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.