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

Biochemie der Ernährung


Prof. Dr. Stefan Lorkowski








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




Immigration of smooth muscle cells and foam cell formation



Adapted from

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









Adaptive Verdickung















Institut für Ernährungswissenschaften

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

+49 3641 9-49710

+49 3641 9-49712


bce [at]






@ §



Stefan Lorkowski | 2008-2010


  This site in Englisch