Caffeine Reduces PCSK9 Clears bad cholesterol and Prevents cardiovascular disease

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Caffeine Reduces PCSK9 Clears bad cholesterol and Prevents cardiovascular disease

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Caffeine Reduces PCSK9 Clears bad cholesterol and Prevents cardiovascular disease.

Molecular mechanism of drinking more coffee to prolong life: Caffeine reduces PCSK9, clears bad cholesterol, and prevents cardiovascular disease

Coffee , one of the most popular beverages worldwide,80% of adults drink at least one caffeinated beverage daily. According to statistics, the world consumes more than 9 billion kilograms of coffee every year.

Several past studies have also shown that regular coffee consumption can provide many health benefits, associated with a reduced risk of several cancers, including liver cancer, and a reduced risk of several chronic diseases.

Coffee contains a lot of caffeine , so many people drink it to boost their energy and productivity. There are also some large-scale studies that show that people who drink coffee and tea regularly have a lower risk of cardiovascular disease due to a higher intake of caffeine, which means that caffeine has a protective effect on the cardiovascular system, but until now, the specific The reason is still unclear.

Recently, researchers from McMaster University in Canada published a research paper entitled: Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance in the journal Nature Communications .

The study found and confirmed that caffeine can increase the level of calcium ions in the endoplasmic reticulum of hepatocytes, thereby blocking the activation of SREBP2 , thereby reducing the expression level of PCSK9 , increasing the expression of low-density lipoprotein receptor (LDLR) , and promoting low-density lipoprotein . Cholesterol (LDLc) clearance .

This finding provides a potential mechanism for the protective effects of caffeine on the cardiovascular system, and also helps in the development of drugs for the prevention and treatment of cardiovascular and other metabolic diseases.

Low-density lipoprotein cholesterol (LDLc), when it is excessive, will accumulate on the arterial wall, easily causing cardiovascular diseases such as arteriosclerosis. Therefore LDL cholesterol is also called ” bad cholesterol “.

The PSCK9 protein expressed by the PCSK9 gene can bind to and degrade the low-density lipoprotein receptor (LDLR) in liver cells , thereby increasing the level of low-density lipoprotein cholesterol (LDLc) in the blood.

Therefore, inhibiting the expression of PCSK9 gene or inhibiting the binding of PCSK9 protein to LDLR can reduce the level of LDLc, thereby preventing the occurrence of cardiovascular disease.

At present, there are small molecule drugs, monoclonal antibodies and siRNA drugs that target PCSK9 to reduce blood lipids and prevent and treat cardiovascular diseases.

There are also studies using gene editing technology to directly modify the PCSK9 gene to prevent cardiovascular disease once and for all.

In this study, the research team found that caffeine intake was associated with lower levels of PCSK9 in the blood and increased levels of LDLR in liver cells .

The PCSK9-lowering effect of caffeine was verified in a group of healthy human volunteers.

Further mechanism studies showed that caffeine increased the level of calcium ions in the endoplasmic reticulum of hepatocytes, thereby blocking the activation of SREBP2 , which in turn decreased the expression level of PCSK9, increased the expression of low-density lipoprotein receptor (LDLR) , and promoted low- density lipoprotein receptor (LDLR) expression. Clearance of density lipoprotein cholesterol (LDLc) .

In addition, the research team also developed several caffeine derivatives that better block SREBP2 and reduce PCSK9 levels.

Caffeine blocks PCSK9 expression and promotes LDLc clearance from hepatocytes

Overall, this study provides a potential mechanism by which coffee can reduce the risk of cardiovascular disease—caffeine increases low-density lipoprotein receptor (LDLR) expression by blocking SREBP2, reducing PC SK9 levels, and promoting low- density lipoprotein receptors (LDLR). Clearance of density lipoprotein cholesterol (LDLc) .

The findings, which combine a widely used drink with cholesterol metabolism, also suggest that the impact of diet on health is more complex than we thought.

The research team said that the new caffeine derivatives they developed could lower PCSK9 levels in the blood better than caffeine, thus opening up the possibility for the development of new drugs or nutritional products for lowering low-density lipoprotein cholesterol (LDLc) .

In addition, SREBP2 is implicated in many metabolic diseases, such as diabetes and fatty liver , so this finding may have other profound implications.

Reference:
https://www.nature.com/articles/s41467-022-28240-9

Caffeine Reduces PCSK9 Clears bad cholesterol and Prevents cardiovascular disease

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