In class we talked about the formation of VLDL lipoproteins in the liver. The as

Question

In class we talked about the formation of VLDL lipoproteins in the liver.   The assembly of VLDL particles within the liver involves a protein called microsomal triglyceride transfer protein (MTP), which is essential for the assembly of apolipoprotein B (apo-B) containing lipoproteins. Known inhibition of MTP prevents hepatic VLDL secretion by preventing VLDL production. Given this effect, drugs targeting MTP are of interest as potential drugs for hyperlipidemia (a condition with elevated levels of lipid and/or lipoproteins).

Would there be an added benefit to combination therapy (MTP inhibitor plus statin) for patients who are heterozygous FH? In your answer, you do not need to consider the effect of statins on the regulation of HMG-CoA reductase.

Explanation / Answer

Statins are particularly well suited for lowering LDL, the cholesterol with the strongest links to vascular diseases. In studies using standard doses, statins have been found to lower LDL-C by 18% to 55%, depending on the specific statin being used. There is a risk of severe muscle damage myopathy and rhabdomyolsis with statins (AMDA) . Further, Statins may be less effective in reducing LDL cholesterol in people with FH as these people have defects usually in either the LDL receptor or apolipoprotein B genes, both of which are responsible for LDL clearance from the blood. Further as the microsomal triglyceride transfer protein (MTP) is essential for the hepatic secretion of apolipoprotein (apo) B-containing lipoproteins. MTP is rate-limiting for VLDL apoB secretion in wild-type mice under basal chow-fed conditions, (Tietge, 1999). Thus the added benefit to combination therapy (MTP inhibitor plus statin) for patients who are heterozygous FH is the fact that the: adverse side effects of both the drugs will be reduced as there will be smaller requirement of dosage of each drug in case of a combination therapy, apart from this due to the above mentioned fact that Statins may be less effective in reducing LDL cholesterol in people with FH as these people have defects usually in either the LDL receptor or apolipoprotein B genes, both of which are responsible for LDL clearance from the blood there is a need to complement this defect with another drug that acts on another pathway to lower the VLDL level. The risk of severe muscle damage myopathy and rhabdomyolsis with statins will be lowered incase of lower dosage of the drug due to combination therapy of (MTP) inhibitor.

Related Questions

Navigate

• Browse (All)
• Browse I
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.