As mentioned earlier, upon recognition of stimulatory signals from pathogens such as bacteria and viruses, the intracellular pattern expression receptors activate the inflammatory vesicle junction protein caspase recruitment domain (ASC) to bind with pro-caspase-1 protein forming a protein complex (43) and facilitates the activation of caspase-1 (44, 45). The activated caspase-1, cleaves GSDMD to form a peptide containing the nitrogen-terminal active domain of GSDMD and induces cell membrane perforation and cell rupture, releasing the contents and causes an inflammatory response.The activated caspase-1 can also cleave the precursors of IL-1β and IL-18 to form active IL-1β and IL-18, which are released into the extracellular space and recruit inflammatory cells to aggregate and amplify the inflammatory response (46, 47).

In contrast to the classical pathway, human caspase-4/5 and mouse caspase-11 can bind to bacterial lipopolysaccharides (LPS), mediating inflammation and leading to cellular necrosis (48, 49). Caspase-4/5 and 11 can also be activated in response to stimulation by signals such as bacteria. Activated caspase-4/5 and 11 cleave GSDMD and form peptides containing the nitrogen-terminal active domain of GSDMD (50, 51). GSDMD induce cell membrane perforation, cell rupture and release of contents, causing an inflammatory response. GSDMD induces activation of caspase-1and cleaves the precursors of IL-1β and IL-18, forming active IL-1β and IL-18, and releasing them extracellularly to recruit inflammatory cells to aggregate and amplify the inflammatory response. In addition, activated caspase-11 can induce cellular inflammatory reactions by inducing membrane pore formation in GSDMD cells and promoting K + efflux through the Pannexin-1/ATP/P2X7 pathway, mediating NLRP3/ASC/caspase-1 activation and promoting IL-1β maturation and release. Both of these activation pathways can cleave GSDMD to induce the formation of cell membrane gaps and also stimulate the activation of IL-1β and IL-18 to promote a more intense extracellular inflammatory response.

Another caspase-3-dependent pyroptosis pathway differing from caspase-1/4/5/11 has recently been identified, which induces GSDMD-dependent pyroptosis, in that caspase-3 induces cell pore formation by cleaving GSDME and promoting the recruitment of the GSDME-N structural domain to the cell membrane, leading to pyroptosis (39). The distribution and expression level of GSDME determines how caspase-3 activates cell death. When cells overexpress GSDME, activated caspase-3 induces cell pyroptosis, whereas, for cells with low GSDME expression, caspase-3 induces apoptosis after activation of caspase-3 induces apoptosis. This caspase-3-dependent mode of cell death is known as apoptosis-like pyroptosis (52).

To some extent, pyroptosis is a double-edged sword. On the one hand, moderate pyroptosis contributes to cellular homeostasis and can effectively prevent excessive cell proliferation, thereby protecting the host (53).On the other hand, high levels of pyroptosis can lead to inflammation, which is detrimental to the maintenance of homeostasis in vivo. There is growing evidence that pyroptosis may be an effective anti-microbial defence mechanism in the host during infection. Pyroptosis eliminates pathogenic bacteria by lysing infected cells and exposing pathogens to extracellular defences, such as by telling pathogens to neutrophils with solid anti-microbial activity. In addition, pyroptosis facilitates pathogen clearance by sensing an alarm signal from immune cells recruited to the site of infection. During pyroptosis, IL-1β (54) and IL-18 are released extracellularly as cell integrity is disrupted, promoting leukocyte infiltration and activation. The release of inflammatory mediators by cell lysis, including factors such as ATP (55), IL-1 and heat shock proteins, stimulates the production of pro-inflammatory cytokines by activating pattern recognition receptors, which contribute to the control and eventual resolution of microbial infections and their return to a homeostatic state (2, 56).

However, mutations in intracytoplasmic receptors [NOD-like receptors (NLR)] or the persistence of sterile inflammatory stimuli can lead to excessive pyroptosis (2), which can be detrimental to the host and, if left unchecked, can lead to disease (57, 58). Excessively pyroptosis cells increase the inflammatory mediators IL-1β, IL-18 and the alarm protein HMGB-1. HMGB-1 has been reported to cause severe sepsis and infectious shock (59). This can harm the host and, if left unchecked, can lead to disease.

