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Review
. 2022 May 11:9:897815.
doi: 10.3389/fcvm.2022.897815. eCollection 2022.

Pyroptosis: Role and Mechanisms in Cardiovascular Disease

Xinzhe Chen  1 , Peng-Chao Tian  2 , Kai Wang  1 , Man Wang  1 , Kun Wang  1
Affiliations
Review

Pyroptosis: Role and Mechanisms in Cardiovascular Disease

Xinzhe Chen et al. Front Cardiovasc Med. .

Abstract

Cardiovascular disease (CVD) is a common disease that poses a huge threat to human health. Irreversible cardiac damage due to cardiomyocyte death and lack of regenerative capacity under stressful conditions, ultimately leading to impaired cardiac function, is the leading cause of death worldwide. The regulation of cardiomyocyte death plays a crucial role in CVD. Previous studies have shown that the modes of cardiomyocyte death include apoptosis and necrosis. However, another new form of death, pyroptosis, plays an important role in CVD pathogenesis. Pyroptosis induces the amplification of inflammatory response, increases myocardial infarct size, and accelerates the occurrence of cardiovascular disease, and the control of cardiomyocyte pyroptosis holds great promise for the treatment of cardiovascular disease. In this paper, we summarized the characteristics, occurrence and regulation mechanism of pyroptosis are reviewed, and also discussed its role and mechanisms in CVD, such as atherosclerosis (AS), myocardial infarction (MI), arrhythmia and cardiac hypertrophy.

Keywords: cardiovascular disease; caspase; gasdermin; inflammasome; pyroptosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Role of GSDMD in canonical inflammasome activation. The canonical pathway of pyroptosis. PAMPs or DAMPs bind to inflammasome to activate caspase-1, cleaving GSDMD to form GSDMD-C and GSDMD-N. GSDMD-N cluster and bind to the plasma membrane to form GSDMD pores. Simultaneously activated caspase-1 activates IL-18 and IL-1β, and cytokines IL-18 and IL-1β are released into the cell through the GSDMD pore. In addition to IL-18 and IL-1β, HMGB1 is also removed.
FIGURE 2
FIGURE 2
Role of GSDMD in non-canonical inflammasome activation. The canonical pathway of pyroptosis. When LPS enters cells, it directly participates in and activates human caspase-4 and caspase-5 and mouse caspase-11. Caspase-11 cleaves GSDMD, forming GSDMD-C and GSDMD-N. GSDMD-N cluster and bind to the plasma membrane. Formation of GSDMD pore, the formation of GSDMD pore activates inflammasome to bind to caspase-1, activated caspase-1 activates IL-18 and IL-1β, and cytokines IL-18 and IL-1β are released extracellularly through GSDMD pore.
See this image and copyright information in PMC

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