ATHEROSCLEROSIS

A chronic inflammatory fibroproliferative response to sustained endothelial injury.

Pre-Lesional Phase
1. Endothelial Dysfuntion or Injury Exposure to Ox LDL, immune complexes, homocysteine, toxins, viruses etc. (a) Accumulation of modified lipoproteins (Lps) and lipid into subendothelial environment. (b) Endothelial activation into phagocytic phenotype: release chemoattractants and adhesion molecules on the luminal surface. (c) Smooth muscle cells (SMC) activated into secretory phenotype with the increase release of connective tissue matrix components which bind and trap modified Lps. (d) Monocytes attach to surface of Endothelial cell (EC) 2. Fatty Streak Monocytes migrate through endothelium and become activated into phagoytic macrophages, which scavenge modified Lps and matrix components with the accummulation of lipid and formation of form cells. 3. Fibro-Fatty Lesion Activated ECs, and macrophages releases growth factors that promote the proliferation of SMCs and their release of connection tissue components which enlarge the size of the lesion and levels of accumulated lipid. Endothelial cell dysfunction caused by cytotoxic levels of lipid, modified Lps and cytokines released from foam cells results in their reduced capacity to prevent thrombosis and control vasospasm. ie decreased production of prostacyclin and edothelial derived relaxation factor. Platelets bind to lesion and release more growth factors and vasoactive mediators. 4. Fibrous Plague Inflammatory T cells infiltrate the lesions and maintain the inflammatory response with resultant excessive formation of fibrous tissue. Further chemo attraction of monocytes results in accummulation of more macrophages, production of leukotrienes, super oxide and foam cell formation. Macrophages also migrate out of the lesion an expose the endothalial sublayer, which activates platelets and thrombosis. Advanced complicated fibrous lesions with fibrous cap over lesion may experience erosion, fissures, thrombosis and calcification. The ongoing presence of an inflammatory response results in the release of proteolytic hyrolyases, which degrade the connective

tissue cap exposing the disrupting plague contents leading to thrombosis. Coronary plague disruption with consequent platelet aggregation and thrombosis with or with out vasospasm is the most important mechanism responsible for progression into unstable angina pectoris, acute myocardial infarction and sudden death.

Courtesy of Health World