Atherosclerosis (AS), a significant contributor to cardiovascular disease (CVD), is steadily rising with the aging of the global population. Pyroptosis and apoptosis, both caspase-mediated cell death mechanisms, play an essential role in the occurrence and progression of AS. The human pineal gland is the primary producer of melatonin (MT), an indoleamine hormone with powerful anti-oxidative, anti-pyroptosis, and anti-apoptotic properties. This study examined MT's antioxidative stress and anti-pyroptotic effects on human THP-1 macrophages treated with nicotine. Our research found that MT downregulated NOD-like receptor family protein 3 (NLRP3) inflammasome, ASC, and caspase-1 expressions and abrogated the release of Interleukin-1β (IL1β) and Interleukin-18 (IL-18), indicating effective pyroptosis inhibition. These changes were paralleled by a reduction in reactive oxygen species (ROS) production, reversal of sirtuin3 (SIRT3), and Forkhead box O3 (FOXO3α) upregulation. The findings suggest that MT is a viable strategy for counteracting pyroptosis and apoptosis in AS patients by up-regulating SIRT3, promoting FOXO3α, and suppressing ROS production. In inhibiting pyroptosis, MT also inhibits apoptosis, mainly caused by the interaction of caspase-1 and caspase-3 proteins. In vivo studies using ApoE-/- mice confirmed that nicotine could accelerate plaque formation caused by high-fat diets. Moreover, mice treated with MT showed a significant reduction in AS lesion area and increased in cellulose level. Importantly, our understanding of the inhibitory pathways for macrophage pyroptosis will allow us to identify other novel therapeutic targets that will help treat, prevent, and reduce AS-associated mortality.

Background Perioperative coronary artery spasm (CAS) following coronary artery bypass grafting (CABG) is a severe or lethal condition that is rarely reported. In addition, rare cases with CAS following CABG in the non-manipulated coronary artery are angiographically documented in the perioperative period. We aimed to report our experiences on the diagnosis and treatment of a case with CAS following off-pump CABG in the non-manipulated coronary artery. Methods A 57-year old male with coronary heart disease and unstable angina willing to undergo CABG was admitted to our department. CABG was recommended as he showed 90% stenosis in distal left anterior descending artery, 90% stenosis in intermediate branch, 90% stenosis in left circumflex coronary artery, as well as 50% stenosis in proximal right coronary artery (RCA). Results After CABG, the patient showed Adams–Stokes syndrome and ST-segment elevation. Then CPR was conducted and coronary angiography indicated perioperative CAS in the non-manipulated posterior descending artery. For the treatment, the patient received nitroglycerin injection into the coronary artery by catheter and pumping of diltiazem. Finally, the patient was discharged on day 7 after surgery. A comprehensive literature search was conducted to summarize the studies focused on the diagnosis and treatment of such condition, which indicated that all of the CAS cases occurred in the manipulated vessels, except one study showing CAS in the untouched native coronary artery which was similar with our case. Conclusions Perioperative CAS in the non-manipulated coronary artery following CABG is a severe or lethal condition that is rarely reported, which deserves close attention by the clinicians in clinical practice.