Cholesterol crystals, smooth muscle cells and new data on the genesis of atherosclerosis

The histologic appearance of atherosclerosis has been well described but its pathogenesis is still vigorously debated. The purpose of the present study is to clarify the stimuli for smooth muscle cells (SMC) migration and proliferation as well as the way of cholesterol crystals (CC) generation. We performed postmortem ultrastructural analysis of myocardial samples obtained from 45 patients (33 males, 12 females, age range 18-85) who died from different diseases, mainly from acute myocardial infarction-MI (37 cases). Tissue was taken by transthorax express-necropsy method immediately after patients' death in the clinic. In myocardial infarction cases intact zones of the heart were examined. We have found a few foci of modified SMC proliferation in the periarteriolar space around necrotic cellular debris in elder patients. Lymphocytes, myofibroblasts and some leukocytes infiltrated those areas. The modified SMC phagocyted necrotic material and formed secondary lysosomes, inside which from one to three CC originated. In parallel with the reduction of necrotic mass inside the lysosomes, CC size increased. In the final phase the CC were discharged from the SMC into the interstitium. After exocytosis a tendency for the CC to accumulate was observed. They formed clusters consisting of 20-30 crystals. Most of the CC were of typical needle-like or rhomboid shape. Modified SMC were producing not only CC but also collagen and elastin. This study indicates that atherosclerotic process in the myocardium is connected with the appearance of modified SMC inside which CC are generated.