**5. Conclusions**

*Apolipoproteins, Triglycerides and Cholesterol*

process is the main cause of acute cardiovascular events.

the disease and largely avoid cardiovascular endpoint events [32].

Familial hypercholesterolemia is an autosomal dominant genetic disease characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) and premature coronary heart disease, mainly caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase

**4.2 Congenital defect: familial hypercholesterolemia (FH)**

Most of the atherosclerotic lesions caused by functional disorders progress slowly, and the clinical symptoms appear relatively late, which is mainly due to the existence of a series of compensation mechanisms, from the molecular level to the organ level, forming the natural defense line of the body. The breakthrough of the line of defense is characterized by micro decompensation, which corresponds to the progress of the disease at the macro level. The occurrence of cardiovascular events represents the loss of the ability to maintain stability, and treatment such as stenting can quickly relieve symptoms. However, this does not solve problems fundamentally, and it is necessary to effectively control the concentration of LDL particles having atherogenic properties. Combined with clinical experience, controlling the level of circulating LDL-C is the only effective method at present. Fortunately, the basic physiological processes of these patients are complete, and their regulatory network still exists. The focus of treatment is on using drugs to help the body to build a new balance. On the basis of a healthy lifestyle, adequate statin administration is effective in controlling LDL-C levels. For patients with moderate- or high-dose statin intolerance, the use of statins can be reduced by combining with ezetimibe or proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitors, which can delay or even prevent the progression of

cytokines, realizing cross-dialog between different immune cell groups and initiating adaptive immunity. All the mechanisms work together to launch a sharp attack on ox-LDL, forming a chronic inflammatory process unique to atherosclerotic diseases [27]. The persistent inflammatory response stimulates smooth muscle cells to migrate to the intima-media, proliferate, and secrete large amounts of collagen, and the lesion enters the fibrous plaque stage. In this stage, intima thickening and remodeling first lead to increasing arterial wall stiffness and increased interfacial pressure in the environment where LDL is located, which promotes secondary structural changes of apoB-100 [28]. Secondly, the ability of regional oxygen diffusion was weakened, and the intermediate area of atherosclerotic lesions and intima-media showed ischemia and hypoxia. For the purpose of compensation, glycolysis becomes the primary mode of cell productivity in this region. This metabolic process produces lactic acid, which leads to extracellular space acidification. The state of regional low PH value is beneficial to the activation of macrophages and the upregulation of ox-LDL receptor (mainly LOX-1) expression in macrophages. The upregulated LOX-1 increases the lipid absorption of macrophages and promotes the formation of foam cells [29]. In addition, upregulated LOX-1 increases endothelial permeability and promotes the migration of ox-LDL to subendothelial space by reducing the expression of desmoglein-1 (DSG-1) and desmocollin-2 (DSC-2) [30, 31]. Under the stimulation of ox-LDL, the above process is repeated, the fiber cap becomes thickened, the declining foam cells form a necrotic lipid core, and the lesion enters the atherosclerotic plaque stage. When the compensatory arterial dilatation is unable to compensate for the stenosis caused by plaques protruding into the lumen, blood flow changes. The clinical manifestation is stable coronary syndrome. After that, if the disease continues to evolve, under the action of mechanical stimulation or inflammatory mediators, the fibrous cap becomes thinner, and local macrophages are activated, followed by focal necrosis, plaque rupture, content flow out, and thrombosis. The initiation of this

**164**

LDL participates in the whole process of the formation and development of atherosclerotic lesions in the form of mLDL until plaque rupture, thrombosis, and cardiovascular events occur. The understanding of the characteristics of atherosclerosis caused by LDL should be built on the understanding of individual context. At present, a single LDL-C level has been impossible to accurately predict the progression of atherosclerotic lesions. The application value of mLDL, sd-LDL, etc. in the clinical practice needs to be further explored in the future.
