Using nanoparticles to prevent heart attacks and strokes

Statins are drugs that have several effects, but are primarily known for decreasing cholesterol synthesis by the liver and decreasing the LDL (bad) cholesterol level in the blood.

Statins inhibit an enzyme that normally allows the liver to produce cholesterol. The statin also causes the liver cells to draw LDL out of the bloodstream.

But statins also work directly in blood vessels as outlined below. In arteries (like the coronary arteries that supply the heart), statins can decrease local inflammation, help keep plaque stable, decrease blood clot formation, and help protect the endothelial cells (cells that line the artery) in the vessel wall.

Photo courtesy of Mt. Sinai: "Mount Sinai's novel HDL nanoparticle (red), loaded with a statin drug, specifically targets and locally treats inflammatory macrophage cells (green) hiding inside high-risk plaque within blood vessels."

Photo courtesy of Mt. Sinai: “Mount Sinai’s novel HDL nanoparticle (red), loaded with a statin drug, specifically targets and locally treats inflammatory macrophage cells (green) hiding inside high-risk plaque within blood vessels.”

Over time, a complex series of events occurs in many arteries. These events can lead to heart attacks. A part of the artery wall (its endothelium), cholesterol, macrophages, chemical mediators, calcium and other components work to produce plaque. Plaque is a deposit that gradually builds up in the arteries. Sometimes plaque can rupture (crack) and the fractured surfaces can activate platelets leading to a blood clot. This clot blocks the artery and stops blood flow. The area of the heart that is deprived of blood begins to die. If the clot can be removed quickly, heart damage may not occur or be minimal.

Currently, the goal is to get rid of the clot as fast as possible using either a special type anticoagulant, or doing a somewhat limited surgical intervention and placing a stent.

A sizable number of patients who have a heart attack will have another heart attack relatively soon after the first. This happens because of inflammation – the inflammation that continues in the arteries. This can occur even when a patient is taking an oral statin. The statin, taken by mouth, will lower cholesterol levels, as described above, but has limited effect in the plaque-laden arteries themselves.

Researchers have come up with a possible solution using nanotechnology.

They’ve made HDL (good cholesterol) molecules that have a statin attached to them. Once the clot has been cleared, the HDL-statin complex is injected intravenously. The complex moves through the bloodstream and gets to the macrophages that are active in the plaque. The HDL binds in the area and the statin diffuses out. The local application of the statin significantly decreases inflammation in the area. And it helps to stabilize the remaining plaque. After the IV dose, the patient would continue on an oral statin to help keep LDL low to prevent future heart attacks.

So far this technique has only been used in mice, but it has shown promising results. If clinical studies in humans are successful, this HDL-statin complex may be a tool to help prevent a repeat heart attack after an initial one. Additionally, this same technique could also be used to help prevent strokes that can occur via a similar mechanism taking place in arteries that supply the brain.

And, perhaps, in the future, a dose of the nanoparticle can be given prophylactically, to prevent heart attacks and strokes in people who are at increased risk, but have no yet had one.  You can read more on the new technique here.

Mark Thoma, MD, is a physician who did his residency in internal medicine. Mark has a long history of social activism, and was an early technogeek, and science junkie, after evolving through his nerd phase. Favorite quote: “The most exciting phrase to hear in science... is not 'Eureka!' (I found it!) but 'That's funny.'” - Isaac Asimov

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