Am J Physiol Regul Integr Comp Physiol. 2023 Dec 4. doi: 10.1152/ajpregu.00164.2023. Online ahead of print.
ABSTRACT
Down syndrome (Ds) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of Ds, to quantify heart structure and function with echocardiography in 18-month male Ts65Dn and WT mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of Ds. The left ventricle was smaller in Ts65Dn vs WT, as well as the anterior wall thickness of the left ventricle during both diastole (LVAW_d; mm) and systole (LVAW_s; mm) as assessed by echocardiography. Other functional metrics were similar between groups including left ventricular area end-systole (mm2), left ventricular area end-diastole (mm2), left ventricular diameter end-systole (mm), left ventricular diameter end-diastole (mm), isovolumetric relaxation time (ms), mitral valve atrial peak velocity (mm/s), mitral valve early peak velocity (mm/s), ratio of atrial and early peak velocities (E/A), heart rate (bpm), ejection fraction (%), and fractional shortening (%). Nicotinamide phosphoribosyltransferase (NAMPT) protein expression, NAD concentration, and tissue weight were lower in the left ventricle of Ts65Dn vs. WT mice. Sirtuin 3 (SIRT3) protein expression and citrate synthase activity were not different between groups. Although cardiac function was generally preserved in male Ts65Dn, the altered heart size and bioenergetic disturbances may contribute to differences in aging for Ds.
PMID:38047317 | DOI:10.1152/ajpregu.00164.2023
