Biochemie der Ernährung | Prof. Dr. Stefan Lorkowski - Pathogenese der Arteriosklerose

Biochemie der Ernährung

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Prof. Dr. Stefan Lorkowski

 

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Biochemie der Ernährung  >>  Institut für Ernährungswissenschaften  >>  Friedrich-Schiller-Universität Jena

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Pathogenese der Arteriosklerose

 

 

Atherosclerosis is an inflammatory disease of the inner wall of large and medium-sized arteries, including the aorta, the carotid arteries, the coronary arteries and the arteries of the lower extremities. The earliest lesions of atherosclerosis appear during infancy but it usually takes several decades to develop the full-blown atherosclerotic plaque, which is characterized by a large necrotic lipid core covered by a thin fibrous cap consisting of extracellular matrix proteins such as collagen, and small numbers of matrix-producing smooth muscle cells.

 

 

Endothelial dysfunction

 

The “response-to-injury hypothesis”, first proposed by the Viennese pathologist Karl von Rokitansky in the mid 19th century and rediscovered in 1973 by the American pathologists Russell Ross and John A. Glomset, is the model that is most widely used to explain the appearance of atherosclerosis. According to this hypothesis, atherosclerosis begins with injury to the endothelium caused by chemical, mechanical, or immunological factors. More recent work, however, emphasizes a dysfunction rather than an injury of the endothelium as the trigger of atherosclerosis. It is thought that such endothelial dysfunction may be caused by modified lipoproteins from the blood, free radicals, toxic substances, high blood pressure, diabetes mellitus, infectious agents such as herpes viruses or Chlamydia pneumonia, or by a combination of these factors.

 

Endothelial dysfunction

 

  

Adhesion of blood cells

 

Endothelial dysfunction is characterized by a loss of endothelial-derived vasodilation, endothelial activation, and increased permeability of the endothelial barrier. The impairment of vasodilatation is a consequence of a reduced bioavailability of vasodilators, in particular nitric oxide, and an increase in endothelium-derived vasoconstrictors such as endothelin. Activation of the endothelium is characterized by a pro-inflammatory, proliferative and pro-coagulatory state, which is accompanied by an increased expression of adhesive glycoproteins such as P-selectin and E-selectin and of adhesion molecules such as vascular cell-adhesion molecule 1 (VCAM-1) and intracellular cell-adhesion molecule 1 (ICAM-1). These in turn promote the adhesion of leukocytes (in particular monocytes and T lymphocytes) and thrombocytes to the arterial wall.

 

Adhesion of leukocytes and thrombocytes

 

 

Immigration of adhered white blood cells

 

As a consequence, adherent monocytes migrate into the subendothelial space by a process called diapedesis under the influence of inflammatory and chemoattractant molecules, in particular the chemokine macrophage chemoattractant protein-1 (MCP-1) and other mediators such as interleukin 8. These monocytes differentiate into macrophages, which accumulate within the subendothelial tissue. Macrophages constitute an ancient part of our immune system and express a number of scavenger receptors such as scavenger receptor A, scavenger receptor B1 (SR-B1), and cluster of differentiation (CD) 36 and CD68 on their surface. These proteins recognize polyanionic macromolecules and may have physiological functions in the recognition and clearance of pathogens and apoptotic cells.

 

Immigration of adhered white blood cells

 

 

Immigration of smooth muscle cells and foam cell formation

 

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Immigration of smooth muscle cells and foam cell formation

 

 

Adapted from

Lorkowski & Cullen. Atherosclerosis. Encyclopedia of Life Sciences 2006.

 

 

 

Übersicht

 

  Hintergrund
  Arteriosklerose
 

Arterien

 

Adaptive Verdickung

 

Pathogenese

  Makrophagen

 

 

 

 

 

 

 

 

 

 

 

Institut für Ernährungswissenschaften

Friedrich-Schiller-Universität Jena
Dornburger Str. 25
07743 Jena
 

+49 3641 9-49710

+49 3641 9-49712

 

bce [at] uni-jena.de

 

 

 

 

 

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Stefan Lorkowski | 2008-2010

 

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