Gene editing technology could boost accuracy of predicting heart disease risk

Scientists may have the power to assess whether carrying a specific genetic variant increases a person's risk for disease using gene editing and stem cell technologies. An article titled "Determining the pathogenicity of a genomic variant of uncertain significance using CRISPR/Cas9 and human-induced pluripotent stem cells," in the journal Circulation June 18, 2018, details a study that demonstrates the potential of combining stem cell-based disease modeling and CRISPR/Cas9-mediated genome editing technology as a personalized risk-assessment platform for determining the disease-causing ability of a variant of uncertain significance. Researchers studied genetic variants associated with hypertrophic cardiomyopathy, a common cause of sudden cardiac death in young people and athletes. They harvested DNA from 54 healthy or symptom-free individuals without heart disease. Next, they sequenced the DNA using a custom panel of 135 cardiomyopathy and congenital heart disease genes associated with sudden cardiac death. The sequence results uncovered 592 unique genetic variants, with 78 percent of genetic variants being classified as "benign," "likely benign," or a "variant of uncertain significance." However, 17 were annotated as "likely pathogenic" or disease-causing. "Given the diversity of the human genome[,] . . . it is difficult to determine whether a genetic "variant" is meaningful or not. As a result, we risk treating patients with medications or more for a variant that, in the end, is benign," said Circulation editor Joseph Hill, chief of cardiology at the University of Texas Southwestern Medical Center in Dallas. "This approach heralds a new era of in vitro disease modeling and drug testing as pivotal elements of precision medicine."

Halting progression to heart failure

Researchers are eyeing the potential of the Therepi device to halt the progression from heart attack to heart failure. The device contains a reservoir that attaches directly to the damaged heart tissue. A refill line connects the reservoir to a port on or under the patient's skin, where therapies can be injected either by the patient or a health care professional. A new study published in Nature Biomedical Engineering details how Therepi can be used to restore cardiac function as it aims to address the problems with current drug delivery methods. The device's reservoir, which is constructed from a gelatin-based polymer, can be implanted in a single procedure. In addition, the reservoir permits the administration of stem cell therapies. In a rat model, the device proved effective in improving cardiac function after a heart attack. The research was published June 11, 2018, in an article titled "Sustained release of targeted cardiac therapy with a replenishable implanted epicardial reservoir."

Time for a salad?

Sensitivity to an allergen in red meat could lead to the buildup of plaque in the arteries of the heart, according to researchers. A study looking into this potential link appeared in Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), a journal of the American Heart Association. While the exact number of people in the U.S. with this allergy is unknown, the researchers said it could reach 1 percent in some areas. Further, the number of people who develop blood antibodies to the red meat allergen without having full-blown symptoms could be as much as 20 percent of the population in some areas, the researchers added. Scientists only recently identified the main allergen in red meat, which is galactose-α-1,3-galactose, or alpha-Gal, a type of complex sugar. The Lone Star tick sensitizes people to this allergen through its bite. These ticks are more prevalent in the southeastern U.S., but have been seen in Long Island, N.Y. "This novel finding from a small group of subjects from Virginia raises the intriguing possibility that allergy to red meat may be an under recognized factor in heart disease," said study leader Coleen McNamara, a professor of medicine in the Cardiovascular Research Center of the University of Virginia Health System, Charlottesville. "These preliminary findings underscore the need for further clinical studies in larger populations from diverse geographic regions and additional laboratory work." The findings appeared in an article titled "IgE to the mammalian oligosaccharide Galactose-α-1,3-Galactose is associated with increased atheroma volume and plaques with unstable characteristics," published June 14, 2018.

ED raises risk for heart problems

Researchers have found that men with erectile dysfunction (ED) are at greater risk for heart attacks, strokes and sudden cardiac death. Their findings, published in the journal Circulation, are based on the experiences of more than 1,900 men between 60 to 78 years of age. ED affects about 20 percent of men 20 years of age and older, according to research. Cardiovascular disease and ED share common risk factors, including obesity, hypertension, smoking, diabetes and metabolic syndrome. During a four-year follow-up, there were a total of 115 fatal and nonfatal heart attacks, fatal and nonfatal strokes, cardiac arrests and sudden cardiac deaths. A greater proportion of men who reported ED (6.3 percent) suffered heart attacks, cardiac arrests or strokes than men who did not report ED (2.6 percent). When the investigators adjusted their analysis to eliminate the potential influence of other risk factors, they found that men with ED were about twice as likely to suffer cardiovascular events than men without the condition. The findings, the research team says, suggest that ED as an indicator can help physicians gauge cardiovascular risk among middle-aged men. Participants are part of the ongoing Multi-Ethnic Study of Atherosclerosis, which is following more than 6,000 people of various ethnic and racial backgrounds at several cities across the U.S. The findings were reported in an article published June 11, 2018, titled "Erectile dysfunction as an independent predictor of future cardiovascular events: the multi-ethnic study of atherosclerosis."

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