Diabetic cardiomyopathy (DCM) is a disease featured witn substantial cardiac lesion characterised by myocardial fibrosis and cardiac hypertrophy caused by chronic diabetes mellitus that occurs in the absence of hypertensive heart disease, coronary artery disease and heart valve disease (73). Several studies have shown that DCM is partially associated with pyroptosis, the most classic being myocardial fibrosis mediated by caspase-1 activation in a high-glucose environment: the lncRNA Kcnq1ot1, a signalling lncRNA, is highly expressed in the left ventricular tissue of diabetic mice, and a recent study by Fan Yang et al. showed that knockdown of Kcnq1ot1 by small interfering RNA reduced the expression of caspase-1 (10). The levels of NLRP3, caspase-1, IL-1β and GSDMD-N were significantly increased in the cardiac tissues of diabetic mice. However, their levels were significantly reduced by immunohistochemical analysis after kcnq1ot1 silencing (74). NLRP3, caspase-1 and IL-1β mRNA and protein expression levels were significantly elevated in diabetic (DM) mice and were reversed after kcnq1ot1-shRNA treatment. In addition, GSDMD-N protein expression levels were significantly elevated in diabetic mice and reversed after kcnq10t1 inhibition, and these effects were achieved through a complementary regulatory relationship between kcnq10t1 and miR-214-3p, caspase-1 and miR-214-3p (10). At the tissue level, kcnq1ot1 regulates caspase-1 expression in cardiac fibroblasts via miR-214-3p and thereby reduces irreversible myocardial fibrosis due to myocyte pyroptosis, as evidenced by the elevation induced by kcnq1ot1 silencing, leading to significant inhibition of miR-214-3p-targeted caspase-1 and its downstream inflammatory cytokine IL-1β is significantly inhibited (75). Previous studies have shown that IL-1β is closely associated with cardiac fibrosis and that prolonged exposure to IL-1β activates the TGF-β1 pathway, inducing the conversion of microvascular endothelial cells to myofibroblasts (76), leading to increased collagen synthesis, promotion of myocardial remodelling and increased interstitial myocardial fibrosis. lncRNA kcnq10t1 regulates pyroptosis in the diabetic heart possibly through kcnqot1/miR-214-3p/caspase-1/TGF-β1 pathway.

LncRNA Growth inhibitor-specific transcript (GAS5) has been reported to regulate various cardiac functions through pyroptosis (77), such as inhibition of cardiac hypertrophy, reduction of cardiac fibrosis and improvement of myocardial ischemia and hypoxia leading to cardiac dysfunction. Recent microarray analysis of lncRNA profiles in an in vitro DCM model (78) showed significant downregulation of GAS5 in cardiomyocytes. A study showed that GAS5 improved cardiac function and myocardial hypertrophy in DCM mice (15). GAS5, a competitive endogenous lncRNA, enhanced the aryl hydrocarbon receptor (AHR) expression by suppressing miR-34b-3p, thereby inhibiting NLRP3 inflammatory vesicle activation-mediated energy. miR-34b-3p upregulation in the DCM model significantly enhanced caspase-1 activity and levels of IL-1β and IL-18 in HL-1 cells, whereas GAS5 overexpression effectively abolished caspase-1 activity (79). LncRNA GAS5 regulates pyroptosis in the diabetic heart, possibly by targeting GAS5/miR-34b-3p/AHR to inhibit NLRP3 inflammatory vesicle activation in diabetic cardiomyopathy achieve.

In recent years, many lncRNAs have been reported to be involved in regulating diabetic cardiomyopathy by mediating pyroptosis. For example, MALAT1 expression is increased in the diabetic heart (80). Its knockdown improves cardiac contractile function and reduces inflammatory factors such as TNF-α, IL-6 and IL-1β in the diabetic myocardium, thus suggesting that MALAT1 may be involved in the inflammatory response to diabetic cardiomyopathy. Another study reported that MALAT1 upregulates inflammatory mediators TNF-α and IL-6 in high-glucose-treated endothelial cells by activating serum amyloid antigen. Large amounts of circulating lncRNA such as LIPCAR, SENCR and MIAT are valuable predictors of left ventricular diastolic function and remodelling in diabetic patients.

