s4

• Serum cholesterol levels and CHD in men without established CHD
• The INTERHEART Study - Most important risk factors in 52 countries
• Fatty streak, Large atheroma with thrombus
• Circulating LDL gains access to subendothelial space where it is oxidised. Cytokines IL-1 and MCP-1 attract circulating monocytes that cross intima to become macrophages. The macrophages phagocytose LDL to form Foam Cells. Smooth muscle cells migrate and proliferate under the influence of smooth muscle mitogens. A primitive plaque is formed of Foam Cells, Smooth muscle, Lipid & necrotic cells. The plaque enlarges, develops a fibrous capsule and protrudes in vessel lumen.
• Mechanism: Reduction in receptor mediated clearance of LDL Due to mutation of LDLR, APOB or PCSK9 gene. Prevalence: 1 in 250. Lipid Profile: Elevated LDL-cholesterol, TC 9-12mmol/L, Low normal fasting triglycerides. Inheritance: Autosomal co-dominant. Physical Signs: Tendon Xanthomas, corneal arcus. Homozygotes – also planar digital and natal cleft cutaneous xanthomas, aortic stenosis. CHD risk: Very high (symptomatic in 50% of males by age 50, 50% of females by age 60)
• It is an essential component of all animal cell membranes. It is an important precursor in steroid synthesis. It is an important component of bile. It is synthesised by all animal cells. It is found in low levels in the gall bladder.
• Drug Targets