# The Role of Macrophage Dynamics in Atherosclerosis Analyzed Using a Petri Net-Based Model
## 3 Results and Discussion
### Presentation of the Model and the Results of Its Formal Analysis
\begin{table}
\begin{tabular}{l l l l l l} \hline \hline
**Transition** & **Biological Meaning** & **References** & **Transition** & **Biological Meaning** & **References** \\ \hline \multirow{3}{*}{\(t_{5}\)} & PSGL-1 of monocyte and & & & & \\  & endothelialselectin & [54] & \(t_{26}\) & IL-10 production & [8; 56] \\  & interaction & & & & \\ \hline \multirow{3}{*}{\(t_{6}\)} & chemokine secretion & [34; 55] & \(t_{27}\) & monocyte differentiation & \\  & & from Lyc6C\({}^{Lou}\) & [8; 34; 50; 56] \\ \hline \multirow{3}{*}{\(t_{7}\)} & enhanced monocyte & & & & \\  & production in bone marrow & [8; 34; 54; 57] & \(t_{28}\) & inflammatory milieu chronically & \\  & & & & activating macrophages & \\ \hline \multirow{3}{*}{\(t_{8}\)} & CMP and GMP expansion in & & & & \\  & bone marrow & & & & \\  & & & & & \\ \hline \multirow{3}{*}{\(t_{9}\)} & cleavage of CXCR on & & & & \\  & HSPCs via increasing & & & & \\  & proteolytic activity caused & [57] & \(t_{30}\) & decreased expression of LXR & [38] \\  & by neutrophils & & & & \\ \hline \multirow{3}{*}{\(t_{10}\)} & HSPC shift from the bone & & & & \\  & marrow into spleen, & [38; 57] & \(t_{31}\) & eNOS expression & [58] \\  & lungs, liver & & & & \\ \hline \multirow{3}{*}{\(t_{11}\)} & extramedullary & & & & \\  & hematopoiesis & [38; 53] & \(t_{32}\) & pathway in HSPCs due to & [38] \\  & & & & & \\  & & & & \\  & & & & \\ \hline \multirow{3}{*}{\(t_{12}\)} & \multirow{3}{*}{low CXCL12 expression} & [38; 57] & \multirow{3}{*}{\(t_{33}\)} & cell surface expression of cytokine & \\  & & & & receptors such as IL-3R\(\beta\) & [38] \\  & & & & and M-CSFR & \\ \hline \multirow{3}{*}{\(t_{13}\)} & HSPC mobilization, & & & & \\  & dramatic expansion, and & [38; 57] & \(t_{34}\) & high NR4A1 expression in & \\  & proliferation & & & & Ly6C\({}^{Ligh}\) monocytes & [9] \\ \hline \multirow{3}{*}{\(t_{14}\)} & decreasing the number of & & & & \\  & bone marrow macrophages & [38; 57; 58] & \(t_{35}\) & atherosclerotic plaque impacted & [56] \\  & by IL-10 & & & \\ \hline \multirow{3}{*}{\(t_{15}\)} & favoring neutrophils over & & & & \\  & monocytes and macrophages & [58] & \(t_{36}\) & promoting thinning of the & [3; 34] \\ \hline \multirow{3}{*}{\(t_{16}\)} & G-CSF travel to the & & & & \\  & bone marrow & [38; 58] & \(t_{37}\) & enhancement expression of TLR4 & [38] \\ \hline \multirow{3}{*}{\(t_{17}\)} & G-CSF released by & & & \\  & peripheral cells influenced & [38; 58] & \(t_{38}\) & atherosclerotic plaque rupture & [3; 34] \\  & by IL-17 & & & \\ \hline \multirow{3}{*}{\(t_{18}\)} & Th17 activation & [38; 53] & \(t_{39}\) & sudden artery lumen occlusion & [3; 34] \\  & & & & by thrombus & \\ \hline \multirow{3}{*}{\(t_{19}\)} & IL-23 secretion & [38; 53] & \(t_{40}\) & increased local inflammation & [9; 55] \\  & defective cholesterol & & & \\  & homeostasis & [38; 53; 55] & \(t_{41}\) & atherosclerotic plaque formation & [3; 34] \\ \hline \hline \end{tabular}
\end{table} 
Table 2: _Cont._ \begin{table}
\begin{tabular}{l l l l} \hline \hline
**MCT Set** & **Contained Transitions** & **Biological Interpretation** \\ \hline \multirow{3}{*}{\(m_{1}\)} & \(t_{0}\), \(t_{1}\), \(t_{2}\), \(t_{3}\), \(t_{4}\), \(t_{5}\), \(t_{6}\), \(t_{7}\), \(t_{10}\), & Disturbances in cholesterol homeostasis lead to inflammation and oxidative stress, & \\  & \(t_{11}\), \(t_{19}\), \(t_{20}\), \(t_{21}\), \(t_{22}\), \(t_{23}\), \(t_{26}\), & which in turn contribute to monocyte differentiation and the development of & \\  & \(t_{27}\), \(t_{28}\), \(t_{29}\), \(t_{35}\), \(t_{38}\), \(t_{39}\), \(t_{40}\) & atherosclerotic plaque. & \\ \hline \multirow{3}{*}{\(m_{2}\)} & \(t_{30}\), \(t_{32}\), \(t_{33}\), \(t_{37}\) & Decreased expression of key cholesterol transporters in HSPCs due to & \\  & & & \\  & & & \\  & & & \\  & & & \\  & & & \\  & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 3: The MCT sets of the model and their biological interpretations.