Atherosclerosis - Wikipedia
Hypercholesterolemia and atherosclerosis change vascular reactivity in rabbits by different Mar Arteriosclerosis and Thrombosis: A Journal of Vascular Biology. After 2 months, the only difference was an enhancement of contractile . Mechanisms of hypercholesterolemia and atherosclerosis. overloading with cholesterol and saturated fat in the rabbit results in early atherosclerotic lesions. In general, an inverse relationship is observed between LDLR activity and serum .
These plaques usually produce the most damage to the individual when they rupture. Cholesterol crystals may also play a role. The fibrous plaque contains collagen fibers eosinophilicprecipitates of calcium hematoxylinophilic and, rarely, lipid-laden cells. In effect, the muscular portion of the artery wall forms small aneurysms just large enough to hold the atheroma that are present.
The muscular portion of artery walls usually remain strong, even after they have remodeled to compensate for the atheromatous plaques. However, atheromas within the vessel wall are soft and fragile with little elasticity. Arteries constantly expand and contract with each heartbeat, i. In addition, the calcification deposits between the outer portion of the atheroma and the muscular wall, as they progress, lead to a loss of elasticity and stiffening of the artery as a whole.
The calcification deposits,  after they have become sufficiently advanced, are partially visible on coronary artery computed tomography or electron beam tomography EBT as rings of increased radiographic density, forming halos around the outer edges of the atheromatous plaques, within the artery wall. These deposits demonstrate unequivocal evidence of the disease, relatively advanced, even though the lumen of the artery is often still normal by angiography.
Rupture and stenosis[ edit ] Progression of atherosclerosis to late complications. Although the disease process tends to be slowly progressive over decades, it usually remains asymptomatic until an atheroma ulcerateswhich leads to immediate blood clotting at the site of atheroma ulcer. This triggers a cascade of events that leads to clot enlargement, which may quickly obstruct the flow of blood.
A complete blockage leads to ischemia of the myocardial heart muscle and damage. This process is the myocardial infarction or "heart attack". If the heart attack is not fatal, fibrous organization of the clot within the lumen ensues, covering the rupture but also producing stenosis or closure of the lumen, or over time and after repeated ruptures, resulting in a persistent, usually localized stenosis or blockage of the artery lumen.
Repeated plaque ruptures, ones not resulting in total lumen closure, combined with the clot patch over the rupture and healing response to stabilize the clot is the process that produces most stenoses over time.
The stenotic areas tend to become more stable despite increased flow velocities at these narrowings. Most major blood-flow-stopping events occur at large plaques, which, prior to their rupture, produced very little if any stenosis.
Most severe clinical events do not occur at plaques that produce high-grade stenosis. These tissue fragments are very clot-promoting, containing collagen and tissue factor ; they activate platelets and activate the system of coagulation.
The result is the formation of a thrombus blood clot overlying the atheroma, which obstructs blood flow acutely. With the obstruction of blood flow, downstream tissues are starved of oxygen and nutrients. If this is the myocardium heart muscle angina cardiac chest pain or myocardial infarction heart attack develops.
Accelerated growth of plaques[ edit ] The distribution of atherosclerotic plaques in a part of arterial endothelium is inhomogeneous. The multiple and focal development of atherosclerotic changes is similar to that in the development of amyloid plaques in the brain and that of age spots on the skin.
Misrepair-accumulation aging theory suggests that misrepair mechanisms   play an important role in the focal development of atherosclerosis. Because of the infusion of lipids into sub-endothelium, the repair has to end up with altered remodeling of local endothelium. This is the manifestation of a misrepair. Important is this altered remodeling makes the local endothelium have increased fragility to damage and have reduced repair-efficiency.
As a consequence, this part of endothelium has increased risk to be injured and to be misrepaired. Thus, the accumulation of misrepairs of endothelium is focalized and self-accelerating. In this way, the growing of a plaque is also self-accelerating. Within a part of arterial wall, the oldest plaque is always the biggest, and is the most dangerous one to cause blockage of local artery.
