Early Human Atherosclerosis

TLDR

The study aims to clarify the morphological features of early human atherosclerosis and assess the role of specific extracellular matrix proteoglycans in its initiation. The authors examined serial sections of right coronary arteries without or with early atherosclerosis, classifying lesions into four grades based on lipid deposition. Early lesions show diffuse intimal thickening with biglycan and decorin in the outer layer; as lipid deposition increases, fatty streaks form with these proteoglycans, macrophages infiltrate deeper, and advanced lesions develop pathologic intimal thickening with foam cells beneath lipid layers.

Abstract

Objective— The present study was designed to clarify the morphological features of early human atherosclerosis and to determine whether specific extracellular matrix proteoglycans play a role in early atherogenesis. Methods and Results— Step and serial sections were obtained from right coronary arteries with no or early atherosclerosis. Atherosclerosis was classified into 4 grades according to the amount of lipid deposition. Coronary arteries with Grade 0 showed diffuse intimal thickening (DIT) with no lipid deposits. The extracellular matrix proteoglycans, biglycan and decorin, were localized in the outer layer of DIT. Most cases of Grade 1 and Grade 2 exhibited fatty streaks with extracellular lipids colocalizing with biglycan and decorin in the outer layer of the intima. As lipid grades increased, macrophages increased in number and were present in the deeper layers. Most cases of Grade 3 exhibited pathologic intimal thickening (PIT) with extracellular lipids underneath a layer of foam cell macrophages. Conclusions— In early human coronary atherosclerosis, fatty streaks develop via extracellular deposition of lipids associated with specific types of proteoglycans in the outer layer of preexisting DIT. As the amount of the lipid increases in fatty streaks, macrophages infiltrate toward the deposited lipid to form PIT with foam cells.