Research Area

Atherosclerosis


Introduction of atherosclerosis

Atherosclerosis is the most common type of vascular disease; it starts from the lesion of intima. Generally, there are lipid and complex carbohydrate accumulation, hemorrhage and thrombosis, fibrous tissue hyperplasia and calcinosis, and gradual metamorphosis and calcification of the middle layer of the artery. The lesion often involves large and medium muscular arteries, once developed enough to block the arterial lumen, the tissue or organ supplied by the artery will be ischemic or necrotic. Atherosclerosis is the most common and important disease in atherosclerotic vascular disease. It is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases such as coronary atherosclerotic heart disease (CHD) and cerebrovascular disease. Among them, cardiovascular disease is the main cause of death worldwide, and the most influential is atherosclerotic cardiovascular disease. Atherosclerosis is a progressive pathophysiological process involving multiple factors, always accompanied by inflammatory cell infiltration and the involvement of a large number of inflammatory factors. Studies have shown that atherosclerotic lesions begin in the intima, and lipid spots and lipid streaks appear successively in the intima of the affected arteries, followed by atheromatous plaques and fibrotic plaques and complex lesions. Inflammatory factors, high shear stress, and macrophage death can cause plaque instability and rupture, leading to platelet aggregation, adhesion and thrombosis, sudden interruption of blood flow, and acute cardiovascular events. In the process of the development and progression of atherosclerosis, a variety of complex factors are intertwined and promoted. There have been many theories to explain its pathogenesis from different angles. Earlier, there is lipid infiltration theory, thrombosis theory, hemodynamics theory, smooth muscle cell cloning theory, etc., but they are not perfect. In 1976, Ross proposed the theory of endothelial injury response. It is believed that atherosclerotic lesions are the result of excessive inflammation-fibroproliferative response of arteries to various factors causing endothelial and vascular wall smooth muscle injury. The process has a large number of growth factors and inflammatory factors. And vascular regulatory molecules are involved. In recent years, with the development of molecular biology and genomics and other technologies, a more comprehensive and in-depth study on the pathogenesis of atherosclerosis has emerged, resulting in a variety of new theories, which explain from the perspective of inflammation and immunity, oxidative stress, and genetics.

The mechanism of atherosclerosis

Since Ross proposed atherosclerosis is a chronic inflammatory disease that has been widely recognized in academia. The research mainly focuses on inflammatory cells, cytokines, adhesion molecules, and the interaction of oxidative stress and immune mechanisms. It is currently believed that inflammation and immunity are the most important mechanisms of atherosclerosis and participate in all stages of the development of lesions. During atherosclerosis, mononuclear macrophages, T lymphocytes, B lymphocytes, dendritic cells, neutrophils, natural killer cells, and related cytokines take part in this process. The barrier function of the arterial endothelium is impaired by various factors, and the chemokines and cytokines that mediate monocyte adhesion. After that, the permeability of the endothelium is increased, and the low-density lipoprotein cholesterol (LDL-C) in the blood enters the endometrium and accumulates under the endometrium, which is a key initial step in the development of atherosclerosis. According to previous studies, T lymphocytes are widely present in atherosclerotic lesions. Monocytes and T cells adhere to the surface of the damaged vascular endothelium and enter the endothelium, marking the beginning of early inflammation of atherosclerotic plaque formation. B lymphocytes are only detected in small amounts in atherosclerotic lesions, mainly in the adventitia surrounding the lesion, regulating the inflammatory response in the lesion. Its function is still unclear. Dendritic cells are the most powerful professional antigen presenting cells in the body, which submits an antigen to present T lymphocytes and B lymphocytes to complete the immune response in the development of atherosclerosis. Neutrophil cells play an important role in the formation of atherosclerosis and plaque rupture. It enhances the inflammatory response by accumulating adhesion of other white blood cells, enhancing antigen presentation and other functions. The persistent inflammatory response eventually leads to plaque instability and rupture. In addition, natural killer cells are also found to affect atherosclerosis in some animal model experiments, but the specific role is still controversial and needs further study.

In addition to the effects of inflammatory reactions, the damage caused by the active oxygen free radicals that cannot be removed by the body when exposed to harmful stimuli is also one of the important mechanisms of atherosclerosis. In addition, studies have shown that epigenetic regulation is also involved in the development of atherosclerosis.

Clinical significance

Cardiovascular and cerebrovascular diseases are one of the major diseases currently affecting human health and quality of life. Atherosclerosis is one of the important causes of cardiovascular and cerebrovascular diseases. The cause may be caused by hypertension, diabetes, hyperlipidemia and obesity, or bad habits such as smoking and unreasonable diet. Clinically, lipid-lowering drugs and anti-platelet drugs are mainly used to treat atherosclerosis. However, they have some problems: 1. The function of blocking the substances required for normal physiological function; 2. These drugs cause great damage to liver and kidney function, and long-term use will inevitably cause liver and kidney diseases. At present, treatment is mainly based on prevention and delay, reasonable diet and moderate exercise are beneficial to control and alleviate the progression of atherosclerosis.

References:

  1. Sakakura K, et al.Pathophysiology of atherosclerosis plaque progression. Heart Lung Circ. 2013, 22(6): 399-411.
  2. Moore KJ,Tabas I. Macrophages in the pathogenesis of atheroselerosis.Cell. 2011, 145(3): 341-355.
  3. Ross R.The pathogenesis of atherosclerosis: aperspective for the 1990s. Nature. 1993, 362(6423): 801-809.
  4. Ross R.Atherosclerosis~an inflammatory disease. N Engl J Med. 1999,340(2): 115-126.
  5. Tsiantoulas D, et al.B cells and humoral immunity in atherosclerosis.Circ Res. 2014, 1 14(11):1743-1756.
  6. Mitra S, et al.Oxidized low-density lipoprotein and atherosclerosis implications in antioxidant therapy. Am J Med Sci. 2011, 342(2):135-142.
  7. Seneviratne AN, et al. Troll-like receptors and macmphage activation in atherosclerosis. Clin chim Acta. 2012, 413(1-2): 3-14.
  8. Soehnlein O. Multiple roles for neutrophils in atherosclemsis. Circ Res. 2012, 110(6): 875-888.

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