Low density lipoprotein
Most cholesterol is transported in the blood together with proteins, forming particles known as low-density lipoproteins or LDL. lipoproteins).
When the cell needs cholesterol for membrane synthesis, it produces LDL receptor proteins and inserts them into its plasma membrane. When cholesterol is captured, it passes to the lysosomes where cholesterol esters are hydrolyzed, giving rise to free cholesterol, which thus remains available to the cell for membrane biosynthesis.
If too much free cholesterol builds up in the cell, the cell stops both cholesterol synthesis and the synthesis of LDL receptor proteins, so the cell makes and absorbs less cholesterol.
This regulated pathway for cholesterol absorption is disturbed in some individuals who inherit faulty genes for the production of LDL receptor proteins, so their cells are unable to take up cholesterol from the blood. The resulting elevated blood cholesterol levels predispose these individuals to premature atherosclerosis, and most of them die at an early age from myocardial infarction as a consequence of coronary artery disease. The abnormality can be attributed to the LDL receptor, which may be absent or defective.
In atherosclerosis
Elevated levels of cholesterol in the LDL fraction ("LDL cholesterol") are strongly associated with the development of atherosclerotic disease. Various experimental models and systematic epidemiological observations do, in fact, support a causal role for LDL cholesterol in the initiation and progression of atherosclerosis.
However, scientific medical reality shows that no rigorously controlled clinical trial has ever shown conclusively that lowering LDL cholesterol can prevent cardiovascular disease or increase longevity.
It must be kept in mind that this is not the only risk factor associated with this disease, and that its medical management must be planned based on the individual global cardiovascular risk assessment of each patient.
Reverse cholesterol transport and foam cells
As mentioned at the outset, LDL is not physiologically involved in a net influx of cholesterol into tissues. However, under certain pathological circumstances, such as LDL hypercholesterolemia, arterial hypertension, diabetes mellitus or smoking, an exaggerated and unregulated delivery of cholesterol from chemically modified (oxidized) LDL to subendothelial macrophage cells develops, which when overwhelmed in its depuration capacity, in a process known as "reverse cholesterol transport" and mediated by high-density lipoproteins (HDL), degenerate into unstable cells, prone to inflammation and pathological cell death (necrosis). The accumulation of these macrophages overloaded with cholesterol, known as foam cells, determines the development of atherosclerotic plaques in the arterial wall, a defining pathological fact of atherosclerotic disease.
LDL cholesterol values
Currently, the most internationally accepted values for LDL cholesterol are those defined by the American Heart Association (AHA):
- less than 100 mg/dL
- Optimal level of LDL cholesterol, corresponding to a reduced level of risk for ischemic heart disease.
- 100 to 129 mg/dL
- LDL level close to optimal
- 130 to 159 mg/dL
- Frontierizo o limítrofe high-level LDL
- 160 to 189 mg/dL
- High level of LDL
- 190 mg/dL and above
- Excessively high level, increased risk of ischemic heart disease.
However, optimal LDL cholesterol levels must be determined after a thorough analysis of each patient's risk factors, an analysis that must be carried out by a medical specialist.