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Overview of coronary stents

October 10, 2017

The June issue of Mayo Clinic Health Letter offers an overview of this treatment, including an update on recent research that raised some questions about stent use.

In angioplasty, doctors insert a flexible tube (catheter) into a leg or arm and thread it toward a blocked heart artery. In the early days of this procedure, a balloon at the end of the catheter was inflated to stretch open the artery. About 30 to 40 percent of the time, the stretched vessel would narrow again. In the mid-1990s, the Food and Drug Administration approved the routine use of stents, which are expanded into place using balloon angioplasty and left within the artery to help keep it open. This procedure helps about 1 million Americans each year.

Recently, a large study suggested that angioplasty may not be necessary in people who have regular, predictable chest pain due to partially blocked arteries. However, if medication and lifestyle changes don't relieve pain, or if there is a change in the usual pattern of chest pain, stents may still be the best treatment.

Other research found an increased risk of blood clots in the newest type of stents, called drug-eluting stents. These devices are coated with a drug that is released over about 30 days to inhibit inflammation and scar tissue growth. This risk is low when patients take recommended medications.

Stents aren't risk free, but they've allowed millions of Americans to avoid far more extensive heart bypass surgery to open critical blockages in arteries leading to the heart. For patients without other significant risk factors, the risk of major complications related to angioplasty - such as heart attack, death or stroke - is less than 3 percent.

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The result was the drug known as BMS309403, described in the Nature article as a "rationally designed, potent, and selective inhibitor of aP2" that blocks the protein's ability to bind with fatty acids -- the function that leads to inflammatory and metabolic havoc when a high-fat or high-cholesterol diet is consumed. The drug appears to have no effect on lean animals eating a normal diet, the scientists said, suggesting that blocking aP2 may not be harmful in people -- though this remains to be determined.

The report describes tests of the inhibitor on cell systems in culture and in live mice. In one experiment, mice genetically engineered to be highly susceptible to atherosclerosis were fed high-fat diets and assigned to receive the drug or an inert substance. One set of mice was put on a high-fat "western" diet at five weeks of age; half received the inhibitor drug. A second group of animals ate the western diet for eight weeks, at which time they developed severe atherosclerosis. Then they were started on the drug to determine whether the drug could halt or reverse the disease process.

In both experiments, the drug treatment reduced the size of fatty plaques in the animals' aortas by more than 50 percent compared to control mice.

To study the impact of the aP2 inhibitor on diabetes, the scientists used a genetic animal model of obesity and insulin resistance, as well as normal mice fed a diabetes-inducing diet.

In both animal models, the mice that received the inhibitor drug were found to have lower blood sugar and triglycerides -- a component of "bad" cholesterol -- and significantly improved insulin sensitivity compared to control mice. Tests also showed that the drug reduced the activity of gene pathway called JNK that triggers the inflammatory and insulin-resistance responses to fatty diets.

As an "added bonus," commented Hotamisligil, the drug also exerted a marked protective effect against another metabolic disorder, fatty liver disease.

While the genetic variant studies in humans indicate that a drug like the one used in the current experiments is likely to work in humans, Hotamisligil said that this remains to be proven. The next step is to perform more detailed toxicity tests in animals, and then move toward human testing.

The important lesson from the new study, the researchers wrote in their report, is the demonstration that aP2 can be blocked by a small-molecule, oral compound. In turn, they add, the results suggest that targeting aP2 "can lead to a new class of powerful therapeutic agents to prevent and treat metabolic diseases such as type 2 diabetes and atherosclerosis."

Said Hotamisligil, "This work turned out to be a perfect example of out-of-the box thinking, inter-institutional and inter-disciplinary science, to bridge discovery with application and fruitful industry-academia collaboration."

hsph.harvard