Atherosclerosis, the leading cause of cardiovascular disease (CVD), is a chronic inflammatory condition involving immune cells producing pro-inflammatory cytokines. Oxidized low-density lipoprotein (oxLDL) plays a key role, as it is immunogenic, toxic, and contains inflammatory phospholipids with phosphorylcholine (PC) as an epitope. Antibodies against PC may protect against atherosclerosis by reducing inflammation. While bacteria and viruses have been implicated, direct evidence is limited. Heat shock proteins (HSPs) may be targets for immune reactions. Pro-inflammatory cytokines, chemokines, and lipid mediators contribute to plaque rupture. Clinical studies are needed to confirm inflammation's role in atherosclerosis. OxLDL activates endothelial cells, monocytes/macrophages, and T cells, and is toxic at high concentrations. Inflammatory phospholipids like lysophosphatidylcholine (LPC) mimic oxLDL's effects. OxLDL also generates damage-associated molecular patterns (DAMPs), such as malondialdehyde (MDA), which induce inflammation. Dead cells in atherosclerosis can activate the innate immune system, releasing IL-1β and activating the inflammasome. Anti-PC antibodies may reduce atherosclerosis by inhibiting oxLDL uptake and inflammation. HSPs, particularly HSP60, are immunogenic and may contribute to atherosclerosis. Infections like Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus have been linked to atherosclerosis, but evidence is inconclusive. Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is converted to trimethylamine-N-oxide (TMAO), accelerating atherosclerosis. Infections may indirectly promote atherosclerosis by stimulating inflammation. Inflammatory markers like C-reactive protein (CRP) and cytokines like IL-6 are associated with atherosclerosis. Statins have pleiotropic effects, including anti-inflammatory properties, and may reduce atherosclerosis. Anti-inflammatory treatments like methotrexate and biologics may benefit CVD. Monoclonal antibodies against oxLDL or PC may target atherosclerosis. HSP immunization shows potential in animal models. Anti-inflammatory therapies, including HSP-based treatments, are under investigation. Atherosclerosis is a chronic inflammatory process in arteries, with immune cells playing a key role. Inflammation triggers plaque rupture, leading to CVD. While the exact mechanisms are unclear, inflammation is a major contributor to atherosclerosis. Treatments targeting inflammation and immune responses are being explored to prevent or treat CVD.Atherosclerosis, the leading cause of cardiovascular disease (CVD), is a chronic inflammatory condition involving immune cells producing pro-inflammatory cytokines. Oxidized low-density lipoprotein (oxLDL) plays a key role, as it is immunogenic, toxic, and contains inflammatory phospholipids with phosphorylcholine (PC) as an epitope. Antibodies against PC may protect against atherosclerosis by reducing inflammation. While bacteria and viruses have been implicated, direct evidence is limited. Heat shock proteins (HSPs) may be targets for immune reactions. Pro-inflammatory cytokines, chemokines, and lipid mediators contribute to plaque rupture. Clinical studies are needed to confirm inflammation's role in atherosclerosis. OxLDL activates endothelial cells, monocytes/macrophages, and T cells, and is toxic at high concentrations. Inflammatory phospholipids like lysophosphatidylcholine (LPC) mimic oxLDL's effects. OxLDL also generates damage-associated molecular patterns (DAMPs), such as malondialdehyde (MDA), which induce inflammation. Dead cells in atherosclerosis can activate the innate immune system, releasing IL-1β and activating the inflammasome. Anti-PC antibodies may reduce atherosclerosis by inhibiting oxLDL uptake and inflammation. HSPs, particularly HSP60, are immunogenic and may contribute to atherosclerosis. Infections like Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus have been linked to atherosclerosis, but evidence is inconclusive. Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is converted to trimethylamine-N-oxide (TMAO), accelerating atherosclerosis. Infections may indirectly promote atherosclerosis by stimulating inflammation. Inflammatory markers like C-reactive protein (CRP) and cytokines like IL-6 are associated with atherosclerosis. Statins have pleiotropic effects, including anti-inflammatory properties, and may reduce atherosclerosis. Anti-inflammatory treatments like methotrexate and biologics may benefit CVD. Monoclonal antibodies against oxLDL or PC may target atherosclerosis. HSP immunization shows potential in animal models. Anti-inflammatory therapies, including HSP-based treatments, are under investigation. Atherosclerosis is a chronic inflammatory process in arteries, with immune cells playing a key role. Inflammation triggers plaque rupture, leading to CVD. While the exact mechanisms are unclear, inflammation is a major contributor to atherosclerosis. Treatments targeting inflammation and immune responses are being explored to prevent or treat CVD.