List potential therapeutic approaches to controlling circulating cholesterol lev

Question

List potential therapeutic approaches to controlling circulating cholesterol levels (8marks)

Explain whether each approach listed above would be of potential benefit to an individual: (12 marks)

a.      Who produces defective LDL receptors

b.      Who has very high HMGCoA reductase activity

c.       Whose chylomicron remnant uptake mechanisms are defective

List potential therapeutic approaches to controlling circulating cholesterol levels (8marks)

Explain whether each approach listed above would be of potential benefit to an individual: (12 marks)

a.      Who produces defective LDL receptors

b.      Who has very high HMGCoA reductase activity

c.       Whose chylomicron remnant uptake mechanisms are defective

Explanation / Answer

In some recent studies, it has been proved that the LDL (Low-density lipoproteins) is the bad cholesterol which is the main reason for CVD ( cardiovascular disease). So for that, some therapeutic strategies are very effective for treating dyslipidemia and reduces the chance of CVD also. So those strategies are listed below:

1. PCSK9 protein targeting ( with the help of endogenous and exogenous modulations)

2. Antisense oligonucleotide (ASO) mediated targeting

3. HDL (high-density lipoprotein) targeting and reverse transport of cholesterol:

in previous studies, it has been suggested that LDL-C level is the reason of CVD but the HDL-C is inversely related with the CVD.

3.1 Inhibition of CETP: So in this therapy, inhibition of CETP (cholesterol ester transferase protein) leads to increase of HDL-C concentration in blood by reducing the transfer of cholesteryl ester from HDL to apoB (apolipoprotein B)-containing lipoproteins.

3.2 Uses of Niacin: Niacin has been used to reduce the CVD with the help of statins for increasing the level of HDL-C.

3.3 Infusion of recombinant HDL: Infusion of recombinant HDL enhances the RCT (reverse cholesterol transport) which leads to the reduction of plaque lipid volume or stabilization of vulnerable plaque.

3.4 Activation of LXR: ABCA1 and ABCG1 is the cholesterol transporter in macrophages, which are regulated by the LXR gene, so these help in regulation of the efflux of cholesterol from macrophages and it also help in regulation of RCT.

a. Genes which are affected by frameshift mutation & nonsense mutation causes the production of defective LDL receptor after translation.

b. When the blood sugar level rises and LDL-C concentration reses lead to increase the activity of HMG-CoA (3-hydroxy-3-methyl-glutaryl-coenzyme reductase).

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