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). The gene discussed is APOE; the disease is heart disorder.