Table 2.

List of t-clusters. The column “t-cluster” contains the names of t-clusters. The column “Biological meaning” includes biological interpretations of t-clusters.

t-Cluster	Biological Meaning
$c_1$	TRAIL-induced apoptosis signaling pathways. Increased quantity of cFLIP leads to inhibition of caspase 8.
$c_2$	The mitochondria-involved intrinsic apoptotic pathway. The intrinsic pathway arises from signals that originate within the cell, as a consequence of cellular stress or DNA damage. High level of IL-10 has an influence on development of anti-inflammatory processes. Damage to mitochondria and subsequent apoptosome-mediated caspase 9 activation, which directly activate the effector caspase, caspase 3.
$c_3$	The mitochondria-involved intrinsic apoptotic pathway, similar to $c_3$, accompanied by cleavage and activation of caspases 3, 6 and 7.
$c_4$	TWEAK leads to the reaction catalyzed by NADPH oxidase, which results in peroxynitrite production. Macrophages M2 cause TWEAK sequestration in case of high level of IL-10. Peroxynitrite is engaged in lipids peroxidation and results in the production of modified oxidized LDL. This modified oxidized LDL together with IL-18 lead to neighboring endothelial cell stimulation and secretion of MCP1 (IL-18 is produced in caspase 1-independent pathway).
$c_5$	This cluster contains almost all processes included in the model, however it is missing: Caspase 1 inhibition caused by NO. TNFR1 endocytosis from TRAF2-TRADD-RIP1-TRAF5 complex, which leads to omission of FADD. Damage to mitochondria and subsequent apoptosome-mediated caspase 9 activation.
$c_6$	Attracting of monocytes caused by MCP1, VCAM1, ICAM1 (secreted via p50/p65 translocation to the nucleus in macrophages M1 and SMC and EC) and TRAIL (in oncogenesis) lead to a lot of classically activated macrophages M1. In oncogenesis TRAIL and death receptors trimerization leads to pro-caspase 8 recruitment by FADD. Connection through DDs within FADD and TNFR result in active DISC type I cells and increased quantity of cFLIP. cFLIP together with TRAF2-TRADD-RIP1-TRAF5-TNFR1 complex lead to TRAF2 ubiquitination and in consequence to RIP1 ubiquitination. RIP1 recruits TAK1 via TAB2, which is part of IKK complex engaged in phosphorylation of I$\kappa$B (which stimulate p50/p65 translocation to the nucleus in macrophages M1, SMC and EC). p50/p65 translocation to the nucleus in macrophages M1 and SMC and EC leads to secretion of iNOS, which is associated with NO synthesis. NO synthesis leads also to peroxynitrite production, which together with high level of caspase 8 result in activation of caspases 3, 6 and 7. The high level of caspase 8 is caused by TRAIL and TRAIL death receptors trimerization (in oncogenesis). Active caspases 3, 6, 7 and also TWEAK lead to apoptosis enhancement anti-inflammation. TWEAK sequestration is caused by macrophages M2 in case of high level of IL-10. Moreover, NO is engaged in cardiac contractile dysfunction, which leads to CVD symptoms and cardiovascular events. These symptoms are additionally stimulated by ROS generation and foamy cells, which are associated with NO synthesis.
$c_7$	This cluster contains almost all processes included in the model; however, it is missing: Caspase 1 inhibition caused by NO.
$c_8$	This cluster contains almost all processes included in the model, however it is missing: IL-18 synthesis caused by caspase 1-dependent pathway. However, in this cluster IL-18 is produced in caspase 1-independent pathway. IL-12, IL-1, IL-23 release by classically activated macrophages M1. IFN gamma synthesis, what results in omission of JAK1, JAK2 and STAT1, STAT2 activation and also STAT1 protein via IFN gamma and IFNR. Omission of JAK- STAT1 pathway activation results in a lack of caspase 1 (a lack of modulation by TNF is also present). TNFR1 trimerization, which can create complex with TRAF2-TRADD-RIP1-TRAF5, which leads to the omission of FAD recruitment and TRAF2 ubiquitination.
