Atherosclerosis refers to the growth and development of fatty streaks on the innermost lining of your blood vessels, such as your aorta and coronary arteries. Initially, these fatty streaks are focal, small, and non-obstructive. Thus, you will not experience any form of health disturbances at this stage. However, when these fatty streaks become large and obstruct the diameter of your blood vessels, such that blood flow is hindered, you will experience medical problems such as hypertension and ischemic heart disease (IHD). Both of these conditions could lead to stroke and myocardial infarction (heart attack), which could, in turn, lead to your possible death.
There are several theories which aim to explain the development of atherosclerosis.
Reaction to injury
Based on this theory, the endothelium which covers the inner lining of your blood vessels will be exposed to an injurious event. Examples of such injuries are metabolic, mechanical, and immunologic. A metabolic injury would be hypercholesterolemia or homocysteinemia, while mechanical stress is when there is added pressure on the veins from hypertension or due to a blunt force injury. The immunologic injury may be seen after cardiac or renal transplantation. When the endothelium around the vein is broken due to an injury, this will expose the next inner lining of your blood vessels, which is called the subendothelial tissue. When this tissue is exposed, the following events can take place:
-Monocytes, which are a type of white blood cell and platelets, become more adherent to the subendothelial tissue, hastening their deposition in that area.
-Migration of monocytes into the intima to become macrophages.
-Platelet aggregation and formation of microthrombi.
-The release of platelet and macrophage secretory products, including growth factors and cytokines (such as platelet-derived growth factor, interleukin 1, colony stimulating factors), in conjunction with plasma constituents, including lipoproteins and hormones such as insulin.
These events could stimulate the proliferation of intimal smooth muscle cells at these sites of injury. Proliferating smooth-muscle cells would then deposit a connective tissue matrix and accumulate lipid, a process that would be particularly enhanced when there are increased blood levels of cholesterol and/or triglycerides. Monocyte-derived macrophages can also accumulate lipids, some of which are in the form of lipid-protein complexes characteristic of oxidized lipoproteins. These cells are capable of modifying lipoproteins in situ, favoring their uptake by scavenger receptors. Endothelial cells and macrophages can elaborate a chemoattractant (with an ability to attract) protein that sustains accumulation of monocyte-derived macrophages.
A repeated or chronic injury could lead to a slowly progressing lesion involving a gradual increase in intimal smooth muscle cells, macrophages, connective tissue, and lipid. Areas where the shearing stress on endothelial cells is increased, such as branch points or bifurcation of vessels, would be at greatest risk. As the lesions enlarge and the intima becomes thicker, resistance to blood flow over the sites will increase and will potentially place the lining endothelial cells at even greater risk for further injury, leading to an inexorable cycle of events ending in the complicated lesion. The key point in this theory is that the injury must be sustained, chronic, and continuing so that the complications become irreversible and progressive. If the injurious episodes are few in number, single, and sporadic then proliferative response could still regress and prevention of complications could still be done. Generation of complications is prevented if the source, or sources, of injury are removed and remedied. This hypothesis of reaction to injury thus is consistent with and supportive to the known intimal thickening observed in normal aging. It would also explain that the causative factors implicated in atherogenesis might enhance lesion formation and explain how inhibitors of platelet aggregation could interfere with lesion formation. This would showcase risk-factor reduction treatments, can interrupt progression, or even produce regression of atheromatous lesions.
Monoclonal hypothesis
This theory suggests that intimal proliferation, which will lead to the development of atherogenic lesions, starts from a single cell. It means that a single cell misbehaves and multiplies like cells in benign tumors. Under this theory, it is possible that mitogenic or mutagenic factors work hand in hand to stimulate smooth muscle cell proliferation from single cells.
Clonal senescence
This theory describes how intrinsic aging processes contribute to atherosclerosis. In a healthy body, intimal smooth-muscle cells that proliferate to form an atheroma are under feedback control by mitosis inhibitors. When these inhibitors fail, then atherosclerosis can develop. Mitosis inhibitors are formed by the smooth muscle cells in the contiguous media. The feedback control system tends to fail with age, as these controlling cells die and are not adequately replaced. This is consistent with the observation that cultured human arterial medial smooth-muscle cells, like fibroblasts, show a decline in their ability to replicate as a function of donor age.
Lysosomal theory
Lysosomal theory suggests that altered lysosomal function might contribute to atherogenesis. Since lysosomal enzymes can accomplish the generalized degradation of cellular components required for continuing renewal, this system has been implicated in cellular aging and the accumulation of lipofuscin or “age pigment”. It has been suggested that increased deposition of cholesterol esters in arterial smooth-muscle cells may be related in part to a relative deficiency in the activity of lysosomal cholesterol ester hydrolase. Consonant with this idea, some patients with the rare cholesterol ester storage disease caused by a defect in lysosomal cholesterol ester hydrolase may have accelerated atherosclerosis. However, lipid droplets in foam cells are often cytoplasmic, rather than lysosomal, and this theory is now not widely held.
From the foregoing discussion, it can be gleaned that increased level of cholesterol is injurious to your endothelium—the innermost lining of your blood vessels. When your endothelium is injured, the next inner lining which is known as the subendothelium becomes more vulnerable to other stressors, leading to the development of atheromatous plaques, which decrease the opening and flexibility of your blood vessels, leading to hypertension and ischemic heart diseases.
