CASP1 and hyperlipidemia: In addition to PAMPs derived from microbes, ECs express caspase 1/inflammasomes (38), one type of PAMPs/DAMPs receptors (PRRs) (2), and sense metabolites-derived conditional DAMPs, as we reported (39, 40), from CVD risk factors such as hyperlipidemia (8, 41), hyperhomocysteinemia (42), uremia toxins associated with CKD (20), and hypoxia (12), which activate ECs and accelerate vascular inflammation (17, 20) and atherosclerosis (43, 44).