## Mechanism of Statin Action **Key Point:** Statins lower LDL cholesterol primarily through two mechanisms: (1) inhibition of HMG-CoA reductase, and (2) upregulation of hepatic LDL receptors. ### Correct Mechanisms | Mechanism | Effect | Clinical Significance | |-----------|--------|----------------------| | HMG-CoA reductase inhibition | Reduced intracellular cholesterol synthesis | Primary effect; ~30% LDL reduction | | LDL receptor upregulation | Increased hepatic uptake of LDL-C | Synergistic; additional ~20% reduction | | Reduced VLDL production | Fewer VLDL particles secreted; fewer LDL remnants | Secondary benefit | ### Why Option 3 (Lipoprotein Lipase) Is Wrong **High-Yield:** Statins do NOT inhibit lipoprotein lipase. Lipoprotein lipase is the enzyme responsible for hydrolysis of triglycerides in chylomicrons and VLDL in the capillary endothelium. This enzyme is inhibited by **fibrates** (e.g., gemfibrozil), not statins. **Clinical Pearl:** Statins work at the hepatic level (cholesterol synthesis and receptor expression), whereas fibrates work at the peripheral level (triglyceride hydrolysis). This is why fibrates are preferred for hypertriglyceridemia, and statins for LDL reduction. **Mnemonic:** **STATIN** = **S**ynthesis (HMG-CoA reductase) + **T**ransport (LDL receptors). **FIBRATE** = **F**at (triglycerides) + **I**ntestinal/peripheral lipase. [cite:KD Tripathi 8e Ch 31]
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