Many studies have revealed that several lncRNA, including MIAT and kcnq1ot1, are associated with DCM through inflammatory mechanisms. LncRNA myocardial infarction-associated transcript (MIAT) alleles, a lncRNA enriched in diabetic cardiomyocytes, act as competing endogenous RNAs (ceRNAs), forming a feedback loop with vascular endothelial growth factor. Furthermore, MIAT, CASP1 and IL-1b expression levels were upregulated and miR-214-3p expression levels were downregulated in serum of diabetic patients (81). In contrast, MIAT-silenced myocardial tissue of DM mice was associated with myocardial infarction compared to the regular group. Protein expression of caspase-1, IL-1b, IL-18, and GSDMD was significantly down-regulated and miR-214-3p expression was upregulated in MIAT-silenced myocardial tissue compared to the regular group, with the same results in both human and mouse genera (81, 82). Similarly, mRNA expression of caspase-1 and IL-1b was significantly reduced and miR-214-3p expression was elevated in mouse hearts following MIAT knockdown or caspase-1 inhibitor application, suggesting that MIAT may affect cellular pyroptosis in diabetic cardiomyopathy by targeting miR-214-3p to regulate the expression of caspase-1 and IL-1b process. It has been shown that MIAT is involved in both left ventricular diastolic function and myocardial remodelling in diabetic patients (83).

Pyroptosis-mediated inflammation in vascular endothelial cells and cardiomyocytes is essential in the late complications of cardiac dysfunction in diabetic patients. LncRNAs can regulate the development of diabetic cardiomyopathy by mediating the activation of pyroptosis-associated factors and affecting ventricular remodelling through multiple pathways that interfere with the integrity of cardiomyocytes and vascular endothelial cells, giving us many hints and motivation for research. The causal relationship and consequences of pyroptosis and chronic inflamation in cadiac myppathy are still to be further studied.

CVD caused by atherosclerosis (AS) is the major cause of mortality in the global population (84). Pyroptosis as a form of inflammation-mediated cell death has become the focus of research to advance the pathological process of atherosclerosis (60, 85). Endothelial cell dysfunction is the earliest link in the development of atherosclerosis. Therefore, maintaining endothelial cells' integrity and normal function is essential to prevent and treat atherosclerosis (86).

Research on the role of lncRNAs in the pathology of atherosclerosis is still in its infancy. Several lncRNAs have been identified as being involved in the development of atherosclerosis (87). Atorvastatin is commonly used to control abnormal lipid metabolism in patients with atherosclerosis. Wu et al. demonstrated that atorvastatin can be expressed at both mRNA and protein levels by upregulating the expression of Nexilin F-actin binding protein antisense RNA1 (lncRNA NEXN-as1) and NEXN Reduction of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 to inhibit pyroptosis (87). In RT-PCR analysis of samples from the clinic, RNA levels of NEXN and NEXN- as1 were lower in patients' atherosclerotic plaques than in healthy intimal tissue; their expression levels would be lower in advanced atherosclerotic plaque tissue. Recent study demonstrated that overexpression of NEXN-as1 inhibited NF-κB activity and downregulated endothelial cell adhesion molecules and inflammatory factors (87). These inhibitory effects of NEXN-as1 were abolished by knocking down NEXN: artificial knockdown of NEXN in Apoe knockout mice promoted atherogenesis, increased macrophage abundance in atherosclerotic lesions, and increased expression of adhesion molecules and inflammatory cytokines, whereas increased NEXN expression prevented atherosclerosis (88). In contrast, NEXN-as1 can protect against the progression of atherosclerosis by interacting with the chromatin remodeler BAZ1A and upregulating its homologous protein-encoding gene NEXN, thereby inhibiting endothelial cell activation and monocyte recruitment, ultimately providing protection against atherosclerosis progression (89). In addition, NEXN- as1 and NEXN may promote plaque stabilization by inhibiting adhesion molecules and extracellular matrix-degrading enzymes and reducing macrophage abundance and lipid content, hallmarks of vulnerable atherosclerotic plaques.

The expression of NLRP3 is increased in the aorta of patients with coronary artery disease, and its expression correlates with the severity of coronary artery disease (90). Various lncRNAs are involved in NLRP3 activation during pyroptosis, for example, lncRNA MALAT1 associated with NLRP, with low mustard acid reducing NLRP3 gene expression in macrophages by decreasing lncRNA MALAT1, and lncRNA MALAT1 promoting NLRP3 gene expression in myocardial ischemia-reperfusion injury (91–93).

