7-Dehydrocholesterol but not cholesterol is important in the development of ASCVD

What is it about?

For decades, cholesterol has been thought to cause atherosclerotic cardiovascular disease (ASCVD). However, recent epidemiological studies do not support a relationship between dietary cholesterol and/or blood cholesterol and ASCVD. We provide the molecular evidence indicating that 7-dehydrocholesterol (7-DHC), but not cholesterol, is involved in the development of ASCVD. 7-DHC is the biosynthetic precursor of cholesterol. 7-DHC is only produced in the body and causes ASCVD after accumulation in tissues by suppressing the activity of TGF-β, a protective cytokine against ASCVD, in vascular endothelium. We suggest that TGF-β enhancers, such as statins, triterpenoids, polyphenols and antioxidants, are therapeutic agents for ASCVD. They counteract the 7-DHC-mediated suppression of TGF-β activity in aortic endothelium.

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Why is it important?

Our work provides molecular evidence that 7-DHC, but not cholesterol, causes ASCVD. This will lead to effective prevention and treatment of ASCVD using TGF-β enhancers. Our work may also provide the molecular mechanism and potentially effective treatments of the Smith-Lemli-Opitz syndrome (SLOS).

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