How do PCSK9 inhibitors lower LDL-C?

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Multiple Choice

How do PCSK9 inhibitors lower LDL-C?

The main idea is that PCSK9 inhibitors increase the liver’s capacity to clear LDL cholesterol by keeping LDL receptors on the hepatocyte surface. PCSK9 normally binds to LDL receptors and directs them to be degraded, so fewer receptors are available to pull LDL particles from the blood. When PCSK9 is inhibited, these receptors are recycled back to the cell surface instead of being destroyed, so there are more receptors to bind and internalize LDL. The result is enhanced hepatic uptake of LDL-C and lower plasma LDL-C levels. This mechanism is distinct from altering intestinal cholesterol absorption, raising VLDL production, or changing lipoprotein lipase activity, which is why the inhibitor’s effect is specific to increasing LDL receptor–mediated clearance.

The main idea is that PCSK9 inhibitors increase the liver’s capacity to clear LDL cholesterol by keeping LDL receptors on the hepatocyte surface. PCSK9 normally binds to LDL receptors and directs them to be degraded, so fewer receptors are available to pull LDL particles from the blood. When PCSK9 is inhibited, these receptors are recycled back to the cell surface instead of being destroyed, so there are more receptors to bind and internalize LDL. The result is enhanced hepatic uptake of LDL-C and lower plasma LDL-C levels. This mechanism is distinct from altering intestinal cholesterol absorption, raising VLDL production, or changing lipoprotein lipase activity, which is why the inhibitor’s effect is specific to increasing LDL receptor–mediated clearance.

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