Considering vasoprotective and anti-atherosclerotic activity of NO-sGC and COX-2-PGI2 pathways, it is tempting to speculate that these compensatory changes within coronary circulation could mitigate the development of symptomatic ischaemic heart disease in female ApoE/LDLR−/− mice and explain why their cardiac function was not compromised (Fig. 6) despite extensive coronary atherosclerosis at the age of 6–8 months (Fig. 5G–I). Here, APOE is linked to coronary atherosclerosis.