2nd Annual Meeting, March 17-19, 2016, Marriott Marquis, NYC
HVS Main Site
Annual Meeting Home
Final Program
Past & Future Meetings


Back to 2016 Annual Meeting Posters


Left ventricular overload is required for manifestation of overt cardiac phenotypes in SIRT6-deficient mice
Grace C. Verzosa, MD, Michael A. Hagler, BS, Carolyn M. Roos, MS, Bin Zhang, MD, Jordan D. Miller, Ph.D..
Mayo Clinic, Rochester, MN, USA.

OBJECTIVE: To determine whether the sex-dependent cardiac phenotypes in sirtuin 6-deficient mice are influenced by aging and/or calcific aortic stenosis.
METHODS: We studied two groups of mice. Group 1 was comprised of hyperlipidemic (Ldlr-/-ApoB100/100 ) mice that were either wild type (WT) or heterozygous (HET) for sirtuin 6. Mice were fed with Western diet (42%fat, 0.2%cholesterol) for 12 months. Group 2 was comprised of 18 month-old non-hyperlipidemic mice that were WT or HET for sirtuin 6 fed a regular chow diet. Two-dimensional and Doppler echocardiography were performed at 12-month time point. Left ventricular ejection fraction (EF), LV mass, and aortic valve cusp separation were measured.
RESULTS: Hypercholesterolemic mice developed aortic valve stenosis after 12 months of diet. Cusp separation distance was smaller in HET (WT =0.85 ± 0.02 mm, HET=0.75 ± 0.02 mm, P=0.002) and left ventricular mass was higher in female WT mice compared to HET littermates (WT = 118 ± 6.3 mm, HET=98 ± 8.8 mm, P=0.039). In contrast, aged mice did not develop aortic valve dysfunction, and left ventricular mass was comparable between genotypes (WT = 106±11 mg, HET = 100 ± 17.5 mg, P0.78). Furthermore, there was no significant difference in ejection fraction between WT and HET in the aged, normocholesterolemic mice.
CONCLUSIONS:
Chronic increases in ventricular afterload are essential for development of overt ventricular hypertrophy in aging mice. Furthermore, our data suggest that SIRT6 plays an integral, context-dependent role not only in the pathogenesis of hypercholesterolemia-induced valvular dysfunction, but also in modulating the hypertrophic responses to progressive increases in left ventricular afterload.


Back to 2016 Annual Meeting Posters