, and valve leaflet tissues were analyzed (immuno)histochemically and by polarized light microscopy to assess valve morphology and content. Males on high fat diet for eight months had more valvular dysfunction than females on diet, however male and female valve leaflets did not differ in size, thickness, or collagen content. However, polarized microscopy indicated more collagen remodelling in the base of the male leaflets compared to females, which could affect healthy valve mechanics. This study provides the first characterization of sex differences in a mouse model and sex-specific structural differences that relate to level of valve dysfunction.M.A.S

Environmental epidemiology of Kawasaki disease: Linking disease etiology, pathogenesis and global distribution.

The pathogenesis of Kawasaki disease (KD) is commonly ascribed to an exaggerated immunologic response to an unidentified environmental or infectious trigger in susceptible children. A comprehensive framework linking epidemiological data and global distribution of KD has not yet been proposed.Patients with KD (n = 81) were enrolled within 6 weeks of diagnosis along with control subjects (n = 87). All completed an extensive epidemiological questionnaire. Geographic localization software characterized the subjects' neighborhood. KD incidence was compared to atmospheric biological particles counts and winds patterns. These data were used to create a comprehensive risk framework for KD, which we tested against published data on the global distribution. Compared to controls, patients with KD were more likely to be of Asian ancestry and were more likely to live in an environment with low exposure to environmental allergens. Higher atmospheric counts of biological particles other than fungus/spores were associated with a temporal reduction in incidence of KD. Finally, westerly winds were associated with increased fungal particles in the atmosphere and increased incidence of KD over the Greater Toronto Area. Our proposed framework was able to explain approximately 80% of the variation in the global distribution of KD. The main limitations of the study are that the majority of data used in this study are limited to the Canadian context and our proposed disease framework is theoretical and circumstantial rather than the result of a single simulation.Our proposed etiologic framework incorporates the 1) proportion of population that are genetically susceptible; 2) modulation of risk, determined by habitual exposure to environmental allergens, seasonal variations of atmospheric biological particles and contact with infectious diseases; and 3) exposure to the putative trigger. Future modelling of individual risk and global distribution will be strengthened by taking into consideration all of these non-traditional elements

Composite analysis of wind patterns for months with high and low Kawasaki disease (KD) occurrences.

<p>Time series of standardized monthly number of KD cases, with months (May-October in grey) and anomalously high and low occurrences of new KD cases highlighted in red and blue, respectively (A). Wind speed (color, units [m/s]) and direction (arrows) during months with high KD occurrences (B), low KD occurrences (D) and difference between months with high and low KD occurrences (C) centered over the Pacific Ocean.</p

Conceptual framework for individual risk of developing Kawasaki disease (KD) linking disease etiology, pathogenesis and global distribution.

<p>Conceptual framework for individual risk of developing Kawasaki disease (KD) linking disease etiology, pathogenesis and global distribution.</p

Habitual environmental exposures in children with Kawasaki disease (KD).

<p>Habitual environmental exposures in children with Kawasaki disease (KD).</p

Clinical signs and symptoms in the weeks preceding the onset of Kawasaki disease (KD).

<p>Clinical signs and symptoms in the weeks preceding the onset of Kawasaki disease (KD).</p

Time series (5-day moving averages) and cross-correlation of new cases of Kawasaki disease (KD) vs. count of biological atmospheric particles for lag-times of 0 to 25 days for spores and fungi (ascomycetes, basidiomycetes and fungi imperfecti separately).

<p>Upward triangles indicate maximum and downward triangles minimum cross-correlations. The difference between lowest and peak correlation was statistically significant only for ascomycetes but the overall patterns was conserved for all types.</p

Questionnaire elements for case-control study.

<p>Questionnaire elements for case-control study.</p

Distribution of ethnicity/origin across controls and patients with Kawasaki disease (KD).

<p>Distribution of ethnicity/origin across controls and patients with Kawasaki disease (KD).</p