Pyroptosis in cardiovascular diseases: molecular mechanisms, pathological roles, and therapeutic implications

Oct 22, 2026

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Each year, cardiovascular diseases (CVDs) claim millions of lives worldwide, with inflammation serving as a key driver of onset and progression. This review clarifies the mechanistic role of pyroptosis in CVDs and summarizes current progress on pyroptosis-pathway targeted therapies. Pyroptosis is an inflammatory programmed cell death mediated by inflammasomes and gasdermin complexes. Evidence links pyroptosis to atherosclerosis, ischemia-reperfusion injury, myocardial infarction, and heart failure, and highlights NLRP3, caspase-1, and GSDMD as intervention targets.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages32

Reading Time1 h 21 min

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Introduction

Pyroptosis in cardiovascular diseases: mechanisms and therapeutics

Inflammatory caspases and gasdermin-mediated pore formation

Pyroptosis roles in atherosclerosis, myocardial infarction, and heart failure

Therapeutic implications and targets

Am J Cardiovasc Dis 2025;15(6):477-508 [www.AJCD.us](www.AJCD.us /ISSN:2160-200X/AJCD0168800)[ /ISSN:2160-200X/AJCD0168800](www.AJCD.us /ISSN:2160-200X/AJCD0168800) Review Article Pyroptosis in cardiovascular diseases: molecular mechanisms, pathological roles, and therapeutic implications Xue-Song Liu1*, Zhao-Yu Li2*, Shi-Tong Wang3,4*, Qian Qiao5,6,7, Xue-Rui Ye5,6,7, Lu Cheng5,6,7, Yong Hu5,6,7, Lei Zhu5,6,7, Jian-Lin Yang5,6,7, Hao-Ling Zhang8, Jing-Jing Zhang5,6,7 1Basic Medical College, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China; 2College of Acupuncture-Moxibustion and Tuina, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China; 3Henan University of Chinese Medicine, Zhengzhou 450000, Henan, China; 4Department of Cardiac Center, First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan, China; 5Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming 650000, Yunnan, China; 6Yunnan Provincial Cardiovascular Clinical Medical Center, Kunming 650000, Yunnan, China; 7Yunnan Provincial Cardiovascular Clinical Medical Research Center, No. 528, Shahe North Road, Kunming 650000, Yunnan, China; 8Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia. *Co-first authors. Received September 15, 2025; Accepted December 8, 2025; Epub December 15, 2025; Published December 30, 2025 Abstract: 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 CVDsand to summarize the current progress of potential therapeutic strategies targeting pyroptotic pathways. Pyroptosisis 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, includingthe 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. Keywords: Pyroptosis, inflammation, atherosclerosis, myocardial infarction, heart failure, cardiovascular diseases Introduction CVDs are still one of the main causes of illness and death around the world. Threatens human health severely major subtypes like coronary artery disease (CAD), MI, HF, arrhythmias, along with risk factors such as hypertension, diabetes, obesity, and smoking. At the mechanistic level, inflammation is recognized as a crucial instigator in CVD initiation and progression. It occurs through the whole process from plaque formation and rupture to myocardial injury and ventricular remodeling. Elevated levels of inflammatory cytokin

FAQs

What is pyroptosis and how does it relate to cardiovascular diseases?

Pyroptosis is an inflammatory form of programmed cell death mediated by inflammasomes and gasdermin complexes. It contributes to multiple CVD processes by amplifying inflammatory signaling and tissue injury.

Which cardiovascular conditions are discussed as being influenced by pyroptosis?

The review discusses pyroptosis involvement in atherosclerosis, ischemia-reperfusion injury, myocardial infarction, and heart failure, linking it to endothelial disruption, plaque instability, and adverse remodeling.

Which molecular targets are highlighted for potential pyroptosis-based therapies?

Therapeutic interventions focusing on NLRP3 inflammasome, caspase-1, and gasdermin D (GSDMD), as well as combination approaches such as antioxidants and inflammation inhibitors, are reported to show cardioprotective effects.

Oct 22, 2026

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