Components[ edit ] The plaque is divided into three distinct components: Atherosclerotic lesions, or atherosclerotic plaques, are separated into two broad categories: Stable and unstable also called vulnerable.
On the other hand, unstable plaques are rich in macrophages and foam cellsand the extracellular matrix separating the lesion from the arterial lumen also known as the fibrous cap is usually weak and prone to rupture.
Upon formation, intraluminal thrombi can occlude arteries outright e. Apart from thromboembolism, chronically expanding atherosclerotic lesions can cause complete closure of the lumen. These complications of advanced atherosclerosis are chronic, slowly progressive and cumulative.
Familial Hypercholesterolemia and the Atherosclerotic Disease
Most commonly, soft plaque suddenly ruptures see vulnerable plaquecausing the formation of a thrombus that will rapidly slow or stop blood flow, leading to death of the tissues fed by the artery in approximately five minutes. This event is called an infarction. Diagnosis[ edit ] Microphotography of arterial wall with calcified violet color atherosclerotic plaque hematoxylin and eosin stain Areas of severe narrowing, stenosisdetectable by angiographyand to a lesser extent " stress testing " have long been the focus of human diagnostic techniques for cardiovascular diseasein general.
However, these methods focus on detecting only severe narrowing, not the underlying atherosclerosis disease. As demonstrated by human clinical studies, most severe events occur in locations with heavy plaque, yet little or no lumen narrowing present before debilitating events suddenly occur. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility and sometimes sudden death.
Plaques that have ruptured are called complicated plaques. The extracellular matrix of the lesion breaks, usually at the shoulder of the fibrous cap that separates the lesion from the arterial lumen, where the exposed thrombogenic components of the plaque, mainly collagen will trigger thrombus formation.
Mechanisms of hypercholesterolemia and atherosclerosis.
The thrombus then travels downstream to other blood vessels, where the blood clot may partially or completely block blood flow. If the blood flow is completely blocked, cell deaths occur due to the lack of oxygen supply to nearby cells, resulting in necrosis. The narrowing or obstruction of blood flow can occur in any artery within the body.
Obstruction of arteries supplying the heart muscle results in a heart attackwhile the obstruction of arteries supplying the brain results in an ischaemic stroke. The majority of cardiovascular events that involve sudden rupture of the atheroma plaque do not display any evident narrowing of the lumen. Thus, greater attention has been focused on "vulnerable plaque" from the late s onwards. Some of the detection approaches include anatomical detection and physiologic measurement.
Examples of anatomical detection methods include coronary calcium scoring by CT, carotid IMT intimal media thickness measurement by ultrasound, and intravascular ultrasound IVUS. Examples of physiologic measurement methods include lipoprotein subclass analysis, HbA1chs-CRPand homocysteine. Both anatomic and physiologic methods allow early detection before symptoms show up, disease staging and tracking of disease progression.
Other factors are generally of lesser importance. Severe dietary overloading with cholesterol and saturated fat in the rabbit results in early atherosclerotic lesions resembling almost totally those produced by the genetic absence of LDL-receptors Watanabe rabbit.
In humans from western countries the serum LDL-level is more related to environmental factors, whereas the HDL-level is more related to genetic factors. Age is an important factor integrating the effects of genetics and environmental deviations.
The influence of sex is also important. Serum cholesterol in western countries is increasing markedly with age, but this growth of serum cholesterol with age is totally different between sexes. Serum cholesterol is on the average only equal in both sexes at ages 3, 10, 25 and It is higher in males between ages 25 and 50 and higher in females between ages 3 to 10, 10 to 25 and above 50 years. In general females are less susceptible to higher cholesterolemia than males except at very old ages above years.
Together with other observations of sex linked differences this points to the influence of a sex linked chromosome, most probably the X-chromosome.