CD143 in the development of atherosclerosis

Area of Science:

• Cardiovascular Biology
• Vascular Pathology
• Immunohistochemistry

Background:

• CD143, also known as angiotensin-I-converting enzyme (ACE), plays a role in regulating local angiotensin and kinin concentrations.
• Angiotensin II (Ang II) is implicated in fibrogenesis and atherosclerosis development.
• Understanding CD143 distribution in the vascular tree is crucial for elucidating its role in cardiovascular diseases.

Purpose of the Study:

• To investigate the distribution of CD143 in atherosclerotic and non-atherosclerotic human vascular segments.
• To determine the cellular sources and localization of CD143 expression during atherosclerosis progression.
• To assess the relationship between CD143 expression, atherosclerotic stage, and localization.

Main Methods:

• Analysis of 230 human vascular specimens (aorta, coronary, carotid, brachial, renal, iliac, femoral arteries) from 80 patients, staged by AHA criteria.
• Utilized the APAAP technique with ten antibodies against human CD143 and controls.
• Examined native and formalin-fixed tissues to identify CD143 expression patterns.

Main Results:

• CD143 was primarily found in endothelial cells of adventitial arterioles in non-atherosclerotic segments.
• A significant accumulation of CD143 was observed in all stages of atherosclerotic lesions.
• De novo CD143 expression originated from subendothelial cells, macrophages, and foam cells, with neo-expression in microvessels of advanced lesions.

Conclusions:

• CD143 expression is upregulated early and extensively in atherosclerotic lesions, independent of location.
• The de novo expression of CD143 in the vascular wall, particularly by macrophages and foam cells, suggests a pathogenetic role.
• CD143's role in modulating local angiotensins makes it a potential target for pharmacological intervention in atherosclerosis.