This study combined human aspirin–niacin dosing with mouse genetic models to investigate PGD2 production and its cardiovascular effects. Niacin increased urinary PGD2 metabolites, and low-dose aspirin suppressed this response even 24 hours after dosing. DP1 deletion accelerated hypertension and aneurysm in male mice and thrombosis and atherosclerosis in females, supporting a protective role for PGD2.
Alternative hypothesis: A substantial portion of niacin-induced PGD2 derives from nonplatelet COX-1–expressing cells. Antibody depletion lowered the platelet count from 8.1 × 10⁸ to 0.1 × 10⁸ per ml, yet the niacin-evoked PGDM increment was reported as only 41% suppressed, against 91% with COX-1 knockdown in a different mouse strain (Supplemental Figure 6). Any response surviving near-total platelet removal may come from other COX-1–expressing cells, and the sustained aspirin suppression in Figure 6A would be consistent with that if COX-1 recovery in nucleated cells is slower than assumed.
Ideally, platelet-specific COX-1 deletion would be tested during niacin administration: near-complete loss of the PGDM response would support a predominantly platelet source, whereas substantial persistence would favor other cells. Or, at minimum, reporting whether PGDM rises above its own pre-niacin baseline in the depleted group would settle how much is platelet-independent, from data already collected.