INTRODUCTION
Atherosclerosis is caused by a buildup of cholesterol in the inner lining of the artery wall, which causes inflammation and recruitment of immune cells in the blood arteries, thereby increasing the formation of atherosclerotic plaque (Tabas and Bornfeldt, 2020).
Atherosclerosis is a pathological process of coronary, cerebral, iliac and femoral arteries, and aorta that can lead to cardiovascular, cerebrovascular, and peripheral arterial disease. Sometimes, coronary artery narrowing is sufficient to elicit ischemia discomfort, but not infarction, particularly during physical exercise (angina). In approximately one-third of instances of coronary heart disease, coronary artery blockage results in a deadly arrhythmia (sudden cardiac death) within minutes or hours(Yanik et al., 2000). These syndromes (angina pectoris, myocardial infarction, and sudden cardiac death) are all atherosclerosis-related cardiovascular illnesses. The angina-like episodes mentioned above suggest a high risk for cerebral infarction (stroke) in the patient. Stroke is a clinical state of neurological impairment induced by cerebral infarction produced by thrombus development on atherosclerotic plaques or brain tissue loss caused by artery rupture and bleeding(Yanik et al., 2000). A transient ischemic attack (TIA) is a transitory neurological impairment resulting from a blood clot develops on atherosclerotic plaque in the cerebral arteries and inadequate blood flow to the cerebral arteries(McIvor et al., 1994). Cerebral hemorrhage, which comprises cerebral hemorrhage (bleeding into the brain) and subarachnoid hemorrhage(Montaño et al., 2021), is another kind of stroke. This form of stroke is nearly often accompanied by severe hypertension, which is a key risk factor for cerebral infarction and cerebral hemorrhage because it exacerbates cerebral atherosclerosis(Li et al., 2017). Peripheral arterial disease is atherosclerosis of the abdominal aorta, iliac arteries, femoral arteries and mesenteric arteries and its complications. Atherosclerosis of the lower limb can lead to temporary arterial insufficiency of the lower extremities during exertion (intermittent claudication) or avascular necrosis of the extremities (gangrene)(Guan et al., 2018). In the abdominal aorta, the mediator under the atherosclerotic plaque deteriorates, causing an aneurysm that may fill with thrombus or explode into the abdominal cavity(De Waele et al., 2009). If the mesenteric blood supply arteries caused by atherosclerotic vascular stenosis occlusion occurs, it could cause atheroscle rotic non occlusive mesenteric ischemia, then the intestinal wall ischemic necrosis syndrome caused by blood supply disorder occurs. (Tan VP et al., 2013)In addition, gastrointestinal function is also affected by mesenteric blood supply. Mesenteric insufficiency caused by mesenteric atherosclerosis has become one of the important reasons leading to gastrointestinal function decline in the elderly.
Cholesterol and lipoproteins play crucial roles in atherosclerosis development. Atherosclerotic lesions begin with endothelial cell dysfunction, resulting in alteration of apoB-containing lipoproteins (low-density lipoprotein LDL, very low-density lipoprotein VLDL, remnants) and influx of immune cells(notably monocytes) into the subendothelial region(Feinberg and Jain, 2005; Getz and Reardon, 2018). Macrophages not only internalize retained apoB-containing lipoproteins into foam cells that produce fatty streaks,but it inflammatory pathways are also engaged, leading to increased oxidative stress and cytokine/chemokine release(Tirunavalli et al., 2021), leading to greater LDL/residual oxidation, endothelial cell activation, monocyte recruitment, and foam cell generation. HDL, apoA-I, and endogenous apoE limit lesion development by inhibiting endothelial cell activation, inflammation and oxidative stress, and facilitating cholesterol efflux from foam cells(De Geest et al., 1997). Persistent inflammation results in the transformation of lesions into fibrotic plaques, while macrophage chemoattractants increase the infiltration and proliferation of smooth muscle cells. The extracellular matrix produced by smooth muscle cells forms a persistent fibrous barrier between plaque prothrombotic components and platelets(Linton et al., 2000) Rupture of the thinning fibrous cap increases thrombosis, resulting to ischemic cardiovascular clinical outcomes(Shah, 2014). Infiltration, retention, and accumulation of lipoproteins in the artery intima have been demonstrated to induce a maladaptive immunological response that influences the genesis, progression, and stability of atherosclerotic lesions(Nakashima et al., 2008). The presence of high levels of modified cholesterol, particularly ox-LDL, is a major risk factor for the development of atherosclerosis. In atherosclerotic plaques, macrophages absorb ox-LDL, resulting in macrophages high in cholesterol, also known as foam cells(Gao et al., 2019). Foam cells contribute to plaque pathogenesis by generating matrix metalloproteinases (MMPs) that breakdown plaque extracellular matrix and by secreting various pro-inflammatory cytokines and chemokines. Atherosclerosis is a chronic lipid-driven arterial inflammatory disease in which cholesterol-rich lipoproteins, particularly LDL(Malekmohammad et al., 2021), accumulate subendothelially in vulnerable artery wall locations, provoking leukocyte infiltration.
Here, how lipids and oxidative stress participate in atherosclerosis via immunometabolism has been reviewed and discussed. As well, main herbal medicines have been summarized in prevention and treatment of this pathological process using integrated Traditional Chinese and Western Medicine. This work will provide a basis for therapy optimization of atherosclerosis from the perspective of lipid and oxidative stress-associated immunometabolism.