April 11, 2013
Researchers Discover New Way To Cleanse The Blood Of Cholesterol
redOrbit Staff & Wire Reports - Your Universe Online
Researchers from the University of Michigan (UMich) have found a new genetic target which they believe could be used instead of -- or along with -- statins to help lower a person´s cholesterol.Scientists working in the lab of David Ginsburg at the Ann Arbor-based university´s Life Sciences Institute managed to inhibit the action of a gene responsible for transporting a protein known to interfere with the liver´s ability to remove cholesterol from the blood of mice.
Doing so essentially trapped the protein, making it impossible for it to hamper the receptors responsible for removing cholesterol. Essentially, it protected the capacity of the liver cells´ ability to remove plasma cholesterol from the blood, and it did so without causing other adverse health effects in the mice, the researchers said. Their findings were published in Monday´s edition of the online journal eLife.
According to a university news statement, the researchers “found that mice with an inactive SEC24A gene could develop normally. However, their plasma cholesterol levels were reduced by 45 percent because vesicles from liver cells were not able to recruit and transport a critical regulator of blood cholesterol levels called proprotein convertase subtilisin/kexin type 9. PCSK9 is a secretory protein that destroys the liver cells' receptors of low-density lipoprotein— LDL, the so-called ℠bad cholesterol´ — and prevents the cells from removing the LDL.”
Inhibiting either SEC24A or PCSK9 could be an alternative treatment to statins, or could work together with the medications to enhance the cholesterol-removing effects of the drugs, first author Xiao-Wei Chen explained.
Furthermore, this treatment method could be effective on patients who are intolerant of or resistant to statins, he added. Early studies of anti-PCSK9 therapies in humans have shown that they regulate and “dramatically” lower cholesterol, especially when paired with statins.
Chen and colleagues believe that future treatment options could block the transport mechanism that allows PCSK9 from reaching the LDL receptors rather than attempting to inhibit the secretory protein itself. “Without SEC24A, much of the PCSK9 couldn't make its way out of the cells to destroy the LDLR, which then clears cholesterol from the blood,” he explained.
By blocking the SEC24A gene, the researchers were able to keep PCSK9 trapped inside cells. This kept LDL receptors intact and allowed the liver to continue clearing cholesterol out of the body, thus preventing it to accumulate in arteries and lead to potential cardiovascular issues.
“We have no reason at this point to expect that this strategy will be any better than anti-PCSK9 therapy for treating high cholesterol, but it would be another alternative approach, and it's hard to predict which drugs will work the best and be the safest until we actually try them out in people,” said Ginsburg.
The research was funded by the Howard Hughes Medical Institute (HHMI), the National Institutes of Health (NIH) and the American Heart Association (AHA). Experts from the HHMI, the Cleveland Clinic, UC-Berkeley, UCLA and Wayne State University also contributed to the study.