In addition, recent studies suggest that the lncRNA-miRNA-mRNA regulatory network may play a vital role in the cellular pyroptosis process (8, 94). LncRNA MALAT1 may use this network to regulate NLRP3 expression by adsorbing endothelial cell miR-22 through a competitive inside-supporting RNA mechanism. By observing human umbilical vein endothelial cells transfected with miR-22 in a high glucose culture environment, the expression level of miR-22 decreased significantly after high glucose stimulation, while the level of lncRNA MALAT1 in endothelial cells changed in contrast to miR-22; overexpression of miR-22 could attenuate MALAT1's pyroptosis of endothelial cells induced by high glucose, suggesting that MALAT1/miR-22/NLRP3 regulatory pathway is involved in high-glucose-induced endothelial cell pyroptosis (95).

The involvement of the lncRNA-miRNA-mRNA regulatory network in mediating pyroptosis-induced endothelial cell damage and hence atherosclerosis applies to many existing studies: melatonin reduced ox-LDL-induced pyroptosis in human aortic endothelial cells by decreasing the lncRNA MEG3, and the possible molecular mechanism was that the adsorption of miR-223 by MEG3 unlocked the target gene NLRP3. Han et al. found (63) that low doses of erucic acid reduced the lncRNA MALAT1, thereby reducing macrophage pyroptosis in diabetic atherosclerotic rats, probably through the MALAT1/miR-23c/ELAYL1 pathway. LncRNAs may act as significant regulators of pyroptosis in atherosclerotic heart disease and are potential therapeutic targets, but further studies are needed to demonstrate their utility as biomarkers.

Myocardial infarction (MI) is a severe coronary artery-related disease caused primarily by ruptured atherosclerosis or an imbalance in the supply and demand of oxygen to the heart muscle (96). When atherosclerosis ruptures, the released plaque collects platelets and causes occlusion of the coronary arteries, leading to ischaemic necrosis of the myocardium (97). Like atherosclerosis, pyroptosis is involved in cardiomyocyte injury by mediating the inflammatory response, and the pyroptosis pathway is also a potential therapeutic target for cardiovascular disease (98). It is considerable evidence that lncRNAs act as competing ceRNAs in myocardial infarction to regulate cellular biological activity in a manner that mediates the processes of the pyroptosis network.

Many recent bioinformatic predictions of the involvement of lncRNAs in mediating the pyroptosis pathway in regulating myocardial infarction have been confirmed (98). For example, the lncRNA KLF3-AS1/miR-138-5p/Sirt1 in exosomes from human mesenchymal stem cells (hMSCs) is involved in the protective effect on hypoxic cardiomyocytes (11). The myocardial infarction area was significantly reduced in rats with myocardial infarction injected with KLF3-AS1 exosome, and the expressions of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 in KLF3-AS1-overexpressed myocardial infarction mice were also significantly decreased. The term of KLF3-AS1 and Sirt1 was upregulated after transfection with miR-138-5p inhibitor (99). Transfection with Sirt inhibitor reversed the protective effect of KLF3-AS1 on hypoxic cardiomyocytes, suggesting that lncRNA KLF3-AS1 acts as a competitive endogenous RNA by inhibiting miR-138-5p from regulating the expression of Sirt1 and thus inhibiting the activation of pyroptosis factor of the lncRNA KLF3-AS1, as a ceRNA, inhibits the activation of Sirt1 and thus protects cardiomyocytes (11, 100). Another study found that Sirt1 was downregulated in myocardial infarction and that Sirt1 overexpression effectively ameliorated myocardial injury caused by myocardial infarction. Data from vascular endothelial cells showed that Sirt1 inhibited the expression of NLRP3 and ASC in addition to the maturation of caspase-1 and the inflammatory cytokine IL-1β, suggesting that Sirt1 has an inhibitory effect on the activation of NLRP3 inflammatory vesicles and that Sirt1 has a protective effect on vascular endothelial cells.

