cardiovascular disease
Precision Medicine: Using Genomic Data to Predict Drug Side Effects and Benefits
People with type 2 diabetes are at increased risk for heart attacks, stroke, and other forms of cardiovascular disease, and at an earlier age than other people. Several years ago, the Food and Drug Administration (FDA) recommended that drug developers take special care to show that potential drugs to treat diabetes don’t adversely affect the cardiovascular system [1]. The challenge in implementing that laudable exhortation is that a drug’s long-term health risks may not become clear until thousands or even tens of thousands of people have received it over the course of many years, sometimes even decades.
Now, a large international study, partly funded by NIH, offers some good news: proof-of-principle that “Big Data” tools can help to identify a drug’s potential side effects much earlier in the drug development process [2]. The study, which analyzed vast troves of genomic and clinical data collected over many years from more than 50,000 people with and without diabetes, indicates that anti-diabetes therapies that lower glucose by targeting the product of a specific gene, called GLP1R, are unlikely to boost the risk of cardiovascular disease. In fact, the evidence suggests that such drugs might even offer some protection against heart disease.
Tags: anti-diabetes drugs, big data, cardiovascular disease, diabetes, diabetic heart disease, drug benefits, drug development, drug side effects, drug targets, genetic variant, genomics, GlaxoSmithKline, GLP1R, heart disease, investigational drugs, liraglutide, Mendelian randomization, PMI, precision medicine, Precision Medicine Initiative cohort, T2D, type 2 diabetes, Victoza
Bioengineering: Big Potential in Tiny 3D Heart Chambers
Caption: Heart microchamber generated from human iPS cells; cardiomyocytes (red), myofibroblasts (green), cell nuclei (blue)
Credit: Zhen Ma, University of California, Berkeley
The adult human heart is about the size of a large fist, divided into four chambers that beat in precise harmony about 100,000 times a day to circulate blood throughout the body. That’s a very dynamic system, and also a very challenging one to study in real-time in the lab. Understanding how the heart forms within developing human embryos is another formidable challenge. So, you can see why researchers are excited by the creation of tiny, 3D heart chambers with the ability to exist (see image above) and even beat (see video below) in a lab dish, or as scientists say “in vitro.”
Credit: Zhen Ma et al., Nature Communications
To achieve this feat, an NIH-funded team from University of California, Berkeley, and Gladstone Institute of Cardiovascular Disease, San Francisco turned to human induced pluripotent stem (iPS) cell technology. The resulting heart chambers may be miniscule—measuring no more than a couple of hair-widths across—but they hold huge potential for everything from improving understanding of cardiac development to speeding drug toxicity screening.
Tags: bioengineering, birth defects, cardiology, cardiovascular disease, congenital heart defects, drug screening, geometric confinement, heart, heart chamber, heart development, induced Pluripotent Stem cells, iPS cells, microchambers, organs on a chip, pericardium, thalidomide, Tissue Chip for Drug Screening Program, tissue chips
Blood Sugar Control for Diabetes: Asking the Heart Questions
Credit: Thinkstock
When most people think about risk factors for cardiovascular disease, they likely think of blood pressure readings or cholesterol levels. But here’s something else that should be high on that list: diabetes. That’s because people with diabetes are roughly twice as likely to die of heart disease than other folks [1]. Yet the issue of how best to help such people lower their cardiovascular risks remains a matter of intense debate. Some studies have suggested that part of the answer may lie in tightly controlling blood sugar (glucose) levels with a strict regimen of medications and monitoring [2]. Other research has shown that the intense effort needed to keep blood glucose levels under tight control might not be worth it and may even make things worse for certain individuals [3].
Now, a follow up of a large, clinical trial involving nearly 1,800 U.S. military veterans with type 2 diabetes—the most common form of diabetes—provides further evidence that tight blood glucose control may indeed protect the cardiovascular system. Reporting in The New England Journal of Medicine [4], researchers found a significant reduction in a composite measure of heart attacks, strokes, heart failure, and circulation-related amputations among the vets who maintained tight glucose control for about five and a half years on average. What’s particularly encouraging is most of the cardiovascular-protective benefit appears to be achievable through relatively modest, rather than super strict, reductions in blood glucose levels.
Tags: blood glucose levels, blood sugar, cardiovascular disease, diabetes, glimepiride, heart disease, hemoglobin A1C, insulin, metformin, precision medicine, Precision Medicine Initiative, rosiglitazone, type 2 diabetes, Veterans Affairs Diabetes Trial
Nanoparticles Target Damaged Blood Vessels
Caption: [A] Elastin stain (black) showing damaged elastic lamina in aorta. Inset (higher magnification) shows fluorescent nanoparticles attached to aorta where elastin is damaged. [B] Elastin stain showing aorta with undamaged elastic lamina. Inset shows no nanoparticle attachment. L stands for lumen, the open area inside the aorta.
Credit: Naren Vyavahare, Clemson University
Posted In: Science
Tags: antibody, blood vessels, cardiovascular disease, CVD, drug delivery, elastic lamina, nanoparticles, stents
MicroRNA Research Takes Aim at Cholesterol
Caption: Illustration of artery partially blocked by a cholesterol plaque.
If you’re concerned about your cardiovascular health, you’re probably familiar with “good” and “bad” cholesterol: high-density lipoprotein (HDL) and its evil counterpart, low-density lipoprotein (LDL). Too much LDL floating around in your blood causes problems by sticking to the artery walls, narrowing the passage and raising risk of a stroke or heart attack. Statins work to lower LDL. HDL, on the other hand, cruises through your arteries scavenging excess cholesterol and returning it to the liver, where it’s broken down.
Posted In: Science
Tags: ABCA1, cardiovascular disease, cholesterol, diabetes, HDL, high-density lipoprotein, LDL, lipids, low-density lipoprotein, MicroRNA, miR-27b, miR-33a, miR-33b, miRNA, National Institutes of Health, NIH, protein, ribonucleic acid, RNA, stroke
