Vitamin A deficiency attenuates cardiac rupture in Stra6-deficient hearts following ischemic injury

BACKGROUND: Stimulated by retinoic acid gene 6 (STRA6) is a cell surface receptor that regulates cellular uptake of vitamin A metabolites and cardiac development. We hypothesized that Stra6 expression attenuates ischemic injury-induced heart failure following myocardial infarction (MI) by vitamin A-dependent mechanisms. METHODS: MI was induced in mice with Stra6 germline deletion, vitamin A deficiency (VitAD) by combined lecithin-retinol acyltransferase (Lrat) germline deletion and feeding with a vitamin A-deficient diet. Contractile function was determined by transthoracic echocardiography, cardiac structure was assessed by histological analysis, and gene profiling was performed by RNA sequencing. RESULTS: Stra6 deletion and VitAD did not impact contractile function and cardiac structure under basal conditions. Stra6 deficiency resulted in myocardial rupture, with the majority of mice dying by 4 days post-MI, which additional VitAD attenuated. Interestingly, contractile function, mRNA expression of heart failure markers, and cardiac structure were not different between groups 3 days post-MI. Gene profiling 3 days post-MI revealed decreased Wnt signaling in Stra6-deficient relative to wildtype hearts, which was reversed by VitAD. CONCLUSION: The present study identifies an unexpected role for VitAD, which preserves Wnt signaling and attenuates cardiac rupture in Stra6-deficient hearts following ischemic injury.

• Smolenski, Y.
• Froese, N.
• Galuppo, P.
• Werlein, C.
• Gigina, A.
• Talbot, S. R.
• Erschow, S.
• Wedekind, D.
• Geffers, R.
• Ghyselinck, N. B.
• Bähre, H.
• Kamp, J. C.
• Neubert, L.
• Ricke-Hoch, M.
• Bauersachs, J.
• Riehle, C.