$c_9$	This cluster contains almost all processes included in the model, however it is missing: IL-18 synthesis caused by caspase 1-dependent pathway. However, in this cluster IL-18 is produced in caspase 1-independent pathway. IL-12, IL-1, IL-23, IL-6 release by classically activated macrophages M1. High level of IL-10 release by alternatively activated macrophages M2. IFN gamma synthesis, which results in omission of JAK1, JAK2 and STAT1, STAT2 activation and also STAT1 protein via IFN gamma and IFNR. Omission of JAK- STAT1 pathway activation results in a lack of caspase 1 (a lack of modulation by TNF is also present). Caspase 8 inhibition.
$c_{10}$	Attracting of monocytes stimulated by TRAIL, MCP1 (by neighboring endothelial cells stimulation) and MCP1, VCAM1, ICAM1 (by p50/p65 translocation to the nucleus in macrophages M1 and SMC and EC) leads to high level of classically activated macrophages M1, which release IL-6, IL-12, IL-1, IL-23. Macrophages M1 are also engaged in the transformation of oxLDL into foamy cells via NO synthesis and lipid peroxidation, which results in progression of atherosclerotic plaque. IL-18 is produced in caspase 1-independent pathway and it can create complex with IL-18R (IL-18R is stimulated by bacterial infections). Active IL-18-IL-18R$\alpha$-IL18R$\beta$ complex recruits MyD88 which is engaged in a pathway of I$\kappa$B phosphorylation. I$\kappa$B phosphorylation stimulates attract of monocytes via p50/p65 translocation to the nucleus in macrophages M1 and SMC and EC, which stimulate MCP1, VCAM1, ICAM1, TNF alpha, iNOS. IL-1 and IL-23 induce Th17 differentiation. Th17 cells are engaged in essential hypertension. IL-6 and high level of IL-10 lead to activation of STAT3 protein, which is engaged in an induction of IL-4 receptor alpha and binding with IL-4. IL-4 and IL-4R complex stimulates anti-inflammatory pathway, which in consequence leads to high level of IL-10. This cluster includes also negative regulation of IL-18. To be precise, IFN gamma leads to interaction with IFNRs, which results in JAK1, 2 and STAT1, STAT2 activation. This activation leads to binding with SBE sequences of IRF1, which result in NO synthesis induced by iNOS. It is important that NO is engaged in caspase 1 inhibition and in consequence leads to negative regulation of IL-18.
$c_{11}$	Attracting of monocytes stimulated by TRAIL, MCP1, VCAM1, ICAM1 (by p50/p65 translocation to the nucleus in macrophages M1 and SMC and EC) lead to high level of classically activated macrophages M1, which release IL-6, IL-12, IL-1, IL-23. IL18 is produced in caspase 1-independent pathway and it can create complex with IL-18R (IL-18R is stimulated by bacterial infections). Active IL-18-IL-18R$\alpha$-IL-18R$\beta$ complex recruits MyD88 which is engaged in a pathway of I$\kappa$B phosphorylation. Moreover, receptor MyD88 complex can be additionally stimulated by LPS-LBP complex (TLR4 and MyD88 connection via TIRAP). I$\kappa$B phosphorylation stimulates attracting of monocytes via p50/p65 translocation to the nucleus in macrophages M1 and SMC and EC, which stimulate MCP1, VCAM1, ICAM1, TNF alpha, iNOS. IL-1 and IL-23 lead to the formation of Th17. Th17 cells are engaged in essential hypertension. IL-6 and high level of IL-10 lead to activation of STAT3 protein, which is engaged in an induction of IL-4 receptor alpha and binding with IL-4. IL-4 and IL-4R complex stimulates anti-inflammatory pathway, which in consequence leads to high level of IL-10. This cluster includes also negative regulation of IL-18. To be precise, IFN gamma leads to interaction with IFNRs, which results in JAK1, 2 and STAT1, STAT2 activation. This activation leads to binding with SBE sequences of IRF1, which result in NO synthesis induced by iNOS. Important is fact, that NO is engaged in caspase 1 inhibition and in consequence leads to negative regulation of IL-18. Binding of TRAIL to death receptors (DR5 and DR4) leads to the recruitment of an adaptor protein FADD, which leads to pro caspase 8 recruitment. The connection through DDs within FADD and TNFR leads to an activation of DISC type I cells. High level of caspase 8 together with peroxynitrite production result in activation of caspases 3, 6 and 7. Active caspases 3, 6, 7 and also TWEAK lead to apoptosis enhancement anti-inflammation.