Another bioinformatically predicted and validated pathway is the lncRNA FAF/miR-185-5p/PAK2 axis that mediates cardiomyocyte pyroptosis to ameliorate acute myocardial infarction. lncRNA FGF9 associated factor (FAF) is a recently identified pathway downregulated in infarcted myocardium and inhibits cardiomyocyte pyroptosis through transcriptional regulation of FGF9. Li et al. also demonstrated that the downregulation of miR-185-5p expression contributed to endothelial neovascularisation, which further reduced the decline in cardiac function in mice after infarction (101). Overexpression of the lncRNA FAF in the myocardium improved the pathological ultrastructural changes associated with acute myocardial infarction, such as myofilament lysis, loss of plasma membrane integrity, mitochondrial swelling and loss of cristae (102). Pathological changes. In addition, overexpression of myocardial lncRNA FAF in the rat myocardial ischemia/hypoxia model protected the membrane integrity of hypoxia/ischemia-induced focal cell death better than the control group. Recent report indicated that rat myocardial cells under hypoxia/ischemia induction showed significant cytosolic rounding, bubbles on the cell surface with bulging masses, and myocardial cells in the hypoxia and FAF overexpression group showed significantly reduced morphological differences (14). It has also been shown that modulation of miR-185-5p and PAK2 can exert cardioprotective effects. Furthermore, PAK2 expression was downregulated in hypoxic and ischemic cardiomyocytes. That overexpression of lncRNA FAF upregulated PAK2 protein levels under hypoxic conditions, reversed under transfected miR-185-5p co-culture conditions. Transfection with miR-185-5p inhibitor helped to reduce cellular pyroptosis, and in contrast, miR-185-5p mimicked the increased cellular pyroptosis under hypoxic ischemia. It is reasonable to believe that lncRNA FAF promotes the release of PAK2 by inhibiting the miR-185-5p pyroptosis pathway, which attenuates the cellular pyroptosis response and reduces the size of myocardial infarction.

In addition, pyroptosis-induced inferior coronary micro thrombosis is an essential pathogenesis of myocardial infarction. Coronary microemboli induce inflammatory responses and oxidative stress in the body in additiong to its blockage of blood stream. Microemboli leading to a collective burst of inflammatory reactions have recently been found to be mediated by various lncRNAs. LncRNA Sox2 overlapping transcripts (Sox2OT), a long-stranded non-coding RNA localized to the human chromosome 3q26.3 (Chr3q26.3) locus, a long-stranded non-coding RNA with an intron region containing the Sox2 gene, which is one of the primary regulators of pluripotency (13). Sox2OT was previously reported to enhance cardiac dysfunction by promoting re-releasing of reactive oxygen species (ROS) in mice with septic cardiomyopathy (103). Recently, the ability of Sox2OT to act as a competitive ceRNA in inducing various pyroptosis pathways has been increasingly demonstrated. In a recent survey, Xuan et al. concluded that silencing Sox2 downregulates NF-κB expression in cardiomyocytes, an effect that may be mediated by the miR-23b/TLR4/LPS pyroptosis pathway (13). Pyroptosis is a caspase-1-dependent form of programmed cell death inflammation. NF-κB upregulates pyroptosis-associated inflammasome NLRP3 levels, activates caspase-1 activity and promotes GSDMD expression, promoting the inflammatory response and inducing pyroptosis. In the rat infarct model, silencing of Sox2OT decreased NF-κb p65 phosphorylation and downregulated NLRP3, GSDMD and caspase-1 protein levels compared to the average infarct model, whereas overexpression of Sox2OT had the opposite result. RISC is a ribonucleoprotein complex containing proteins such as Argonaute (Ago) that binds mature miRNAs, mediates post-transcriptional gene silencing or mRNA target gene degradation, and is involved in the regulation of gene expression. The detection of lncRNA Sox2OT and miR-23b at the exact location and highly enriched using Ago magnetic antibody beads indicates that Sox2OT and miR-23b are in the same Ago complex. It was speculated that Sox2OT and miR-23b were in the same Ago difficult, the miR-23b level was increased, and the expression of TLR4 and NF-κb was significantly down-regulated in the silenced Sox2OT group. These results indicate that Sox2OT regulates TLR4 and mediates TLR4/NF-κb signalling pathway as a ceRNA of miR-23b. The effect of Sox2OT on miR-23b/TLR4/NF-κb may guide a novel therapeutic course for coronary embolism-induced acute heart attack. Therapeutic pathway for acute heart attacks caused by coronary embolism. More on the effect of lncRNAs on infarction lies in imaging ventricular remodelling, e.g., myocardial infarction-associated transcript 1 (Mirt1) expression correlates with the characterization of genes related to left ventricular remodelling (104); GAS5 overexpression improves new function and ventricular hypertrophy in a mouse model of myocardial infarction, all of which are of great research value.

In the study of lncRNAs mediating the development of acute myocardial infarction, many lncRNAs were found to be differentially regulated. Whether the regulatory effects of these lncRNAs, taken together, contribute to attenuating myocardial cell injury and ventricular remodelling by pyroptosis requires further validation.