Most of us are familiar with “good” and “bad” cholesterol. Low-density lipoprotein (LDL) is “bad” because it keeps cholesterol in the body, while the “goodness” of high-density lipoprotein (HDL) stems from its ability to scoop up old, used cholesterol and escort it to the liver for disposal. Because high levels of HDL in the blood are associated with lower risk of cardiovascular disease (a link that has recently come under question), it has received much attention from researchers.
And anyone who travels a great deal has probably heard about deep vein thrombosis or DVT, often cited as a good reason to get up and stretch your legs on a long flight. Restriction of normal blood flow—whether from being bedridden, paralyzed or sitting for hours on airplanes—is a major cause of blood clots in the legs. Though these clots can be painful in and of themselves, if they break free and travel to the lungs they can cause a potentially fatal pulmonary embolism. In fact, DVTs afflict nearly a million Americans each year and claim a quarter of a million lives.
Now a team from the lab of Denisa Wagner, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine and the Immune Disease Institute (PCMM/IDI), directed by Alexander Brill, MD, PhD, has found a connection between “good” cholesterol and DVT that may change the way these dangerous clots are treated—and perhaps prevented.
There are a couple of ways for the body to remove cholesterol. One, selective lipid uptake, relies on an HDL receptor called SR-BI and molecules called apolipoproteins to transfer HDL to the liver.
Using a mouse model that mimics restriction of blood flow (one of the main causes of DVTs in humans), Wagner’s team showed that mice genetically engineered to lack SR-BI—which have higher cholesterol and abnormal HDL—were more likely to develop DVT, suggesting that SR-BI plays a protective role against clots.
Mice were also more likely to form clots if they lacked a major building block of HDL called apoA-I or an enzyme involved in dilating blood vessels called eNOS (endothelial nitric oxide synthase, another target of SR-BI). When the missing apoA-I was supplied, the tendency to form clots disappeared.
Together, the results clarify that the trio of HDL (in the form of apoA-I), SR-BI and eNOS provides strong protection against DVT. More generally, they suggest that HDL plays a broad and important protective role in the circulatory system beyond what we already know about its salutary effects on heart health.
In practical terms, this three-part relationship between HDL, SR-BI and eNOS may offer new opportunities for both treatment and prevention of DVT in humans. For example, a compound that mimics apoA-I activity or stimulates SR-BI could help protect at-risk individuals from life-threatening deep vein clots—whether they’re the result of being confined to bed, suffering paralysis, or spending many hours on a long transatlantic flight.
Paul Guttry is an experienced medical editor and writer who has worked with researchers and clinicians in the Longwood Medical Area of Boston since 1999. His current clients include Brigham and Women’s Hospital, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston Children’s Hospital, the Harvard School of Public Health and Harvard Business School.