$c_{12}$	Attract of monocytes stimulated by TRAIL, MCP1 (by neighboring endothelial cells stimulation) and MCP1, VCAM1, ICAM1 (by p50/p65 translocation to the nucleus in macrophages M1 and SMC and EC) leads to high level of classically activated macrophages M1, which release IL-6, IL-12, IL-1, IL-23. Macrophages M1 are also engaged in the transformation of oxLDL into foamy cells via NO synthesis and lipid peroxidation, which results in progression of atherosclerotic plaque. IL-18 is produced in caspase 1-independent pathway and it can create complex with IL-18R (IL-18R is stimulated by bacterial infections). Active IL-18-IL-18R$\alpha$-IL-18R$\beta$ complex recruits MyD88 which is engaged in a pathway of I$\kappa$B phosphorylation. I$\kappa$B phosphorylation stimulates attract of monocytes via p50/p65 translocation to the nucleus in macrophages M1 and SMC and EC, which stimulates MCP1, VCAM1, ICAM1, TNF alpha and iNOS. IL-1 and IL-23 lead to the formation of Th17. Th17 cells are engaged in essential hypertension. IL-6 and high level of IL-10 lead to an activation of STAT3 protein, which is engaged in an induction of IL-4 receptor alpha and binding with IL-4. IL-4 and IL-4R complex stimulates anti-inflammatory pathway, which in consequence, leads to high level of IL-10. Binding of TRAIL to death receptors (DR5 and DR4) leads to the recruitment of an adaptor protein FADD, which leads to pro caspase 8 recruitment. The connection through DDs within FADD and TNFR leads to an activation of DISC type I cells. Increased quantity of cFLIP leads to inhibition of caspase 8.
$c_{13}$	IFN gamma leads to interaction with IFNRs, which results in JAK1, JAK2 and STAT1, STAT2 activation. Activation of pathway of JAK-STAT1 leads to binding with SBE sequences of IRF-1. This process leads to NO synthesis induced by iNOS. NO is engaged in caspase 1 inhibition and in consequence leads to negative regulation of IL-18. NO synthesis leads also to peroxynitrite production, which together with high level of caspase 8 results in an activation of caspases 3, 6 and 7. High level of caspase 8 is caused by TRAIL and TRAIL death receptors trimerization (in oncogenesis). Active caspases 3, 6, 7 and also TWEAK lead to apoptosis enhancement anti-inflammation. TWEAK sequestration is caused by macrophages M2 in case of high level of IL-10.
$c_{14}$	IFN gamma leads to interaction with IFNRs, which results in JAK1, 2 and STAT1, STAT2 activation. Activation of pathway of JAK-STAT1 leads to binding with SBE sequences of IRF1. This process leads to NO synthesis induced by iNOS. NO is engaged in caspase 1 inhibition and in consequence leads to negative regulation of IL-18. NO synthesis leads also to peroxynitrite production, which is engaged in lipid peroxidation and results in production of modified oxLDL. This modified oxLDL together with IL-18 lead to neighboring endothelial cell stimulation and secretion of MCP1 (IL-18 is produced in caspase 1-independent pathway).
$c_{15}$	This cluster contains almost all processes included in the model, however it is missing: IL-18 synthesis caused by caspase 1-dependent pathway. However, in this cluster IL-18 is produced in caspase 1-independent pathway. Increased quantity of cFLIP, which results in omission of caspase 8 inhibition (and apoptosis inhibition) and omission of ubiquitination of TRAF2 and RIR1. Classically activated macrophages M1 via transformation of tissue macrophages. In this case, IL-1, IL-23 and L-12 are not released. IL-1 and IL-23 are engaged in Th17 cell formation, which leads to essential hypertension. IL-12 is engaged in IFN gamma synthesis. In this cluster, IFN gamma synthesis is caused by LPS (bacterial infection).