Cholesterol Metabolism and Vascular Disease


Cholesterol is packaged into lipoprotein particles in the liver and intestine and transported to peripheral tissues for normal cellular function. Reverse cholesterol transport is the mechanism by which excess cholesterol is transported back to the liver and is facilitated by high‐density lipoproteins (HDLs). Increased plasma concentrations of cholesterol within the low‐density lipoprotein (LDL) molecule contribute to atherosclerotic vascular disease that commonly affects the coronary, cerebral and peripheral vascular circulation.

There is now strong evidence to support the use of the statin class of drugs to decrease the risk of cardiovascular disease. Statins inhibit hepatic cholesterol synthesis, increase hepatic low‐density lipoprotein cholesterol (LDLc) receptor expression and consequently decrease plasma LDLc, to reduce the risk of myocardial infarction in people at widely varying risk of heart disease. At present, there is limited evidence to support the use of alternative classes of lipid‐lowering medications to reduce the risk of cardiovascular disease. Clinical trials are currently ongoing to assess the safety and efficacy of new types of medications to treat dyslipidaemias, the most promising of which are targeted against proprotein convertase subtilysin kexin 9 (PCSK9).

Key Concepts

  • Endogenous and exogenous lipid pathways exist within the body.
  • There are both inherited and acquired forms of hypercholesterolaemia.
  • Low‐density lipoprotein cholesterol (LDLc) is associated with the development of coronary heart disease.
  • Disordered lipid metabolism plays a crucial role in the development of atherosclerotic vascular disease.
  • There is much clinical trial evidence now showing the effectiveness of certain classes of lipid‐lowering medication in lowering cholesterol levels and reducing the risk of cardiovascular disease.

Keywords: hypercholesterolaemia; atherosclerotic vascular disease; lipid‐lowering medication; clinical trials; cardiovascular risk

Figure 1. Relationship among dietary nutrients, lipid synthesis, lipoproteins and atherosclerotic disease.
Figure 2. Relationship between various lipoprotein transport pathways.


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Further Reading

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Rader DJ and Hovingh GK (2014) HDL and cardiovascular disease. Lancet 384 (9943): 618–625.

Ridker PM (2014) LDL cholesterol: controversies and future therapeutic directions. Lancet 384 (9943): 607–617.

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Wainwright, Patrick, Ryan, Aidan, Olufadi, Rasaq, and Byrne, Christopher D(Nov 2015) Cholesterol Metabolism and Vascular Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002264.pub3]