心血管疾患におけるパイロプトーシス：分子メカニズム、病理学的役割、および治療的含意

Each year, cardiovascular diseases (CVDs) claim millions of lives worldwide, making them one of the biggest causes of deaths globally. More often than not, the inflammatory response is the principal disease mechanism behind the onset and development of CVDs. The study seeks to elucidate the mechanistic role of pyroptosis in CVDs and to summarize the current progress of potential therapeutic strategies targeting pyroptotic pathways. Pyroptosis is a form of PCD, which is inflammatory and mediated through an inflammasome and gasdermin complex. In the past few years, it has emerged as a crucial mechanism possibly explaining protracted inflammation and tissue damage. There is evidence suggesting that pyroptosis contributes to multiple CVDs. Indeed, it may induce disruption of endothelial barrier and plaque instability in atherosclerosis (AS). Also, it may aggravate ischemia-reperfusion injury (IRI) and reduce repair processes in case of myocardial infarction (MI). Finally, it may drive ventricular remodeling and functional impairment in heart failure (HF). Cell death and immune activation are further aggravated by a vicious cycle between pyroptosis and inflammation. Recent studies indicate that therapeutic interventions focused on key molecules, including the NLRP3 inflammasome, caspase-1, and gasdermin D (GSDMD), along with combination therapies consisting of antioxidants and inflammation inhibitors, exhibit significant cardioprotective effects. Additionally, one's diet, exercise and other lifestyle choices impact pyroptotic pathways and influence the risk of CVD. We should include pyroptosis as a form of cell death in future research only. Further, it would be necessary to identify reliable biomarkers for all of these forms of cell death for their therapeutic mechanisms.